Several lines of evidence indicate that rats emit ultrasonic vocalizations (USVs) in
response to a wide range of stimuli that are capable of producing either euphoric (positive) or
dysphoric (negative) emotional states. On these bases, recordings of USVs are extensively used in
preclinical studies of affect, motivation, and social behavior. Rat USVs are sensitive to the effects
of certain classes of psychoactive drugs, suggesting that emission of rat USVs can have relevance not
only to neurobiology, but also to neuropharmacology and psychopharmacology. This review
summarizes three types of rat USVs, namely 40-kHz USVs emitted by pups, 22-kHz USVs and
50-kHz USVs emitted by young and adult animals, and relevance of these vocalizations to neuropharmacological studies.
Attention will be focused on the issues of how rat USVs can be used to evaluate the pharmacological properties of
different classes of drugs, and how rat USVs can be combined with other behavioral models used in neuropharmacology.
The strengths and limitations of experimental paradigms based on the evaluation of rat USVs will also be discussed.
Analgesic; antidepressant; anxiolytic; drug abuse; drug toxicity; psychostimulant
Pharmacological studies of emotional arousal and initiation of emotional states in rats
measured by their ultrasonic vocalizations are reviewed. It is postulated that emission of
vocalizations is an inseparable feature of emotional states and it evolved from mother-infant
interaction. Positive emotional states are associated with emission of 50 kHz vocalizations that could
be induced by rewarding situations and dopaminergic activation of the nucleus accumbens and are
mediated by D1, D2, and partially D3 dopamine receptors. Three biologically significant subtypes of
50 kHz vocalizations have been identified, all expressing positive emotional states: (1) flat calls
without frequency modulation that serve as contact calls during social interactions; (2) frequencymodulated
calls without trills that signal rewarding and significantly motivated situation; and (3) frequency-modulated
calls with trills or trills themselves that are emitted in highly emotional situations associated with intensive affective state.
Negative emotional states are associated with emission of 22 kHz vocalizations that could be induced by aversive
situations, muscarinic cholinergic activation of limbic areas of medial diencephalon and forebrain, and are mediated by
M2 muscarinic receptors. Two biologically significant subtypes of 22 kHz vocalizations have been identified, both
expressing negative emotional sates: (1) long calls that serve as alarm calls and signal external danger; and (2) short calls
that express a state of discomfort without external danger. The positive and negative states with emission of vocalizations
are initiated by two ascending reticular activating subsystems: the mesolimbic dopaminergic subsystem as a specific
positive arousal system, and the mesolimbic cholinergic subsystem as a specific negative arousal system.
Appetitive state; aversive state; cholinergic system; dopaminergic system; emotional arousal; 22 kHz calls; 50 kHz calls; ultrasonic calls
The present review describes ways in which ultrasonic vocalizations (USVs) have been used in studies of substance abuse. Accordingly, studies are reviewed which demonstrate roles for affective processing in response to the presentation of drug-related cues, experimenter- and self-administered drug, drug withdrawal, and during tests of relapse/reinstatement. The review focuses on data collected from studies using cocaine and amphetamine, where a large body of evidence has been collected. Data suggest that USVs capture animals’ initial positive reactions to psychostimulant administration and are capable of identifying individual differences in affective responding. Moreover, USVs have been used to demonstrate that positive affect becomes sensitized to psychostimulants over acute exposure before eventually exhibiting signs of tolerance. In the drug-dependent animal, a mixture of USVs suggesting positive and negative affect is observed, illustrating mixed responses to psychostimulants. This mixture is predominantly characterized by an initial bout of positive affect followed by an opponent negative emotional state, mirroring affective responses observed in human addicts. During drug withdrawal, USVs demonstrate the presence of negative affective withdrawal symptoms. Finally, it has been shown that drug-paired cues produce a learned, positive anticipatory response during training, and that presentation of drug-paired cues following abstinence produces both positive affect and reinstatement behavior. Thus, USVs are a useful tool for obtaining an objective measurement of affective states in animal models of substance abuse and can increase the information extracted from drug administration studies. USVs enable detection of subtle differences in a behavioral response that might otherwise be missed using traditional measures.
