THE DYNAMIC INTERACTION BETWEEN CIRCADIAN RHYTHMS AND DRUG-TAKING: EVIDENCE FROM BEHAVIOR ANALYSES IN RATS
Browning, Jenny Raye
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Extensive research links circadian rhythms and drug addiction. In this thesis I examined the interaction between circadian rhythms and drug-taking. In my first experiment, I studied the effect of free-running (non-entrained) circadian rhythms on cocaine self-administration reinstatement, a model of drug relapse. Contrary to my original hypothesis that disruption to the circadian system would lead to increased likelihood of relapse, I found that the animals maintained in a light cycle that prevented entrainment actually showed lower reinstatement compared to animals maintained in a normal light/dark cycle. In my second experiment, I examined the effects of circadian and daily rhythms on cocaine-taking more directly by giving animals self-administration training at two different times of the day (light or dark phase) in a normal light cycle, or at two times of the subjective day (subjective day or subjective night) in constant, free-running conditions. In addition, I studied the effects of cocaine self-administration at these different time points on circadian and daily rhythms. As expected, rats self-administered more cocaine during the dark phase and the subjective night compared to the light phase and the subjective day respectively. This was expected because the rats used were nocturnal and thus motivation for cocaine was expected to be higher during the night (active phase). Furthermore, cocaine self-administration was able to shift circadian rhythms at both time points in animals held in constant conditions, an effect not seen control animals trained to self-administer saline. In animals trained while maintained in a standard light/dark cycle, animals trained at the end of the dark phase entrained to the start of the self-administration session, whereas animals trained during the light phase showed no effect of self-administration. In my last experiment, I show evidence that the anterior paraventricular thalamus (aPVT) is ideally situated to integrate information from the circadian and addiction centers in the brain. Furthermore, I show that inactivation of the aPVT abolishes the expression of cocaine conditioned place preference in rats.