Identification of the opioid receptor types mediating beta-endorphin-induced alterations in dopamine release in the nucleus accumbens.
In the present study we used in vivo microdialysis to examine the influence of beta-endorphin on dopamine (DA) release in the nucleus accumbens of anesthetized rats and to identify the opioid receptor types mediating its effects. Microdialysis probes were inserted into the nucleus accumbens and perfusates were analysed for DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using a reversed phase HPLC system with electrochemical detection for separation and quantification. Intracerebroventricular (i.c.v.) administration of beta-endorphin resulted in a dose-dependent increase in DA and its metabolites. Pretreatment with the selective delta-antagonist ICI 174,864 significantly attenuated the beta-endorphin-induced increase in DA release and metabolism whereas pretreatment with the selective mu-antagonist CTOP resulted abolition of the beta-endorphin effect. These data demonstrate that the blockade of either mu- or delta-opioid receptors is sufficient to antagonize the stimulatory effects of beta-endorphin on DA release and metabolism. As such, these findings suggest that the concomitant activation of both mu- and delta-receptors underlies the effects of beta-endorphin on DA release in the nucleus accumbens.
Spanagel
R
R
Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie, Martinsried, F.R.G.
Herz
A
A
Shippenberg
T S
TS
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology*
D000700:Analgesics; D015306:Biogenic Monoamines; D004745:Enkephalins; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D004298:Dopamine