RT Journal Article
SR Electronic
T1 Dopamine Release in the Nucleus Accumbens during Heroin Self-Administration Is Modulated by <em>Kappa</em> Opioid Receptors: An <em>In Vivo</em> Fast-Cyclic Voltammetry Study
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 151
OP 161
VO 284
IS 1
A1 Zheng-Xiong Xi
A1 Scott A. Fuller
A1 Elliot A. Stein
YR 1998
UL http://jpet.aspetjournals.org/content/284/1/151.abstract
AB Mu and kappa opioid agonists are known to produce different, and sometimes opposite, effects on several pharmacological and behavioral measures. However, whetherkappa agonists can be used to antagonize the reinforcing and putative dopamine (DA)-releasing properties of a muagonist such as heroin is unclear. With the use of the high temporal and spatial resolution of in vivo fast-cyclic voltammetry to measure changes in extracellular DA in the nucleus accumbens (NAcc), we observed (1) dose-dependent increases in DA in the NAcc during heroin self-administration (SA), (2) that coadministration of the kappa agonist U50,488H with heroin or intracerebroventricular dynorphin A pretreatment significantly depressed the heroin-stimulated DA release during SA, where U50,488H alone inhibited the basal DA release in the NAcc, (3) that coadministration of low-dose U50,488H or dynorphin A significantly increased heroin SA behavior, whereas high-dose U50,488H, which alone did not support SA behavior, reduced or completely blocked heroin SA and (4) that nor-binaltorphimine dihydrochloride (a selectivekappa receptor antagonist) potentiated DA release in the NAcc and modestly decreased heroin SA. Taken together, these data suggest that endogenous kappa receptor activation can inhibit mu agonist-induced activation of the mesolimbic DA pathway, which may in turn depress heroin-induced reinforcement. The American Society for Pharmacology and Experimental Therapeutics