The results of this study demonstrate that, after repeated cocaine exposure in the presence of music, rats developed a conditioned context preference (CCP) for the music. This was illustrated by animals spending significantly more time in the presence of the music associated with cocaine than their respective controls. These results are consistent with other recent studies showing that music can be used effectively as a contextual CS in rats (Feduccia & Duvauchelle, 2008
; Otsuka et al., 2009
; Polston et al., 2011
). Furthermore, our findings are consistent with other CPP experiments showing that repeated administration of a drug in a particular environment causes animals to subsequently develop a preference for that environment (Bardo et al., 1995
; McCallum & Glick, 2009
; Tzschentke, 2007
). Although our results are comparable to the results usually achieved with CPP, one major difference in our approach was that we used a different apparatus and setting for conditioning sessions than we used for test sessions. Therefore, our animals were not conditioned to environmental cues within a particular place. Instead, they were conditioned to a contextual cue in a different environment, which in this case happened to be music. Conditioning and testing in different environments provided more certainty that music was the determining factor accounting for the CCP effect.
Another interesting finding was that our animals who received cocaine conditioning with music showed significantly higher locomotor activity during final testing than controls. Previous studies pairing rewarding drugs with simple CS have shown similar locomotor effects (Bevins, Besheer, & Pickett, 2001
; Rodríguez-Borrero et al., 2006
). Our findings are also corroborated by recent studies showing the impact of a musical CS on locomotor activity (Feduccia & Duvauchelle, 2008
; Polston et al., 2011
). One potential confound in our study might be that we did not adequately control for the residual effects of cocaine itself. While it is possible that four consecutive days of cocaine administration could account for our observed CCP and locomotor effects, it is highly unlikely. In previous experiments, using a similar classical conditioning procedure, we included explicitly non-paired and no-music controls and did not see a significant locomotor effect (Polston et al., 2011
Another factor to be considered is the possibility that habituation may play a role in the locomotor effect during final testing. It is evident from and that, in both experiments, the animals that were not conditioned with cocaine showed significantly decreased locomotor activity when compared to either group during baseline testing. However, the apparatus was novel during baseline testing, and one would expect to see more exploratory behavior during this session as compared to the final testing session, when all animals would have had experience with the apparatus. Therefore, the data of the test and control animals during final testing are the most important data to compare; and this analysis clearly shows that the cocaine/music animals exhibited greater locomotion when compared to that of their respective controls. The most parsimonious explanation for this effect would appear to be that, after pairing the music with cocaine, the music itself evoked memories of cocaine reward, resulting in psychomotor activation.
It could also be argued that the CCP effect we found should be described as “decreased avoidance” or “decreased aversion” rather than as increased preference. That is, in Experiment 1 our animals did not shift to spending greater than half the test session in the compartment featuring drug-paired music, and thus did not exhibit what is termed as “absolute preference” (Tzschentke, 1998
). However, decreased avoidance or aversion does not accurately reflect the operational definition of what constitutes a CPP effect, and therefore should not reflect what we term a CCP effect. The criterion for establishing a CPP effect is not that animals spend greater than half of the test session in one compartment, it is that they show significantly increased preference when compared to their respective controls during final testing. Indeed, in an unbiased
CPP design, where the animals spend roughly equal amounts of time on both sides of the apparatus during baseline testing, it is quite common for animals to have spent greater than half the session on the drug-paired side during final testing. However, when using a biased
CPP apparatus, particularly one that produces significant bias
during baseline testing, one can show a CPP effect without the animals spending greater than half the session on the drug-paired side during final testing. Therefore, especially in Experiment 1, where animals showed a significant bias for one condition over the other, it is unnecessary for subjects to have spent more than half the test session in the presence of the drug-paired music to be able to refer to the effect as increased preference or CCP; it is only necessary for subjects to have spent significantly more time in the presence of the drug-paired music than their respective controls.
