Role of GABA B receptors in the endomorphin-1-, but not endomorphin-2-, induced dopamine efflux in the nucleus accumbens of freely moving rats.
In vivo microdialysis was used to study the effects of the locally applied GABA B receptor antagonist 2-hydroxysaclofen and GABA B receptor agonist baclofen on the basal dopamine efflux as well as on the endomorphin-1- and endomorphin-2-induced dopamine efflux in the nucleus accumbens of freely moving rats. 2-Hydroxysaclofen (100 and 500 nmol) increased basal dopamine efflux. Baclofen (2.5 and 5 nmol) failed to affect basal dopamine efflux. 2-Hydroxysaclofen (1 and 10 nmol) which did not alter the basal dopamine efflux, enhanced the endomorphin-1 (25 nmol)-induced dopamine efflux. Baclofen (2.5 and 5 nmol) failed to affect endomorphin-1 (25 nmol)-induced dopamine efflux, but it counteracted the 2-hydroxysaclofen-induced increase of the endomorphin-1-elicited dopamine efflux. Neither 2-hydroxysaclofen (10 nmol) nor baclofen (5 nmol) affected the endomorphin-2 (25 nmol)-induced dopamine efflux. The doses mentioned are the total amount of drug over the infusion period that varied across the drugs (25 or 50 min). These results suggest that accumbal GABA B receptor plays an inhibitory role on the basal as well as the endomorphin-1-elicited accumbal dopamine efflux. The present results support our earlier reported notion that endomorphin-1 and endomorphin-2 increase accumbal dopamine efflux by different mechanisms. Finally, it is suggested that a decrease of endogenous accumbal GABA reduces the accumbal GABA B receptor-mediated GABA-ergic inhibition, enhancing thereby the accumbal dopamine efflux.
Saigusa
Tadashi
T
Department of Pharmacology, Nihon University School of Dentistry, 1-8-13, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan. saigusa@dent.nihon-u.ac.jp
Aono
Yuri
Y
Mizoguchi
Naoko
N
Iwakami
Tomoyo
T
Takada
Koji
K
Oi
Yoshiyuki
Y
Ueda
Koichiro
K
Koshikawa
Noriaki
N
Cools
Alexander R
AR
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D018755:GABA Agonists; D018756:GABA Antagonists; D009842:Oligopeptides; D018080:Receptors, GABA-B; C105293:endomorphin 1; C105294:endomorphin 2; D001418:Baclofen; D004298:Dopamine; C057491:2-hydroxysaclofen