Addiction; affect; emotion; stimulant; ultrasonic vocalizations
Vocal communication is negatively affected by neurodegenerative diseases, such as
Parkinson disease, and by aging. The neurological and sensorimotor mechanisms underlying voice
deficits in Parkinson disease and aging are not well-understood. Rat ultrasonic vocalizations provide a
unique behavioral model for studying communication deficits and the mechanisms underlying these deficits in these
conditions. The purpose of this review was to examine the existing literature for methods using rat ultrasonic vocalization
with regard to the primary disease pathology of Parkinson disease, dopamine denervation, and aging. Although only a
small amount of papers were found for each of these topics, results suggest that both shared and unique acoustic deficits in
ultrasonic vocalizations exist across conditions and that these acoustic deficits are due to changes in either dopamine
signaling or denervation and in aging models changes to the nucleus ambiguus, at the level of the neuromuscular junction,
and the composition of the vocal folds in the larynx. We conclude that ultrasonic vocalizations are a useful tool for
studying biologic mechanisms underlying vocal communication deficits in neurodegenerative diseases and aging.
Aging; dopamine; rat; ultrasonic vocalization; voice; 6-OHDA.
Rats emit high-frequency 50-kHz ultrasonic vocalizations (USV) in appetitive situations like social interactions. Drugs of abuse are probably the most potent non-social elicitors of 50-kHz USV, possibly reflecting their euphorigenic properties. Psychostimulants induce the strongest elevation in 50-kHz USV emission, particularly amphetamine (AMPH), either when applied systemically or locally into the nucleus accumbens (Nacc). Emission of AMPH-induced 50-kHz USV depends on test context, such as the presence of conspecifics, and can be manipulated pharmacologically by targeting major neurotransmitter systems, including dopamine (DA), noradrenaline (NA), and serotonin (5-HT), but also protein kinase C (PKC) signaling. Several D1 and D2 receptor antagonists, as well as typical and atypical antipsychotics block the AMPH-induced elevation in 50-kHz USV. Inhibiting D1 and D2 receptors in the Nacc abolishes AMPH-induced 50-kHz USV, indicating a key role for this brain area. NA neurotransmission also regulates AMPH-induced 50-kHz USV emission given that α1 receptor antagonists and α2 receptor agonists exert attenuating effects. Supporting the involvement of the 5-HT system, AMPH-induced 50-kHz USV are attenuated by 5-HT2C receptor activation, whereas 5-HT2C receptor antagonism leads to the opposite effect. Finally, treatment with lithium, tamoxifen, and myricitrin was all found to result in a complete abolishment of the AMPH-induced increase in 50-kHz USV, suggesting the involvement of PKC signaling. Neurotransmitter systems involved in AMPH-induced 50-kHz USV emission only partially overlap with other AMPH-induced behaviors like hyperlocomotion. The validity of AMPH-induced 50-kHz USV as a preclinical model for neuropsychiatric disorders is discussed, particularly with relevance to altered drive and mood seen in bipolar disorder.
Amphetamine; antipsychotics; dopamine; lithium; serotonin; ultrasonic vocalizations.
Voltage-gated ion channels are key regulators of cell excitability. There is significant evidence that these channels are subject to modulation by redox status of the cells. Here we review the post-translational modifications of ion channels that occur in colonic inflammation. The redox mechanisms involve tyrosine nitration, covalent modification of cysteine residues and sulfhydration by hydrogen sulfide in experimental colitis. In the setting of colonic inflammation, modifications of cysteine and tyrosine are likely to occur at several sites within the same channel complex. In this review we describe alterations in channel function due to specific modifications of tyrosine and cysteine residues by reactive nitrogen, oxygen and hydrogen-sulfide resulting in altered motility.
Calcium channel; hydrogen sulfide; oxidative stress; tyrosine nitration.
