Activation of serotonin-3 receptors increases dopamine release within the ventral tegmental area of Wistar and alcohol-preferring (P) rats.
The objectives of the present study were to (a) examine the effects of activating serotonin-3 (5-HT3) receptors on dopamine (DA) release in the anterior and posterior ventral tegmental area (VTA) of Wistar rats and (b) determine if there are differences in 5-HT3--stimulated DA release in the VTA between alcohol-preferring (P) and Wistar rats. Local perfusion with the 5-HT3 agonist 1-(m-chlorophenyl)-biguanide (CPBG) in the anterior and posterior VTA stimulated DA release in both the regions. The CPBG-stimulated increase in extracellular DA levels was significantly higher in the posterior than anterior VTA of Wistar rats. The basal extracellular DA levels were not significantly different between the anterior and posterior VTA of Wistar rats. However, the basal extracellular DA levels were significantly higher in the posterior VTA of Wistar rats than P rats. Local perfusion of CPBG into the posterior VTA stimulated somatodendritic DA release significantly more in the P than Wistar rat. Overall, the results indicate that there may be a heterogeneous distribution of functional 5-HT3 receptors within the VTA, with higher numbers in the posterior than anterior VTA, and that, compared to 5-HT3 receptors in Wistar rats, 5-HT3 receptors in the posterior VTA of P rats may be more responsive to stimulation.
Liu
Wen
W
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Thielen
Richard J
RJ
Rodd
Zachary A
ZA
McBride
William J
WJ
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D001645:Biguanides; D002492:Central Nervous System Depressants; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists; D000431:Ethanol; C065734:1-(3-chlorophenyl)biguanide; D004298:Dopamine