Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague Dawley rats were first trained on the RAWM and subsequently trained on FMI. Following acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when food reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing precision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher’s r to z transformation revealed no significant differences between control and stress with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been direct compared within the same animals following chronic stress, using FMI, an appetitive task, and RAWM, a non-appetitive task.
Impulsivity; Reference Memory; Radial arm water maze; fixed minimum interval; rat
The anterior thalamus (AT) is anatomically interconnected with the hippocampus and other structures known to be involved in memory, and the AT is involved in many of the same learning and memory functions as the hippocampus. For example, like the hippocampus, the AT is involved in spatial cognition and episodic memory. The hippocampus also has a well-documented role in contextual memory processes, but it is not known whether the AT is similarly involved in contextual memory. In the present study, we assessed the role of the AT in contextual memory processes by temporarily inactivating the AT and training rats on a recently developed context-based olfactory list learning task, which was designed to assess the use of contextual information to resolve interference. Rats were trained on one list of odor discrimination problems, followed by training on a second list in either the same context or a different context. In order to induce interference, some of the odors appeared on both lists with their predictive value reversed. Control rats that learned the two lists in different contexts performed significantly better than rats that learned the two lists in the same context. However, AT lesions completely abolished this contextual learning advantage, a result that is very similar to the effects of hippocampal inactivation. These findings demonstrate that the AT, like the hippocampus, is involved in contextual memory and suggest that the hippocampus and AT are part of a functional circuit involved in contextual memory.
anterior thalamus; learning; memory; interference; context
Consistent with a popular theory of associative learning, the Pearce-Hall (1980) model, the surprising omission of expected events enhances cue associability (the ease with which a cue may enter into new associations), across a wide variety of behavioral training procedures. Furthermore, previous experiments from this laboratory showed that these enhancements are absent in rats with impaired function of the amygdala central nucleus (CeA). A notable exception to these assertions is found in feature negative (FN) discrimination learning, in which a “target” stimulus is reinforced when it is presented alone but nonreinforced when it is presented in compound with another, “feature” stimulus. According to the Pearce-Hall model, reinforcer omission on compound trials should enhance the associability of the feature relative to control training conditions. However, prior experiments have shown no evidence that CeA lesions affect FN discrimination learning. Here we explored this apparent contradiction by evaluating the hypothesis that the surprising omission of an event confers enhanced associability on a cue only if that cue itself generates the disconfirmed prediction. Thus, in a FN discrimination, the surprising omission of the reinforcer on compound trials would enhance the associability of the target stimulus but not that of the feature. Our data confirmed this hypothesis, and showed this enhancement to depend on intact CeA function, as in other procedures. The results are consistent with modern reformulations of both cue and reward processing theories that assign roles for both individual and aggregate error terms in associative learning.
attention; associability; associative learning; feature negative discrimination; amygdala
Drug-associated cues are believed to be important mediators of addiction and drug relapse. Although such cues may influence drug-seeking behavior through multiple routes, it is their putative incentive motivational properties – their ability to elicit “craving” – that interests many addiction researchers. The Pavlovian-to-instrumental transfer paradigm is commonly used to assay cue-evoked incentive motivation in situations involving natural rewards, but has not been widely applied to the study of drug self-administration. We used this paradigm to determine if cues paired with intravenous cocaine could promote performance of an independently trained task in which rats self-administered cocaine by completing a chain of two different lever press actions, a procedure used to parse behavior into cocaine-seeking (first action) and cocaine-taking (second action). Rats showed significant transfer, increasing task performance during cocaine-paired cues. This effect was observed for both seeking and taking actions, although a trend towards greater cocaine taking was observed, a result that is consistent with studies using natural rewards. Our results demonstrate that cocaine-paired cues can provoke the pursuit of cocaine through a Pavlovian motivational process. This phenomenon may provide a useful new tool for modeling drug relapse, particularly as a method for targeting the response-invigorating effects of stimulus-drug learning.