Epilepsy has 2-3% incidence worldwide. However, present antiepileptic drugs provide only partial control of seizures. Calcium ion accumulation in hippocampal neurons has long been known as a major contributor to the etiology of epilepsy. TRPV1 is a calcium-permeable channel and mediator of epilepsy in the hippocampus. TRPV1 is expressed in epileptic brain areas such as CA1 area and dentate gyrus of the hippocampus. Here the author reviews the patent literature on novel molecules targeting TRPV1 that are currently being investigated in the laboratory and are candidates for future clinical evaluation in the management of epilepsy.
A limited number of recent reports have implicated TRPV1 in the induction or treatment of epilepsy suggesting that this may be new area for potential drugs targeting this debilitating disease. Thus activation of TRPV1 by oxidative stress, resiniferatoxin, cannabinoid receptor (CB1) activators (i.e. anandamide) or capsaicin induced epileptic effects, and these effects could be reduced by appropriate inhibitors, including capsazepine (CPZ), 5'-iodoresiniferatoxin (IRTX), resolvins, and CB1 antagonists. It has been also reported that CPZ and IRTX reduced spontaneous excitatory synaptic transmission through modulation of glutaminergic systems and desensitization of TRPV1 channels in the hippocampus of rats. Immunocytochemical studies indicated that TRPV1 channel expression increased in the hippocampus of mice and patients with temporal lobe epilepsy
Taken together, findings in the current literature support a role for calcium ion accumulation through TRPV1 channels in the etiology of epileptic seizures, indicating that inhibition of TRPV1 in the hippocampus may possibly be a novel target for prevention of epileptic seizures.
Anadamide; Calcium ion; Epilepsy; Hippocampus; Seizures; TRPV1 channels
Psychiatric and neurological disorders are mostly associated with the changes in neural
calcium ion signaling pathways required for activity-triggered cellular events. One calcium channel
family is the TRP cation channel family, which contains seven subfamilies. Results of recent papers
have discovered that calcium ion influx through TRP channels is important. We discuss the latest
advances in calcium ion influx through TRP channels in the etiology of psychiatric disorders.
Activation of TRPC4, TRPC5, and TRPV1 cation channels in the etiology of psychiatric disorders
such as anxiety, fear-associated responses, and depression modulate calcium ion influx. Evidence substantiates that
anandamide and its analog (methanandamide) induce an anxiolytic-like effect via CB1 receptors and TRPV1 channels.
Intracellular calcium influx induced by oxidative stress has an significant role in the etiology of bipolar disorders (BDs),
and studies recently reported the important role of TRP channels such as TRPC3, TRPM2, and TRPV1 in converting
oxidant or nitrogen radical signaling to cytosolic calcium ion homeostasis in BDs. The TRPV1 channel also plays a
function in morphine tolerance and hyperalgesia. Among psychotropic drugs, amitriptyline and capsazepine seem to have
protective effects on psychiatric disorders via the TRP channels. Some drugs such as cocaine and methamphetamine also
seem to have an important role in alcohol addiction and substance abuse via activation of the TRPV1 channel.
Thus, we explore the relationships between the etiology of psychiatric disorders and TRP channel-regulated mechanisms.
Investigation of the TRP channels in psychiatric disorders holds the promise of the development of new drug treatments.
Anandamide; anxiety; bipolar disorders; calcium ion; depression; TRP channels
The transient receptor potential (TRP) proteins are a family of ion channels that act as
cellular sensors. Several members of the TRP family are sensitive to oxidative stress mediators.
Among them, TRPA1 is remarkably susceptible to various oxidants, and is known to mediate
neuropathic pain and respiratory, vascular and gastrointestinal functions, making TRPA1 an
attractive therapeutic target. Recent studies have revealed a number of modulators (both activators and inhibitors) that act
on TRPA1. Endogenous mediators of oxidative stress and exogenous electrophiles activate TRPA1 through oxidative
modification of cysteine residues. Non-electrophilic compounds also activate TRPA1. Certain non-electrophilic
modulators may act on critical non-cysteine sites in TRPA1. However, a method to achieve selective modulation of
TRPA1 by small molecules has not yet been established. More recently, we found that a novel N-nitrosamine compound
activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol), and does so with
significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred
through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic
moiety on the N-nitrosamine. In this review, we describe the molecular pharmacology of these TRPA1 modulators and
discuss their modulatory mechanisms.
