? Little is known about the role of the bed nucleus of the stria terminalis (BNST) in opiate dependence. Recent studies have described an involvement of corticotropin-releasing factor (CRF) and norepineprine (NE) in the BNST in opiate withdrawal and stress-induced reinstatement of opiate administration. The working hypothesis of this grant is that CRF and NE are also involved in escalation of heroin self-administration in rats that have long-access to heroin. Initially, rats will be allowed to nose-poke for food and water in a self-administration box. Rats will have i.v. catheters and bilateral intra-BNST cannulae implanted. After recovery from surgery and subsequent food- and water-training, rats will be given 23-hr access to heroin on a fixed ratio of 1 with a 20 sec timeout. To examine the effect of CRF and NE in the BNST on opiate dependence, CRF and NE antagonists will be injected 15 mins prior to the active phase (6 PM; lights off) of the light/dark cycle. In addition, a separate study, using tract-tracing combined with in situ hybridization, will examine the projections of CRF- and adrenergic-receptor cells from the BNST to reward-relevant areas. These studies will further our understanding of a role for the BNST in the motivational effects of opiate dependence. ? ? ? ? ?
| Greenwell, Thomas N; Funk, Cindy K; Cottone, Pietro et al. (2009) Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long- but not short-access rats. Addict Biol 14:130-43 |
| Greenwell, Thomas N; Walker, Brendan M; Cottone, Pietro et al. (2009) The alpha1 adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration. Pharmacol Biochem Behav 91:295-302 |
