Stimulation of accumbal GABAB receptors inhibits delta1- and delta2-opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats.
Eur J Pharmacol
; 837: 88-95, 2018 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-30086266
ABSTRACT
The nucleus accumbens contains delta-opioid receptors that may decrease inhibitory neurotransmission. As GABAB receptors inhibit dopamine release, decrease in activation of GABAB receptors may be a mediator of delta-opioid receptor-induced accumbal dopamine efflux. If so, accumbal dopamine efflux induced by delta-opioid receptor activation should be suppressed by stimulating GABAB receptors. As delta-opioid receptors are further subdivided into delta1- and delta2-opioid receptors, we analysed the effects of the GABAB receptor agonist baclofen on delta1- and delta2-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds show total amount administered (mol) during 25-50â¯min infusions. Baclofen (2.5 and 5.0â¯nmol), which did not alter basal dopamine levels, inhibited the delta1-opioid receptor agonist DPDPE (5.0â¯nmol)-induced dopamine efflux. Baclofen (2.5 and 5.0â¯nmol) also inhibited the delta2-opioid receptor agonist deltorphin II (25.0â¯nmol)-induced dopamine efflux. A low dose of the GABAB receptor antagonist 2-hydroxysaclofen (100.0â¯pmol), which failed to alter basal accumbal dopamine levels, counteracted the inhibitory effects of baclofen (5.0â¯nmol) on DPDPE (5.0â¯nmol)- and deltorphin II (25.0â¯nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABAB receptor-mediated inhibition of accumbal dopaminergic activity facilitates activation of delta1- and delta2-opioid receptor-induced increases in accumbal dopamine efflux. This study suggests that activation of delta1- and delta2-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABAB receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dopamina
/
Receptores de GABA-B
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Receptores Opioides delta
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Núcleo Accumbens
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón