Involvement of 5-HT1B receptors within the ventral tegmental area in ethanol-induced increases in mesolimbic dopaminergic transmission.
Evidence suggests that 5-hydroxytriptamine-1B (5-HT1B) receptors play a role in modifying ethanol's reinforcing effects and voluntary intake, and that 5-HT1B receptors within the ventral tegmental area (VTA) are involved in regulation of mesolimbic dopaminergic neuronal activity. Since increased mesolimbic dopaminergic transmission has been implicated in ethanol's reinforcing properties, this study was designed to assess the involvement of VTA 5-HT1B receptors in mediating the stimulatory effects of ethanol on VTA dopaminergic neurons. Dual-probe microdialysis was performed in freely moving adult Sprague-Dawley rats with one probe within the VTA and the other within the ipsilateral nucleus accumbens (NACC). Dopamine (DA) levels in dialysates from both areas, as the index of the activity of mesolimbic DA neurons, were measured simultaneously. The results showed that intraperitoneal injection of ethanol at the doses of 1 and 2 g/kg increased extracellular DA concentrations in both the VTA and the NACC, suggesting increased DA neuronal activity. These ethanol-induced increases of the DA release in the VTA and the NACC were significantly attenuated by intra-tegmental infusion of SB 216641 (a 5-HT(1B) receptor antagonist), but not BRL 15572 (a 5-HT(1D/1A) receptor antagonist) or WAY 100635 (a 5-HT1A receptor antagonist). Administration of ethanol at the same doses did not significantly alter extracellular levels of GABA in the VTA. The results also showed that intra-tegmental infusion of CP 94253, a 5-HT1B receptor agonist, significantly prolonged the effects of ethanol on NACC DA. The results suggest that blockade and activation of VTA 5-HT1B receptors attenuates and potentiates the neurochemical effects of ethanol, respectively, and support the suggestion that VTA 5-HT(1B) receptors may be involved in part in mediating the activating effects of ethanol on mesolimbic DA neurons.
Yan
Qing-Shan
QS
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, IL 61656, USA. QSY@UIC.EDU
Zheng
Shi-Zhong
SZ
Feng
Mei-Jiang
MJ
Yan
Shu-E
SE
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage; D001713:Biphenyl Compounds / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010069:Oxadiazoles / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001549:Benzamides; D001713:Biphenyl Compounds; C097067:CP 94253; C108531:N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; C108532:BRL 15572; D004298:Dopamine