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. Theworking hypothesis of this grant is that CRF and NE are also involved in escalation of heroinself-administration in rats that have long-access to heroin. Initially, rats will be allowed to nose-poke forfood and water in a self-administration box. Rats will have i.v. catheters and bilateral intra-BNST cannulaeimplanted. After recovery from surgery and subsequent food- and water-training, rats will be given 23-hraccess to heroin on a fixed ratio of 1 with a 20 sec timeout. To examine the effect of CRF and NE in theBNST on opiate dependence, CRF and NE antagonists will be injected 15 mins prior to the active phase (6PM; lights off) of the light/dark cycle. In addition, a separate study, using tract-tracing combined with in situhybridization, will examine the projections of CRF- and adrenergic-receptor cells from the BNST toreward-relevant areas. These studies will further our understanding of a role for the BNST in themotivational 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 |