Pavlovian instrumental transfer; cocaine; self-administration; seeking taking chain; addiction
Previous work has demonstrated that injections of the γ-aminobutyric acidA (GABAA) agonist muscimol into the nucleus accumbens shell (AcbSh) induce pronounced increases in the intake of solid foods and sucrose solutions, but do not potentiate water intake. In order to clarify the range of situations in which inactivation of the AcbSh potentiates ingestive behavior, we examined the effects of muscimol injections on the intake of a 3% NaCl solution in sodium-depleted animals. Although sodium-depleted subjects avidly consumed this solution, muscimol injections had no effect either on the volume consumed or on a variety of microstructural licking parameters. In contrast, in these same animals, muscimol injections significantly increased licking of a 10% sucrose solution. These results suggest that inactivation of the AcbSh may selectively increase the intake of foods, but not that of other homeostatically relevant ingestates. Examination of microstructural parameters suggested that the effect of muscimol on sucrose intake was not mediated by alterations in the “palatability” of the sucrose solution. We also observed that sodium-depleted subjects displayed significantly larger salt intakes after their second experience with sodium depletion than their first, and microstructural analysis in this case indicated that this sensitization effect was produced in a manner consistent with the animals showing increased “hedonic responsiveness” to the salt solution.
ventral striatum; ingestive behavior; sodium hunger; sodium appetite; blood chemistry
Neuromodulatory systems such as noradrenaline (NE), acetylcholine (ACh) and serotonin (5HT) serve important functions in sensory perception. We use the olfactory bulb (OB) as a model system to study the roles of individual neuromodulators in sensory perception. Using a spontaneous, non-reward motivated detection task, as well as a reward-motivated task, we show that rats can easily respond to odorants at very low concentrations when motivated to do so in a food rewarded task, despite not showing spontaneous responses to these low concentration odorants. Using the same tasks paired with local bulbar infusions of noradrenergic and cholinergic drugs, we then show that rats engage their noradrenergic, but not their cholinergic system to better respond to near threshold odorants. These results suggest that while cholinergic modulation of OB function is mostly important for odor decorrelation and discrimination, noradrenergic modulation is important for signal-to-noise modulation.
Olfaction; neuromodulation; olfactory bulb; noradrenaline; acetylcholine
Adolescence is an ontogenetic period characterized by numerous hormonal, neural, and behavioral changes. In animal models, adolescents exhibit greater levels of novelty-seeking behavior and risk-taking relative to adults, behaviors associated in humans with increases in impulsivity and elevated propensities to engage in drug and alcohol seeking behaviors. The current series of experiments sought to explore possible age-related differences in impulsivity when indexed using delay discounting in adolescent (postnatal day [P] 25-27) and adult (P68-71) female (Experiment 1) and male (Experiment 2) Sprague-Dawley rats. In both experiments, adolescents exhibited significantly greater levels of impulsive-like behavior in this test relative to adults—even when data were adjusted to account for baseline differences in activity levels (i.e. general nose-poking behavior) across age. Taken together, these results extend to both sexes previous findings of adolescent-associated elevations in impulsivity observed among male mice using delay discounting, as well as among male rats using other procedures to index impulsivity. That these age differences were observed among both male and female rats suggests that impulsivity may be a pervasive feature of adolescence, and contributes to the expression of risky behaviors during this ontogenetic period.
