Involvement of 5-HT1B receptors within the ventral tegmental area in regulation of mesolimbic dopaminergic neuronal activity via GABA mechanisms: a study with dual-probe microdialysis.
This study was designed to assess the involvement of 5-HT1B receptors within the ventral tegmental area (VTA) in the regulation of mesolimbic dopaminergic transmission. 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). Drugs were administered into the VTA via retrograde dialysis. Dialysates from both the VTA and the NAC were collected for determination of dopamine (DA) and gamma-aminobutyric acid (GABA) by high-performance liquid chromatography with electrochemical detection. Intra-tegmental infusion of CP 93129 (20, 40, and 80 microM), a 5-HT1B receptor agonist, increased extracellular DA concentrations in a concentration-dependent manner not only in the NACC but also in the VTA, indicating increased mesolimbic DA neuron activity. Administration of CP 93129 at 80 microM into the VTA also significantly decreased extracellular GABA concentrations in this region. Co-infusion of the 5-HT1B receptor antagonist SB 216641 (10 microM), but not the 5-HT1A receptor antagonist WAY 100635 (10 microM) or the 5-HT1D/1A receptor antagonist BRL 15572 (10 microM), antagonized not only the effects of intra-tegmental CP 93129 (80 microM) on VTA DA and NAC DA but also on VTA GABA. The results suggest that activation of VTA 5-HT1B receptors increases mesolimbic DA neuron activities. The increased DA neuron activity may be associated, at least in part, with the 5-HT1B receptor-mediated inhibition of VTA GABA release.
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA. QSY@UIC.EDU
Qing-Shan
QS
Yan
Shi-Zhong
SZ
Zheng
Shu-E
SE
Yan
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways; D009474:Neurons / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001549:Benzamides; D001713:Biphenyl Compounds; D018755:GABA Agonists; 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; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D005680:gamma-Aminobutyric Acid; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D001418:Baclofen; C108532:BRL 15572; D004298:Dopamine