Electrophile; non-electrophilic compound; oxidative stress; transnitrosylation; TRP channel; TRPA1
There is rapidly growing evidence indicating multiple and important roles of Ca2+-permeable cation TRP channels in the airways, both under normal and disease conditions. The aim of
this review was to summarize the current knowledge of TRP channels in sensing oxidative, chemical irritant and temperature stimuli by discussing expression and function of several TRP channels in
relevant cell types within the respiratory tract, ranging from sensory neurons to airway smooth muscle and epithelial cells. Several of these channels, such as TRPM2, TRPM8, TRPA1 and
TRPV1, are discussed in much detail to show that they perform diverse, and often overlapping or contributory, roles in airway hyperreactivity, inflammation, asthma, chronic obstructive pulmonary disease and other
respiratory disorders. These include TRPM2 involvement in the disruption of the bronchial epithelial tight junctions during oxidative stress, important roles of TRPA1 and TRPV1 channels in airway inflammation, hyperresponsiveness,
chronic cough, and hyperplasia of airway smooth muscles, as well as TRPM8 role in COPD and mucus hypersecretion. Thus, there is increasing evidence that TRP channels not only function as an integral part of the important endogenous
protective mechanisms of the respiratory tract capable of detecting and ensuring proper physiological responses to various oxidative, chemical irritant and temperature stimuli, but that altered expression, activation and regulation of these
channels may also contribute to the pathogenesis of respiratory diseases.
Airway disease; air pollution; calcium signaling; oxidative stress; TRP channel
The use of anabolic-androgenic steroids (AASs) by professional and recreational athletes is
increasing worldwide. The underlying motivations are mainly performance enhancement and body image improvement.
AAS abuse and dependence, which are specifically classified and coded by the DSM-5, are not uncommon. AAS-using
athletes are frequently present with psychiatric symptoms and disorders, mainly somatoform and eating, but also mood,
and schizophrenia-related disorders. Some psychiatric disorders are typical of athletes, like muscle dysmorphia. This
raises the issue of whether AAS use causes these disorders in athletes, by determining neuroadaptive changes in the reward
neural circuit or by exacerbating stress vulnerability, or rather these are athletes with premorbid abnormal personalities or
a history of psychiatric disorders who are attracted to AAS use, prompted by the desire to improve their appearance and
control their weights. This may predispose to eating disorders, but AASs also show mood destabilizing effects, with longterm
use inducing depression and short-term hypomania; withdrawal/discontinuation may be accompanied by depression.
The effects of AASs on anxiety behavior are unclear and studies are inconsistent. AASs are also linked to psychotic
behavior. The psychological characteristics that could prompt athletes to use AASs have not been elucidated.
Anabolic-androgenic steroids; doping; mood disorders; psychopathology; psychosis
New psychoactive substances (NPS) have completely modified the drug scene and the
current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also
known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine,
methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic
cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for
NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use.
All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant
feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or
toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the
potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly
informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic
cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on
PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination:
“new psychoactive substances”, “synthetic cathinones”, “substituted cathinones”, “mephedrone”, “methylone”, “MDPV”,
“4-MEC”, “addiction”, and “substance use disorder”.
Addiction; MDPV; 4-MEC; mephedrone; methylone; new psychoactive substances; substance use disorder; substituted cathinones; synthetic cathinones
Nandrolone is included in the class II of anabolic androgenic steroids (AAS) which is
composed of 19-nor-testosterone-derivates. In general, AAS is a broad and rapidly increasing group
of synthetic androgens used both clinically and illicitly. AAS in general and nandrolone decanoate
(ND) in particular have been associated with several behavioral disorders. The purpose of this review
is to summarize the literature concerning studies dealing with ND exposure on animal models, mostly
rats that mimic human abuse systems (i.e. supraphysiological doses). We have focused in particular
on researches that have investigated how ND alters the function and expression of neuronal signaling molecules that
underlie behavior, anxiety, aggression, learning and memory, reproductive behaviors, locomotion and reward.