Adolescence; Rat; Impulsivity; Delay Discounting; Sex differences
There is growing evidence of heterogeneity among responses to bitter stimuli at the peripheral, central and behavioral levels. For instance, the glossopharyngeal (GL) nerve and neurons receiving its projections are more responsive to bitter stimuli than the chorda tympani (CT) nerve, and this is particularly true for some bitter stimuli like PROP & cycloheximide that stimulate the GL to a far greater extent. Given this information, we hypothesized that cutting the GL would have a greater effect on behavioral avoidance of cycloheximide and PROP than quinine and denatonium, which also stimulate the CT, albeit to a lesser degree than salts and acids. Forty male SD rats were divided into 4 surgery groups: bilateral GL transection (GLX), chorda tympani transection (CTX), SHAM surgery, and combined transection (CTX + GLX). Post-surgical avoidance functions were generated for the 4 bitter stimuli using a brief-access test. GLX significantly compromised avoidance compared to both CTX and SHAM groups for all stimuli (p < .02), while CTX and SHAM groups did not differ. Contrary to our hypothesis, GLX had a greater effect on quinine than cycloheximide (mean shift of 1.02 vs. 0.27 log10 units). Moreover, combined CTX + GLX transection shifted the concentration-response function further than GLX alone for every stimulus except cycloheximide (p’s < .03), suggesting that the GSP nerve is capable of maintaining avoidance of this stimulus to a large degree. This hypothesis is supported by reports of cycloheximide-responsive cells with GSP-innervated receptive fields in the NST and PBN.
bitter; glossopharyngeal; taste; GSP; brief-access test
Although the temporal characteristics of neural responses have been proposed as a mechanism for sensory neural coding, there has been little evidence thus far that this type of information is actually used by the nervous system. Here the authors show that patterned electrical pulses trains that mimic the response to the taste of quinine can produce a bitterlike sensation when delivered to the nucleus tractus solitarius of behaving rats. Following conditioned aversion training using either “quinine simulation” patterns of electrical stimulation or natural quinine (0.1 mM) as a conditioned stimulus, rats specifically generalized the aversion to 2 bitter tastants: quinine and urea. Randomization of the quinine simulation patterns resulted in generalization patterns that resembled those to a perithreshold concentration (0.01 mM) of quinine. These data provide strong evidence that the temporal pattern of brainstem activity may convey information about taste quality and underscore the functional significance of temporal coding.
taste; temporal coding; nucleus of the solitary tract; conditioned taste aversion; electrical brain stimulation
Fear conditioning studies have demonstrated the critical role played by the amygdala in emotion processing. Although all lesion studies until now investigated the effect of adult-onset damage on fear conditioning, the current study assessed fear-learning abilities, as measured by fear-potentiated startle, in adult monkeys that had received neonatal neurotoxic amygdala damage or sham-operations. After fear acquisition, their abilities to learn and use a safety cue to modulate their fear to the conditioned cue, and, finally, to extinguish their response to the fear conditioned cue were measured with the AX+/BX− Paradigm. Neonatal amygdala damage retarded, but did not completely abolish, the acquisition of a learned fear. After acquisition of the fear signal, four of the six animals with neonatal amygdala lesions discriminated between the fear and safety cues and were also able to use the safety signal to reduce the potentiated-startle response and to extinguish the fear response when the air-blast was absent. In conclusion, the present results support the critical contribution of the amygdala during the early phases of fear conditioning that leads to quick, robust responses to potentially threatening stimuli, a highly adaptive process across all species and likely to be present in early infancy. The neonatal amygdala lesions also indicated the presence of amygdala-independent alternate pathways that are capable to support fear learning in the absence of a functional amygdala. This parallel processing of fear responses within these alternate pathways was also sufficient to support the ability to flexibly modulate the magnitude of the fear responses.
safety-signal learning; post-traumatic stress disorder; emotion regulation; rhesus monkey
Fear-potentiated startle is defined as an increase in the magnitude of the startle reflex in the presence of a stimulus that was previously paired with an aversive event. It has been proposed that a subject’s awareness of the contingencies in the experiment may affect fear-potentiated startle. The authors adapted a conditional discrimination procedure (AX+/BX−), previously validated in animals, to a human fear-potentiated startle paradigm in 50 healthy volunteers. This paradigm allows for an assessment of fear-potentiated startle during threat conditions as well as inhibition of fear-potentiated startle during safety conditions. A response keypad was used to assess contingency awareness on a trial-by-trial basis. Both aware and unaware subjects showed fear-potentiated startle. However, awareness was related to stimulus discrimination and fear inhibition.
