The primary focus of the proposed work is to examine the role of neuropeptides, namely galanin and corticotrophin releasing factor (CRF), in opiate dependence. The predominance of galanin receptors in the locus coeruleus (LC) and their interaction with mu-opiate receptors have raised the possibility for galanin to play a role in opiate dependence. In addition, pharmacological studies involving non-specific and specific CRF receptor blockade have demonstrated a role for CRF systems in opiate dependence. Initially, rats will be allow to nose-poke for food and water in a self-administration box. The animals will then undergo surgery for i.v. catheterization and/or intracerebroventricular cannulation. After recovery from surgery, rats will receive a reinstatement of food- and water-training days. After this period, rats will be given access to drug level on a FR1-20 sec schedule for 23 hours daily. To examine the effect of galanin and CRF on the expression of opiate dependence, the respective agonists and/or antagonists will be injected 15 minutes prior to the active phase (6pm; lights off) of the light-dark cycle. These studies will further our understanding of neuropeptide-opiate interactions that possibly underlie the motivational aspects of opiate dependency.
Chen, Scott A; O'Dell, Laura E; Hoefer, Michael E et al. (2006) Unlimited access to heroin self-administration: independent motivational markers of opiate dependence. Neuropsychopharmacology 31:2692-707 |