Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens.
The present study was undertaken to examine the involvement of activation of 5-HT3 receptors in the rat nucleus accumbens (Acb) on the effects of ethanol-induced increases of dopamine (DA) using the selective agonist 1-(m-chlorophenyl)-biguanide (CPBG). Perfusion of CPBG through the microdialysis probe concentration-dependently (3.3-100 microM) enhanced the extracellular levels of DA in the Acb. Extracellular DA concentrations increased as high as 1000% of baseline. The CPBG-induced increases in DA levels were Ca++ dependent and inhibited by local perfusion with the 5-HT3 antagonist ICS 205-930 (100 microM). In addition, CPBG at high concentrations caused significant decreases in the extracellular levels of DA metabolites. Intraperitoneal (IP) injection of 1 g/kg ethanol produced no changes in extracellular DA levels in the Acb; coadministration of 1 g/kg ethanol (IP) and 5 microM CPBG (local) produced increases equal to 5 microM CPBG alone. Administration of 2 g/kg ethanol (IP) alone enhanced extracellular DA levels by approximately 60% above baseline, whereas local perfusion of 5 microM CPBG alone produced an increase of approximately 100% above baseline. The coadministration of 2 g/kg ethanol (IP) and 5 microM CPBG (local) enhanced DA levels by approximately 170% above baseline; this apparent additive enhancement was almost completely prevented when 100 microM ICS 205-930 was locally coperfused. Local administration of 3.3-100 microM CPBG did not alter the extracellular levels of serotonin or 5-hydroxyindoleacetic acid. The results support an involvement of 5-HT3 receptors in regulating DA release in the Acb, and also in mediating ethanol-induced DA release.(ABSTRACT TRUNCATED AT 250 WORDS)
Campbell
A D
AD
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202-4887, USA.
McBride
W J
WJ
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D000431:Ethanol / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007211:Indoles / Q000494:pharmacology; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D001645:Biguanides; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000431:Ethanol; D000077526:Tropisetron; C065734:1-(3-chlorophenyl)biguanide; D002118:Calcium; D004298:Dopamine