The goal of this proposal is to determine the role of norepinephrine(NE) in the expression of opiate withdrawal (OW) behaviors. It has been demonstrated that the NAcc is significantly involved in mediating the somatic and aversive effects of OW. Other studies have shown that DA levels are decreased in the NAcc during OW. Furthermore, there is abundant evidence to suggest that the locus coeruleus (LC), a major component of the noradrenergic , becomes overactive during OW. Recent anatomical studies have demonstrated dense innervation of the NAcc by dopamine-beta-hydroxylase (DBH)-containing fibers suggesting a possible site of interaction between DA and NE. We hypothesize that prolonged release of NE, resulting from overactivity of the LC, amy contribute to the OW-induced decrease in DA in the NAcc and the behavioral effects of OW. Interference with NE neurotransmission in the NAcc may attenuate the decrease in DA and thus, the expression of OW behaviors. The experiments proposed in this application will specify the extent and source a DbetaH fiber innervation of the NAcc using anatomical techniques. Additional experiments will examine the effects of local microinjection of NE agents into the NAcc on the expression of OW behaviors. A greater understanding of how these neurotransmitter systems interact in the expression of withdrawal symptoms may lead to the development of better therapeutic agents for the treatment of OW in human addicts.