human startle response; contingency awareness; discrimination learning; fear inhibition
This study describes a novel spatial memory paradigm for monkeys and reports the effects of neonatal damage to the hippocampus on performance in adulthood. Monkeys were trained to forage in eight boxes hung on the walls of a large enclosure. Each box contained a different food item that varied in its intrinsic reward value, as determined from food preference testing. Monkeys were trained on a spatial and a cued version of the task. In the spatial task, the boxes looked identical and remained fixed in location whereas in the cued task, the boxes were individuated with colored plaques and changed location on each trial. Ten adult Rhesus macaques (5 neonatal sham-operated and 5 with neonatal neurotoxic hippocampal lesions) were allowed to forage once daily until they preferentially visited boxes containing preferred foods. The data suggest that all monkeys learned to discriminate preferred from nonpreferred food locations, but that monkeys with neonatal hippocampal damage committed significantly more working memory errors than controls in both tasks. Furthermore, following selective satiation, controls altered their foraging pattern to avoid the satiated food, whereas lesioned animals did not, suggesting that neonatal hippocampal lesions prohibit learning of specific food-place associations. We conclude that whereas an intact hippocampus is necessary to form specific item-in-place associations, in its absence, cortical areas may support more broad distinctions between food types that allow monkeys to discriminate places containing highly preferred foods.
monkey; hippocampus; spatial; memory; episodic
Supplemental choline during early stages of development can result in long-lasting improvements to memory function. In addition, pre- or postnatal choline has been shown to be protective against some of the adverse effects of early alcohol exposure. The present experiment examined whether supplemental choline given to rats would protect against the effects of post-training alcohol administration on trace fear conditioning. Post-training alcohol exposure in adolescent rats results in poor performance in this hippocampus-dependent task, although delay conditioning is unaffected. Here, rats were given an s.c. injection of either saline or choline chloride daily on postnatal days (PD) 15-26. On PD 30 subjects were trained in a trace fear conditioning procedure. For the next three days animals were administered 2.5 g/kg ethanol or water control, and CS-elicited freezing was measured on PD 34. Results indicated that post-training alcohol disrupted the expression of trace conditioning and that supplemental choline on PD 15-26 was protective against this effect. That is, choline-treated animals subsequently given post-training ethanol performed as well as animals not given ethanol. These results indicate that supplemental choline given during the periweaning period protects against ethanol-induced impairments in a hippocampus-dependent learning task. Findings contribute to the growing literature showing improvements in learning and memory in subjects given extra dietary choline during critical periods of brain development.
choline; hippocampus; frontal cortex; fear conditioning; alcohol; adolescence
Substance abuse and addiction are associated with an apparent devaluation of, and inattention to, natural rewards. This consequence of addiction can be modeled using a reward comparison paradigm where rats avoid intake of a palatable taste cue that comes to predict access to a drug of abuse. Evidence suggests rats avoid intake following such pairings, at least in part, because the taste cue pales in comparison to the highly rewarding drug expected in the near future. In accordance, lesions of the gustatory thalamus or cortex eliminate avoidance of a taste cue when paired with either a drug of abuse or a rewarding sucrose solution, but not when paired with the aversive agent, LiCl. The present study used bilateral ibotenic acid lesions to evaluate the role of a neighboring thalamic structure, the trigeminal orosensory area (TOA), in avoidance of a gustatory cue when paired with sucrose (Experiment 1), morphine (Experiment 2), cocaine (Experiment 3), or LiCl (Experiment 4). The results show that the TOA lesion disrupts, but does not eliminate avoidance of a taste cue that predicts access to a preferred sucrose solution and leaves intact the development of a LiCl-induced conditioned taste aversion. The lesion does, however, eliminate the suppression of intake of a taste cue when paired with experimenter administered morphine or cocaine using our standard parameters. As such, this is the first manipulation found to dissociate avoidance of a taste cue when mediated by a sweet or by a drug of abuse.
