期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 837, 期 -, 页码 88-95出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2018.08.003
关键词
GABA(B) receptor; Delta1-opioid receptor; Delta2-opioid receptor; Nucleus accumbens; Dopamine; Microdialysis
资金
- Japan Society for the Promotion of Science [18K09777, 17K11858]
- Nihon University Multidisciplinary Research Grant [SOH14-020, SOH15-017]
- Suzuki Fund from Nihon University School of Dentistry at Matsudo, Japan
- Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Japan
- Invitation Fellowships from the Japan Society for the Promotion of Science [S-12209, S-16093]
- Science Foundation Ireland International Strategic Cooperation Award [13/ISCA/2846]
- Grants-in-Aid for Scientific Research [18K09777, 17K11858] Funding Source: KAKEN
The nucleus accumbens contains delta-opioid receptors that may decrease inhibitory neurotransmission. As GABA(B) receptors inhibit dopamine release, decrease in activation of GABA(B) 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 GABA(B) receptors. As delta-opioid receptors are further subdivided into delta1- and delta2-opioid receptors, we analysed the effects of the GABA(B) 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 25-50 min infusions. Baclofen (2.5 and 5.0 nmol), which did not alter basal dopamine levels, inhibited the delta1-opioid receptor agonist DPDPE (5.0 nmol)-induced dopamine efflux. Baclofen (2.5 and 5.0 nmol) also inhibited the delta2-opioid receptor agonist deltorphin II (25.0 nmol)-induced dopamine efflux. A low dose of the GABA(B) receptor antagonist 2-hydroxysaclofen (100.0 pmol), which failed to alter basal accumbal dopamine levels, counteracted the inhibitory effects of baclofen (5.0 nmol) on DPDPE (5.0 nmol)- and deltorphin II (25.0 nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA(B) 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 GABA(B) receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux.
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