The purpose of this research is to further delineate the neural substrates of ethanol (EtOH) dependence through the investigation of the motivational effects of EtOH withdrawal. The EtOH withdrawal syndrome has been shown to evoke a negative motivational state characterized by increased reward thresholds in animals and heightened EtOH self-administration in humans and animals. Research suggests that the amygdala and nucleus accumbens are associated with the motivational effects of withdrawal produced by opiate and stimulant dependence, and that both GABA and CRF systems are involved in the reinforcing aspects of EtOH dependence. Therefore the proposed research will utilize the intracranial self-stimulation (ICSS) reward threshold paradigm to assess the involvement of these neural and transmitter systems in the motivational aspects of EtOH dependence as measured by withdrawal.
Specific Aim 1 will assess the effects of ICV injections of the CRF antagonist D-Phe (12-41) or the GABA agonist muscrmol on the elevations in ICSS thresholds observed during EtOH withdrawal.
Specific Aim 2 will examine the effects of injections of these drugs into the amygdala or nucleus accumbens on EtOH withdrawal-induced elevations in ICSS thresholds. This research may more accurately determine the neural substrates of the negative motivational aspects of EtOH dependence, providing information critical to the treatment of alcohol abuse.
| Macey, D J; Froestl, W; Koob, G F et al. (2001) Both GABA(B) receptor agonist and antagonists decreased brain stimulation reward in the rat. Neuropharmacology 40:676-85 |