Trigeminal; Thalamus; Ibotenic Acid Lesion; Contrast; Reward Comparison
The medial preoptic area (MPOA) is an integral site for male sexual behavior. Dopamine is released in the MPOA before and during copulation and facilitates male rat sexual behavior. Repeated sexual experience and noncopulatory exposures to an estrous female facilitate subsequent copulation. However, the neurobiological mechanisms that mediate such enhancement remain unclear. Here, we examined the role of dopamine D1 receptors in the MPOA in experience-induced enhancement of male sexual behavior in rats. In Experiment 1, microinjections of the D1 antagonist SCH-23390 into the MPOA before each of 7 daily 30-min noncopulatory exposures to a receptive female impaired copulation on a drug-free test on day 8, compared to vehicle-treated female-exposed animals. Copulatory performance in drug-treated animals was similar to vehicle-treated males that had not been pre-exposed to females. This effect was site specific. There were no group differences in locomotor activity in an open field on the copulation test day. In Experiment 2, a separate cohort of animals was used to examine phosphorylation of dopamine-and cAMP-regulated phosphoprotein (DARPP-32) in the MPOA of animals with acute and/or chronic sexual experience. DARPP-32 is a downstream marker of D1 receptor signaling and substrate of cAMP-dependent protein kinase (PKA). Western immunoblot analysis revealed that p-DARPP-32 expression was greatest in the MPOA of males that received both acute and chronic sexual experience, compared to all other mated conditions and naïve controls. These data suggest that D1 receptors in the MPOA contribute to experience-induced enhancement of male sexual behavior, perhaps through a PKA regulated mechanism.
sexual behavior; medial preoptic area; D1 receptor; SCH-23390; DARPP-32
Previous research indicates that serotonin enhances the development of stress-induced changes in behavior, although it is unclear which serotonin receptors mediate this effect. 5-HT2 receptors are potential candidates because activation at these receptors is associated with increased fear and anxiety. In this study we investigated whether pharmacological treatments targeting 5-HT2 receptors would alter the acquisition and expression of conditioned defeat. Conditioned defeat is a social defeat model in Syrian hamsters in which individuals display increased submissive and defensive behavior and a loss of territorial aggression when tested with a novel intruder 24 hours after an acute social defeat. The nonselective 5-HT2 receptor agonist mCPP (0.0, 0.3, 1.0 or 3.0 mg/kg) was injected either prior to social defeat training or prior to conditioned defeat testing. Also, the 5-HT2A receptor antagonist MDL 11,939 (0.0, 0.5 or 2.0 mg/kg) was injected either prior to social defeat training or prior to conditioned defeat testing. Injection of mCPP prior to testing increased the expression of conditioned defeat, but injection of mCPP prior to training did not alter the acquisition of conditioned defeat. Conversely, injection of MDL 11,939 prior to training reduced the acquisition of conditioned defeat, but injection of MDL 11,939 prior to testing did not alter the expression of conditioned defeat. Our data suggest that mCPP activates 5-HT2C receptors during testing to enhance the display of submissive and defensive behavior, whereas MDL 11,939 blocks 5-HT2A receptors during social defeat to disrupt the development of the conditioned defeat response. In sum, these results suggest that serotonin acts at separate 5-HT2 receptors to facilitate the acquisition and expression of defeat-induced changes in social behavior.
social defeat; stress; serotonin; anxiety; 5-HT2 receptor
Basolateral amygdala (BLA) function is critical for flexible, goal-directed behavior, including performance on reinforcer devaluation tasks. Here we tested, in rats, the hypothesis that BLA is critical for conditioned reinforcer devaluation during the period when the primary reinforcer (food) is being devalued (by feeding it to satiety), but not thereafter for guiding behavioral choices. We used a spatially-independent task, which employed two visual cues, each predicting one of two foods. An instrumental action (lever press) was required for reinforcer delivery. After training, rats received BLA or sham lesions, or cannulae implanted in BLA. Under control conditions (sham lesions, saline infusions), devaluation of one food significantly decreased responding to the cue associated with that food, when both cues were presented simultaneously during extinction. BLA lesions impaired this devaluation effect. Transient inactivation of BLA by microinfusion of the GABAA agonist muscimol resulted in an impairment, only when BLA was inactivated during satiation. When muscimol was infused after satiation and, therefore, BLA was inactivated only during the choice test, rats showed no impairment. Thus, BLA is necessary for registering or updating cues to reflect updated reinforcer values, but not for guiding choices once the value has been updated. Our results are the first to describe the contribution of rat BLA to specific components of reinforcer devaluation, and are the first to show impairment in reinforcer devaluation following transient inactivation in the rat.
