Neuronal Mechanisms Mediating Acute Food Deprivation-Induced Reinstatement of Heroin Seeking

Neuronal Mechanisms Mediating Acute Food Deprivation-Induced Reinstatement of Heroin Seeking Stephanie Tobin, Ph.D. Concordia University, 2012 One of the most troubling aspects of addiction is the chronic and cyclical nature of this disorder. In particular, the desire to use drugs and subsequent relapse can occur after months or even years of absence. Amongst human drug abusers, exposure to stressful life events and style of stress-coping have been shown to predict relapse. Similarly, in rodents stress can induce the reinstatement of drug seeking, a model of stress-induced relapse. In the following series of experiments the neuronal mechanisms mediating acute 21-48h food deprivation (FD)-induced reinstatement of heroin seeking are investigated. Previously, our laboratory has demonstrated that this form of reinstatement can be attenuated by systemic injection of the dopamine (DA) D1 receptor antagonist SCH 23390. Thus, in chapter 1, the neuronal circuitry mediating the role of DA, acting at the D1 receptor, in acute FD-induced reinstatement was examined. The five experiments described in the chapter reveal a significant attenuation of heroin seeking in rats infused with SCH 23390 into the nucleus accumbens (NAc) shell, dorsal medial prefrontal cortex (dmPFC) or basolateral amygdala (BLA). However, acute FD-induced reinstatement was not affected by infusions of SCH 23390 into the NAc core, or ventral medial prefrontal cortex (vmPFC). Compulsive drug seeking and the propensity to relapse have been attributed to pathological synaptic plasticity, resulting from drug-induced changes in glutamate synapses. Thus, in chapters 2 and 3 the role of glutamate in acute FD-induced