The reinforcing actions of a serotonin-3 receptor agonist within the ventral tegmental area: evidence for subregional and genetic differences and involvement of dopamine neurons.
Studies from our laboratory indicated that local perfusion of the ventral tegmental area (VTA) with a serotonin-3 (5-HT(3)) receptor agonist increased dopamine (DA) neuronal activity and that the self-infusion of ethanol (EtOH) and cocaine into the posterior VTA could be inhibited with coadministration of a 5-HT(3) receptor antagonist. The study tested the hypothesis that activating 5-HT(3) receptors within the VTA produces reinforcing effects. The study also examined whether there were differences between Wistar rats and a line of rats selectively bred for high alcohol consumption with regard to the self-infusion of a 5-HT(3) receptor agonist within the VTA. Adult female alcohol-preferring (P) and Wistar rats were allowed to self-infuse the 5-HT(3) receptor agonist 1-(m-chlorophenyl)-biguanide (CPBG) into the posterior or anterior VTA. Furthermore, experiments examined the effects of coinfusion of the 5-HT(3) antagonist ICS 205,930 (ICS), and the DA D(2,3) agonist quinpirole on the self-infusion of CPBG. Both Wistar and P rats readily self-administered CPBG into the posterior, but not anterior, VTA. P rats self-infused lower concentrations of CPBG (0.10 microM) than did Wistar rats (1.0 microM). Coinfusion of either ICS or quinpirole reduced CPBG self-infusion into the posterior VTA. The results of this study suggest that activation of 5-HT(3) receptors within the posterior VTA produces reinforcing effects and that these reinforcing effects are mediated through activation of DA neurons. Furthermore, the data suggest that selective breeding for alcohol-preference results in the posterior VTA being more sensitive to the reinforcing effects of CPBG.
Rodd
Zachary A
ZA
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA. zrodd@iupui.edu
Gryszowka
Victoria E
VE
Toalston
Jamie E
JE
Oster
Scott M
SM
Ji
Dong
D
Bell
Richard L
RL
McBride
William J
WJ
D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology; D000818:Animals; D001645:Biguanides / Q000008:administration & dosage / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000737:chemistry; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007263:Infusions, Parenteral; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000379:methods / Q000523:psychology; D058827:Serotonin 5-HT3 Receptor Agonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000077526:Tropisetron; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D001645:Biguanides; D018491:Dopamine Agonists; D007211:Indoles; D058827:Serotonin 5-HT3 Receptor Agonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D019257:Quinpirole; D000077526:Tropisetron; C065734:1-(3-chlorophenyl)biguanide; D004298:Dopamine