muscimol; pharmacological inhibition; lesion; reward; goal-directed behavior
In recent years, many animal models of memory have focused on one or more of the various components of episodic memory. For example, the odor sequence memory task requires subjects to remember individual items and events (the odors) and the temporal aspects of the experience (the sequence of odor presentation). The well-known spatial context coding function of the hippocampus, as exemplified by place cell firing, may reflect the ‘where’ component of episodic memory. In the present study, we added a contextual component to the odor sequence memory task by training rats to choose the earlier odor in one context and the later odor in another context and we compared the effects of temporary hippocampal lesions on performance of the original single context task and the new dual context task. Temporary lesions significantly impaired the single context task, although performance remained significantly above chance levels. In contrast, performance dropped all the way to chance when temporary lesions were used in the dual context task. These results demonstrate that rats can learn a dual context version of the odor sequence learning task which requires the use of contextual information along with the requirement to remember the ‘what’ and ‘when’ components of the odor sequence. Moreover, the additional requirement of context-dependent expression of the ‘what-when’ memory made the task fully dependent on the hippocampus. Moreover, the addition of the contextual component made the task fully dependent on the hippocampus.
hippocampus; episodic memory; what-where-when; context; sequence memory
Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed an in-depth parametric analysis of human fear extinction using fear-potentiated startle. Using separate single-cue and differential conditioning paradigms, participants were fear conditioned and then underwent extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for spontaneous recovery occurred 96 hr after acquisition. In the single cue paradigm, the Immediate and Delayed groups exhibited differences in context, but not fear, conditioning. With differential conditioning, there were no differences in context conditioning and the Immediate group displayed less spontaneous recovery. Thus, the results remain inconclusive regarding spontaneous recovery and the timing of extinction and are discussed in terms of performing translational studies of fear in humans.
fear conditioning; fear extinction in humans; spontaneous recovery; startle
The current paper examines the effect of administering Dehydroepiandrosterone (DHEA) on visual-spatial performance in post-menopausal women (N=24, ages 55-80). The concurrent reduction of serum DHEA levels and visual-spatial performance in this population, coupled with the documented effects of DHEA’s androgenic metabolites on visual-spatial performance, suggest that DHEA administration may enhance visual-spatial performance. The current experiment used a double-blind placebo-controlled crossover design in which 50 mg of oral DHEA was administered daily in the drug condition to explore this hypothesis. Performance on the Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification, Same-Different Judgment, and Visual Search tasks and serum levels of DHEA, DHEAS, testosterone, estrone and cortisol were measured in the DHEA and placebo conditions. In contrast to prior experiments using the current methodology that did not demonstrate effects of DHEA administration on episodic and short-term memory tasks, the current experiment demonstrated large beneficial effects of DHEA administration on Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification and Same-Different Judgment. Moreover, DHEA administration enhanced serum levels of DHEA, DHEAS, testosterone and estrone, and regression analyses demonstrated that levels of DHEA and its metabolites were positively related to cognitive performance on the visual-spatial tasks in the DHEA condition
Dehydroepiadrosterone (DHEA); post-menopausal women; cognition; visual-spatial tasks; androgens
To examine the effect of discriminative fear conditioning on the shape of the generalization gradient, two groups of participants first learned to discriminate between two color stimuli, one paired with an electrical shock (CS+) and the other explicitly unpaired (CS−). The CS+ was held constant as an intermediate (ambiguous) value along the blue-green color dimension while the CS− varied between groups as opposite endpoints along the blue-green color dimension. Post-discrimination testing, using spectral wavelengths above and below the CS+, revealed opposing asymmetric gradients of conditioned skin conductance responses across training groups that skewed in a direction opposite the CS−. Moreover, perceptual ratings for the color of the CS+ were affected by discriminative conditioning, with the color value of the blue or green CS− inducing a shift in the frequency for ratings of the ambiguous CS+ as either “green” or “blue,” respectively. These results extend findings on gradient shifts in the animal literature, and suggest that post-discrimination testing provides a more comprehensive estimate of the effects of discriminative fear conditioning than testing responses solely to the conditioned stimuli.
