RATIONALE: 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. MATERIALS AND 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). CONCLUSION: 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.
RATIONALE: 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. MATERIALS AND 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). CONCLUSION: 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.
Authors: Zheng-Ming Ding; Scott M Oster; Sheketha R Hauser; Jamie E Toalston; Richard L Bell; William J McBride; Zachary A Rodd Journal: J Pharmacol Exp Ther Date: 2011-10-19 Impact factor: 4.030
Authors: Zheng-Ming Ding; Scott M Oster; Sarah R Hall; Eric A Engleman; Sheketha R Hauser; William J McBride; Zachary A Rodd Journal: Psychopharmacology (Berl) Date: 2011-02-23 Impact factor: 4.530
Authors: Eric A Engleman; Cynthia M Ingraham; Zachary A Rodd; James M Murphy; William J McBride; Zheng-Ming Ding Journal: Drug Alcohol Depend Date: 2020-07-02 Impact factor: 4.492
Authors: Gerald A Deehan; Eric A Engleman; Zheng-Ming Ding; William J McBride; Zachary A Rodd Journal: Alcohol Clin Exp Res Date: 2012-12-20 Impact factor: 3.455
Authors: Gerald A Deehan; Christopher P Knight; R Aaron Waeiss; Eric A Engleman; Jamie E Toalston; William J McBride; Sheketha R Hauser; Zachary A Rodd Journal: Alcohol Alcohol Date: 2016-06-15 Impact factor: 2.826