While the main purpose of this study was to determine whether music was an effective contextual CS, we were also interested in determining what an animal’s preference might be for particular kinds of music, and whether rats would prefer music or silence. The results clearly indicate that rats prefer Beethoven’s “Fur Elise” over Miles Davis’ “Four”, and that they prefer silence to Beethoven. We used the music that they had most preferred when we tested music vs. silence, and they still significantly preferred silence during baseline testing. However, in both conditions (music vs. music, music vs. silence), we were able to induce a CCP by pairing the music with cocaine. Our results suggest that rats do not find music rewarding, consistent with previous investigations (Feduccia & Duvauchelle, 2008
; Otsuka et al., 2009
). The fact that music is not apparently rewarding to rats may potentially make it more attractive as a contextual CS in animal models; that is, if rats experienced pleasure from the music alone, this would further complicate analysis and interpretation.
Evolutionary considerations may help explain why a particular species finds music rewarding. In the current experiments, the music was clearly composed and arranged by human beings. Therefore, it is highly likely that what the rat is hearing in our experiments is quite different from that heard and interpreted by a typical human. To address the reinforcing quality of music in other species, it may be necessary for the music to match that particular animal species’ audiogram (Otsuka et al., 2009
). More advanced techniques may be necessary to adequately address whether an animal finds music rewarding. In our experiments, the rats were not able to control volume, and had little control over musical selection. However, the main purpose of this study was not to determine whether rats like music, or had an appreciation for Beethoven and Miles Davis, it was to determine whether they could differentiate between two contrasting pieces of music. In order for music to be an effective contextual CS in rats, they need to be able to recognize and distinguish between complex sound arrangements, and it certainly appears that rats have this capability.
Pleasurable music induces neurological responses in humans that are comparable to the effects induced by drugs of abuse. For instance, highly enjoyable music has been shown to activate reward-related brain regions such as the nucleus accumbens, ventral tegmental area, amygdala, and prefrontal cortex. Enhanced functional connectivity between brain regions that mediate reward may help explain why listening to music is regarded as a highly pleasurable human experience (Blood & Zatorre, 2001
; Menon & Levitin, 2005
). It has also been demonstrated that music increases dopaminergic neurotransmission (Sutoo & Akiyama, 2004
). The fact that human beings find music rewarding may help explain why music therapy has shown such promising results across a vast spectrum of disorders.
Although there are many conceivable and potential therapeutic uses for music, it may not be practical or possible to assess some of these directly in humans. For instance, it has been shown that contextual CS have the ability to reinstate drug seeking behavior in rats (Crombag, Bossert, Koya, & Shaham, 2008
; Fuchs et al., 2008
). What has not been shown is whether a contextual CS has the ability to attenuate drug seeking and relapse behaviors. If one were to pair a drug known to attenuate drug-seeking with a particular musical selection, it is possible that the musical CS alone could then attenuate drug-seeking behavior. For ethical reasons, it would likely not be feasible to propose doing this kind of study initially in human beings. Therefore, it is prudent for investigators to have preclinical animal models involving music that could be utilized in situations where testing on humans proves impractical. Studies illustrating that music can serve as an effective contextual CS in rats are an important first step in creating preclinical models that involve music.
While the influence of simple CS on goal directed behavior has been studied comprehensively, more complex contextual CS have not been adequately explored. Utilization of a complex contextual music cue allowed for examination of associative learning that may be comparable to the psychological processes that occur during subjective human drug experiences. Although there is ample literature demonstrating that cue-elicited craving is a fundamental component of addiction, there are still many factors that are not entirely understood (Volkow et al., 2006
). The present study is the first to give instrumental control of musical choice to a lower order species. This was done to examine whether a rodent could differentiate between musical selections, and more importantly, to determine if music could function as an effective contextual CS in rats. Our results suggest that rats do show preferences for particular kinds of music, and that these preferences can be altered after drug-paired conditioning. Furthermore, this work demonstrates that music does serve as an effective contextual CS in rats, and that this species is a viable option for use in other preclinical models utilizing musical intervention.