Nandrolone decanoate (ND); Anabolic androgenic steroids (AAS); neurological effects; anxiety; aggression; learning and memory
Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone
that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a
great number of organs and systems are a target of AAS, their adverse effects are primarily on the
following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological,
infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral
effects as a result of AAS abuse are well known and described in the literature. Mounting evidence
exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS
carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal
studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal
susceptibility to apoptotic stimuli.
Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced
neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular
oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive
impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS – induced neuropathology
could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will
provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way
for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the
possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented
Androgen-anabolic steroids; apoptosis; biochemical mechanisms; excitotoxic neuronal death; neurotrophin unbalance; neuroprotective strategies; neurotoxicity; oxidative-stress
Anabolic androgenic steroids (AASs) represent a large group of synthetic derivatives of testosterone, produced to maximize anabolic effects and minimize the androgenic ones. AAS can be administered orally, parenterally by intramuscular injection and transdermally. Androgens act by binding to the nuclear androgen receptor (AR) in the cytoplasm and then translocate into the nucleus. This binding results in sequential conformational changes of the receptor affecting the interaction between receptor and protein, and receptor and DNA.
Skeletal muscle can be considered as the main target tissue for the anabolic effects of AAS, which are mediated by ARs which after exposure to AASs are up-regulated and their number increases with body building. Therefore, AASs determine an increase in muscle size as a consequence of a dose-dependent hypertrophy resulting in an increase of the cross-sectional areas of both type I and type II muscle fibers and myonuclear domains. Moreover, it has been reported that AASs can increase tolerance to exercise by making the muscles more capable to overload therefore shielding them from muscle fiber damage and improving the level of protein synthesis during recovery.
Despite some therapeutic use of AASs, there is also wide abuse among athletes especially bodybuilders in order to improve their performances and to increase muscle growth and lean body mass, taking into account the significant anabolic effects of these drugs.
The prolonged misuse and abuse of AASs can determine several adverse effects, some of which may be even fatal especially on the cardiovascular system because they may increase the risk of sudden cardiac death (SCD), myocardial infarction, altered serum lipoproteins, and cardiac hypertrophy.
The aim of this review is to focus on deaths related to AAS abuse, trying to evaluate the autoptic, histopathological and toxicological findings in order to investigate the pathophysiological mechanism that underlines this type of death, which is still obscure in several aspects. The review of the literature allowed us to identify 19 fatal cases between 1990 and 2012, in which the autopsy excluded in all cases, extracardiac causes of death.
Anabolic Androgenic Steroids (AAS); cardiovascular effects; sudden cardiac death; toxicity
Synthetic cathinones are designer drugs of the phenethylamine class, structurally and pharmacologically similar to amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), cathinone and other related substances. New analogues, legal at least, until formally banned (a time consuming process), are introduced almost daily The United Nations estimates nearly 250 new drug analogues are produced per year. Various combinations of these drugs are sold under the name of “bath salts”. They can be ingested by any route and some appear capable of causing great harm, mostly behavioral. One drug in particular, MDVP, appears to frequently cause symptoms indistinguishable from the classic findings in Excited Delirium Syndrome (ExDS). Little is known about the pathology or clinical toxicology of these drugs but their molecular mechanism of action seems to be identical with that of cocaine. This mini-review examines what little is known on the subject and explains the suspected
mechanisms of excited delirium syndrome.
“Bath salts”; cathinones; methedrone; methelone; MDMA; MDVP
The definition New psychoactive substances (NPS) refers to emerging drugs whose
chemical structures are similar to other psychoactive compounds but not identical, representing a
“legal” alternative to internationally controlled drugs. There are many categories of NPS, such as
synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives
and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino
acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring
and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as
other compounds known for their hallucinogenic properties, such as psilocybin in ‘Magic mushrooms’ and
dimethyltryptamine (DMT) in Ayahuasca brews.
To review the scientific literature regarding tryptamines and their derivatives, providing a summary of all the
available information about the structure of these compounds, their effects in relationship with the routes of
administration, their pharmacology and toxicity, including articles reporting cases of death related to intake of these
A comprehensive review of the published scientific literature was performed, using also non peer-reviewed
information sources, such as books, government publications and drug user web fora.
