Stimulation of accumbal GABAA receptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats

Yuri Aono; Yuri Kiguchi; Yuriko Watanabe; John L Waddington; Tadashi Saigusa

doi:10.1016/j.ejphar.2017.09.019

Stimulation of accumbal GABA_A receptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats

Eur J Pharmacol. 2017 Nov 15:815:18-25. doi: 10.1016/j.ejphar.2017.09.019. Epub 2017 Sep 18.

Authors

Yuri Aono¹, Yuri Kiguchi², Yuriko Watanabe³, John L Waddington⁴, Tadashi Saigusa⁵

Affiliations

¹ Department of Pharmacology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
² Department of Pediatric Dentistry, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
³ Department of Oral surgery, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
⁴ Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland.
⁵ Department of Pharmacology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan. Electronic address: saigusa.tadashi@nihon-u.ac.jp.

PMID: 28923348
DOI: 10.1016/j.ejphar.2017.09.019

Abstract

The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABA_A receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABA_A receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABA_A receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were administered intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 25-50min infusions. The delta2-opioid receptor agonist deltorphin II (25.0nmol)- and delta1-opioid receptor agonist DPDPE (5.0nmol)-induced increases in dopamine efflux were inhibited by the delta2-opioid receptor antagonist naltriben (1.5nmol) and the delta1-opioid receptor antagonist BNTX (150.0pmol), respectively. Muscimol (250.0pmol) inhibited deltorphin II (25.0nmol)-induced dopamine efflux. The GABA_A receptor antagonist bicuculline (50.0pmol), which failed to affect deltorphin II (25.0nmol)-induced dopamine efflux, counteracted the inhibitory effect of muscimol on deltorphin II-induced dopamine efflux. Neither muscimol (250.0pmol) nor bicuculline (50.0 and 500.0pmol) altered DPDPE (5.0nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA_A receptor-mediated inhibition of dopaminergic activity is necessary to produce delta2-opioid receptor-induced increase in accumbal dopamine efflux. This study indicates that activation of delta2- but not delta1-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA_A receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux.

Keywords: Delta1-opioid receptor; Delta2-opioid receptor; Dopamine; GABA(A) receptor; Microdialysis; Nucleus accumbens.

MeSH terms

Animals
Bicuculline / pharmacology
Biological Transport / drug effects
Dopamine / metabolism*
Extracellular Space / drug effects
Extracellular Space / metabolism
GABA-A Receptor Agonists / pharmacology
GABA-A Receptor Antagonists / pharmacology
Male
Movement*
Muscimol / pharmacology
Nucleus Accumbens / drug effects*
Nucleus Accumbens / metabolism*
Oligopeptides / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, GABA-A / metabolism*
Receptors, Opioid, delta / antagonists & inhibitors*

Substances

GABA-A Receptor Agonists
GABA-A Receptor Antagonists
Oligopeptides
Receptors, GABA-A
Receptors, Opioid, delta
deltorphin II, Ala(2)-
Muscimol
Dopamine
Bicuculline