PMID- 1976759 OWN - NLM STAT- MEDLINE DCOM- 19901120 LR - 20220309 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 55 IP - 5 DP - 1990 Nov TI - The effects of opioid peptides on dopamine release in the nucleus accumbens: an in vivo microdialysis study. PG - 1734-40 AB - 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 mu-, delta-, and kappa- 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 mu-opioid [D-Ala2, N-methyl-Phe4, Gly5-ol]-enkephalin (DAMGO) or delta-opioid [D-Pen2, D-Pen5]-enkephalin (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 mu-antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) whereas those of DPDPE were blocked by the delta-antagonist allyl2-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864). In contrast to mu- and delta-agonists, the kappa-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. Norbinaltorphimine, a selective kappa-antagonist, could block this effect. These results demonstrate that mu-, delta-, and kappa-opioid agonists differentially affect DA release in the NAC and this action is centrally mediated. FAU - Spanagel, R AU - Spanagel R AD - Department of Neuropharmacology, Max-Planck-Institut fur Psychiatrie, Planegg-Martinsried, F.R.G. FAU - Herz, A AU - Herz A FAU - Shippenberg, T S AU - Shippenberg TS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Analgesics) RN - 0 (Endorphins) RN - 0 (Enkephalins) RN - 0 (Peptide Fragments) RN - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-) RN - 103613-84-9 (E 2078) RN - 4368-28-9 (Tetrodotoxin) RN - 74913-18-1 (Dynorphins) RN - 88373-73-3 (Enkephalin, D-Penicillamine (2,5)-) RN - I38ZP9992A (Magnesium) RN - RWP5GA015D (Potassium) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Analgesics/pharmacology MH - Animals MH - Dialysis/methods MH - Dopamine/*metabolism MH - Dynorphins/analogs & derivatives/pharmacology MH - Endorphins/*pharmacology MH - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- MH - Enkephalin, D-Penicillamine (2,5)- MH - Enkephalins/pharmacology MH - Injections, Intraventricular MH - Magnesium/pharmacology MH - Male MH - Nucleus Accumbens/*metabolism MH - Peptide Fragments/pharmacology MH - Potassium/pharmacology MH - Rats MH - Rats, Inbred Strains MH - Tetrodotoxin/pharmacology EDAT- 1990/11/01 00:00 MHDA- 1990/11/01 00:01 CRDT- 1990/11/01 00:00 PHST- 1990/11/01 00:00 [pubmed] PHST- 1990/11/01 00:01 [medline] PHST- 1990/11/01 00:00 [entrez] AID - 10.1111/j.1471-4159.1990.tb04963.x [doi] PST - ppublish SO - J Neurochem. 1990 Nov;55(5):1734-40. doi: 10.1111/j.1471-4159.1990.tb04963.x.