Information from Internet and from published scientific literature, organized in the way we proposed in this
review, provides an effective tool for specialists facing the emerging NPS threat to public health and public security,
including the personnel working in Emergency Department.
Clinical effects; Emergency Departments; Fatalities; Forensic Toxicology; Intoxication; New Psychoactive Substances (NPS); Tryptamines.
The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous
system depressant and is often encountered during forensic investigations of living and deceased
persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some
countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant
medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced
endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a
precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information
indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to
the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues,
owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated.
After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and
GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in
urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug
use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a
concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from
cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The
poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis.
After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to
unpleasant withdrawal symptoms. There is no evidence-based protocol available to deal with GHB withdrawal, apart from
Analogues; γ-hydroxybutyrate (GBH); intoxication; overdose; pharmacodynamics; pharmacokinetics; treatment; withdrawal syndrome
Cognitive enhancement can be defined as the use of drugs and/or other means with the
aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity
and intelligence in the absence of any medical indication. Currently, it represents one of the most
debated topics in the neuroscience community. Human beings always wanted to use substances to
improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt
to allow them to better communicate with their gods, to the widespread use of caffeine under various
forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators.
In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only
a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on
healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as
Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk
in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive
enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the
ethical considerations surrounding human enhancement has been examined.
Anabolic androgenic steroids (AAS); cosmetic neurology; Human enhancement; methylphenidate; smart drugs
Caffeine use is increasing worldwide. The underlying motivations are mainly concentration
and memory enhancement and physical performance improvement. Coffee and caffeine-containing
products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and
the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects.
Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore,
caffeine abuse and dependence are becoming more and more common and can lead to caffeine
intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main
findings concerning caffeine’s mechanisms of action (focusing on adenosine antagonism, intracellular calcium
mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests
that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal
role in intoxication or death. This could be due to caffeine’s interaction with other substances or to the individuals' preexisting
metabolism alterations or diseases.
Abuse; caffeine; coffee; dependence; energy drinks; safety doses; toxicity
Anabolic androgenic steroids (AAS) are some of the most common performance
enhancing drugs (PED) among society. Despite the broad spectrum of adverse effects and legal
consequences, AAS are illicitly marketed and distributed in many countries. To circumvent existing
laws, the chemical structure of AAS is modified and these designer steroids are sold as nutritional
supplements mainly over the Internet. Several side effects are linked with AAS abuse. Only little is
known about the pharmacological effects and metabolism of unapproved steroids due to the absence
of clinical studies. The large number of designer steroid findings in dietary supplements and the
detection of new compounds combined with legal loopholes for their distribution in many countries
show that stricter regulations and better information policy are needed.
AAS; designer steroids; dietary supplements; performance enhancing drugs.
Diabetes mellitus (DM) is a metabolic disease that is rapidly increasing and has become a major public health problem. Type 2 DM (T2DM) is the most common type, accounting for up to 90-95% of the new diagnosed DM cases. The brain is very susceptible to glucose fluctuations and hyperglycemia-induced oxidative stress (OS). It is well known that DM and the risk of developing neurodegenerative diseases are associated. Tea, Camellia sinensis L., is one of the most consumed beverages. It contains several phytochemicals, such as polyphenols, methylxanthines (mainly caffeine) and L-theanine that are often reported to be responsible for tea’s health benefits, including in brain. Tea phytochemicals have been reported to be responsible for tea’s significant antidiabetic and neuroprotective properties and antioxidant potential. Epidemiological studies have shown that regular consumption of tea has positive effects on DM-caused complications and protects the brain against oxidative damage, contributing to an improvement of the cognitive function. Among the several reported benefits of tea consumption, those related with neurodegenerative diseases are of great interest. Herein, we discuss the potential beneficial effects of tea consumption and tea phytochemicals on DM and how their action can counteract the severe brain damage induced by this disease.
Brain; caffeine; catechins; diabetes mellitus; L-theanine; tea