Involvement of local serotonin-2A but not serotonin-1B receptors in the reinforcing effects of ethanol within the posterior ventral tegmental area of female Wistar rats.
BACKGROUND
Previous studies indicated that ethanol could be self-infused into the posterior ventral tegmental area (p-VTA) and that activation of local serotonin-3 (5-HT(3)) receptors was involved. 5-HT(1B) and 5-HT(2A) receptors are involved in the effects of 5-HT and ethanol on VTA dopamine neurons.


OBJECTIVE
The current study used the intracranial self-administration (ICSA) procedure to determine the involvement of local 5-HT(1B) and 5-HT(2A) receptors in the self-infusion of ethanol into the p-VTA.


METHODS
Female Wistar rats were implanted unilaterally with a guide cannula aimed at the p-VTA. Seven days after surgery, rats were placed into the two-lever operant conditioning chambers for ICSA tests. The tests consisted of four acquisition sessions with self-infusion of 200 mg% ethanol alone, two or three sessions with co-infusion of the 5-HT(1B) antagonist GR 55562 (10, 100, or 200 microM) or the 5-HT(2A) antagonist R-96544 (10, 100, or 200 microM) with 200 mg% ethanol, and one final session with 200 mg% ethanol alone.


RESULTS
During the acquisition sessions, all rats readily self-infused ethanol and discriminated the active from inactive lever. Co-infusion of GR 55562, at all three doses, had no effect on the self-infusion of ethanol. In contrast, co-infusion of R-96544, at the two higher doses, attenuated responding on the active lever for ethanol infusion (p < 0.05).


CONCLUSIONS
The results suggest that the reinforcing effects of ethanol within the p-VTA are modulated, at least in part, by activation of local 5-HT(2A), but not 5-HT(1B), receptors.
Ding
Zheng-Ming
ZM
Graduate Program in Medical Neuroscience, Indiana University School of Medicine, Indianapolis, IN 46202, USA. zding@iupui.edu
Toalston
Jamie E
JE
Oster
Scott M
SM
McBride
William J
WJ
Rodd
Zachary A
ZA
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007262:Infusions, Intravenous; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D012054:Reinforcement, Psychology; D012646:Self Administration; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013238:Stereotaxic Techniques; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
C476157:(2R,4R)-4-hydroxy-2-(2-(2-(2-(3-methoxy)phenyl)ethyl)phenoxy)ethyl-1-methylpyrrolidine hydrochloride; D001549:Benzamides; D002492:Central Nervous System Depressants; D011725:Pyridines; D011759:Pyrrolidines; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; C103477:3-(3-(dimethylamino)propyl)-4-hydroxy-N-(4-(4-pyridinyl)phenyl)benzamide; D000431:Ethanol