Abstract

North America is in the midst of an opioid crisis. Many individuals who suffer from addiction to opioids attempt to stop using the drug. However, many of these individuals often find it difficult to maintain abstinence and ultimately end up relapsing, starting the vicious cycle of addiction all over again. In both human and animal models of drug addiction, chronic food restriction increases rates of relapse. Our laboratory has previously demonstrated a robust increase in drug-seeking following a period of abstinence in chronically food-restricted rats compared to their sated counterparts. To date, the neural mechanisms that mediate the effect of chronic food restriction on drug-seeking remain elusive. However, the paraventricular nucleus of the thalamus (PVT) appears to be a promising candidate to investigate. The PVT is uniquely situated to contribute to homeostatic and drug-seeking systems. Thus, this thesis aimed to examine the role of the PVT in the augmentation of heroin seeking induced by chronic food restriction using a chemogenetic approach. In the first series of experiments, we sought to determine if the PVT plays a role in heroin seeking in chronically food-restricted rats following a period of abstinence. Here, we showed that chemogenetically activating the PVT abolishes heroin seeking in chronically food-restricted rats indicating that the PVT does play a role in this phenomenon. Next, we investigated the role of the input from the prelimbic cortex to the PVT. Here, we did not observe any changes in heroin seeking behaviour in chronically food-restricted or sated rats when we activated or inhibited this pathway despite verifying that chemogenetic manipulations were sufficient to alter neuronal activity. In the last series of experiments, we assessed the role of the output from the PVT to the nucleus accumbens (NAc). We demonstrated that chemogenetically activating PVT projections to the NAc shell, but not core, abolished the augmentation of heroin seeking in chronically food-restricted rats. Taken together, the findings presented in this thesis indicate that the PVT and its projection to the NAc shell play a critical role in the regulation of heroin seeking in chronically food-restricted rats following a period of abstinence.