THE EFFECTS OF OPIOID-PEPTIDES ON DOPAMINE RELEASE IN THE NUCLEUS-ACCUMBENS - AN INVIVO MICRODIALYSIS STUDY

Abstract: An involvement of the mesolimbic dopamine (DA) system in mediating the motivational effects of opioids has been suggested. Accordingly, the present study employed the technique of in vivo microdialysis to examine the effects of selective μ‐, δ‐, and k‐ opioids on DA release in the nucleus accumbens (NAC) of anesthetized rats. Microdialysis probes were inserted into the NAC and perfusates were analyzed for DA and its metabolites, dihydroxyphenylacetic acid (DO‐PAC) and homovanillic acid (HVA), using a reverse‐phase HPLC system with electrochemical detection for separation and quantification. Intracerebroventricular (i.c.v.) administration of selective μ‐opioid [D‐Ala2, N‐methyl‐Phe4, Gly5‐ol]‐enkephalin (DAMGO) or δ‐opioid [d‐Pen2, d‐Pen5]‐en‐kephalin (DPDPE) agonists, at doses that function as positive reinforcers in rats, resulted in an immediate and significant increase in extracellular DA. DOPAC and HVA levels were also significantly increased. The effects of DAMGO were blocked by the selective μ‐antagonist d‐Pen‐Cys‐Tyr‐d‐Trp‐Orn‐Thr‐Pen‐Thr‐NH2 (CTOP) whereas those of DPDPE were blocked by the δ‐antagonist allyl2‐Tyr‐Aib‐Aib‐Phe‐Leu‐OH (ICI 174,864). In contrast to μ‐ and δ‐agonists, the k‐agonist N‐CH3‐Tyr‐Gly‐Gly‐Phe‐Leu‐Arg‐N‐CH3‐Arg‐d‐Leu‐NHC2H5 (E‐2078). a dynorphin analog that produces aversive states, decreased DA release in a biphasic manner. Norbin‐altorphimine, a selective k‐antagonist, could block this effect. These results demonstrate that μ‐, δ‐, and k‐opioid agonists differentially affect DA release in the NAC and this action is centrally mediated. Copyright © 1990, Wiley Blackwell. All rights reserved