anxiety; associative learning; generalization; peak shift; skin conductance responses
Rats suppress intake of a normally preferred 0.15% saccharin conditioned stimulus (CS) when it is paired with an aversive agent like lithium chloride (LiCl) or a preferred substances such as sucrose or a drug of abuse. The reward comparison hypothesis suggests that rats avoid intake of a saccharin cue following pairings with a drug of abuse because the rats are anticipating the availability of the rewarding properties of the drug. The present study used bilateral ibotenic acid lesions to examine the role of the gustatory cortex in the suppression of CS intake induced by cocaine, morphine, and LiCl. The results show that bilateral lesions of the insular gustatory cortex (1) fully prevent the suppressive effects of both a 15- and a 30-mg/kg dose of morphine, (2) attenuate the suppressive effect of a 10 mg/kg dose of cocaine, but (3) are overridden by a 20 mg/kg dose of the drug. Finally, these same cortical lesions had no impact on LiCl-induced conditioned taste aversion. The current data show that the insular taste cortex plays an integral role in drug-induced avoidance of a gustatory CS.
reward comparison; drugs of abuse; anticipatory contrast; avoidance; CTA
Rats avoid intake of a gustatory cue following pairings with a drug of abuse, such as morphine or cocaine. Despite the well-established rewarding properties of these drugs, the reduction in intake of the taste cue has been interpreted as a conditioned taste aversion for decades. In 1997, I proposed the reward comparison hypothesis suggesting that rats avoided intake of the drug-associated taste cue because the value of the taste cue pales in comparison to the highly rewarding drug of abuse expected in the near future. In this issue of Behavioral Neuroscience,
A.C.W. Huang and S. Hsiao (2008) challenge the reward comparison hypothesis by showing parallels between amphetamine and LiCl-induced suppression of CS intake. This commentary addresses the current state of the reward comparison hypothesis in the context of the experiments completed by Huang and Hsiao and their new task-dependent drug effects hypothesis.
anticipatory contrast; sucrose; cocaine; withdrawal; self-administration
Drugs of abuse are known to reduce intake of a taste conditioned stimulus (CS), a behavioral response sometimes seen as paradoxical because the same drugs also serve as rewards in other behavioral procedures. In the present study we compared patterns of intake and palatability (assessed using microstructural analysis of licking) for a standard saccharin CS paired with: lithium chloride, morphine, amphetamine, or sucrose. We found that morphine and amphetamine, like lithium-induced illness, each suppressed CS intake and caused a reduction in saccharin palatability. Sucrose, a rewarding stimulus, did not reduce the palatability of the saccharin CS. We interpret these finds as evidence that drugs of abuse induce conditioned taste aversions.
microstructure; cluster size; morphine; amphetamine; incentive contrast; rats
Like illness-inducing agents (e.g., lithium chloride), drugs of abuse also suppress intake of a taste solution. To explore the nature of this drug-induced intake reduction, in the current study three aqueous stimuli with different initial values served as the conditioned stimuli (CSs) that were paired with a standard dose of amphetamine in a voluntary intake procedure and lick patterns were analyzed. Consistent with earlier studies, amphetamine significantly reduced intake of all three CSs (quinine, sodium chloride and orange odor). In contrast to studies that analyze orofacial responses, we found that lick cluster size was significantly lowered by amphetamine, indicating that the psychoactive drug induced a conditioned change in CS palatability.
licking; microstructure; cluster size; amphetamine; rats