McBride W J, Murphy J M, Lumeng L, Li T K
Department of Psychiatry, R. L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202.
Pharmacol Biochem Behav. 1989 Oct;34(2):381-6. doi: 10.1016/0091-3057(89)90330-4.
The present study was undertaken to determine if spiroxatrine, a reported 5-HT1A antagonist, could block the attenuating effects of fluoxetine (a 5-HT uptake inhibitor) on voluntary ethanol intake by the selectively bred alcohol-preferring P line of rats. Fluoxetine (10 mg/kg, IP) significantly reduced the intake of 10% ethanol by P rats approximately 50% during the 4-hour period of alcohol availability. Spiroxatrine (4 mg/kg, IP) was without effect on ethanol intake when given alone. However, when given 5 minutes before fluoxetine (10 mg/kg, IP), this dose of spiroxatrine augmented the reduction of ethanol intake to approximately 15% of control values after 4 hours. Similar experiments conducted with 1 mg/kg (IP) 8-hydroxy-2(di-N-propylamino) tetralin (DPAT) demonstrated that this 5-HT1A agonist also enhanced the attenuating effects of fluoxetine on ethanol intake. Likewise, spiroxatrine augmented the DPAT reduction of alcohol intake. Spiroxatrine enhanced the effect of DPAT and fluoxetine on food intake as it did on ethanol intake. The results suggest that spiroxatrine behaved as a partial agonist and/or modulator and not as an antagonist at 5-HT1A receptors under the present experimental conditions.
本研究旨在确定已报道的5-羟色胺1A（5-HT1A）拮抗剂螺沙群是否能阻断氟西汀（一种5-羟色胺摄取抑制剂）对选择性培育的嗜酒P品系大鼠自愿乙醇摄入量的减弱作用。氟西汀（10毫克/千克，腹腔注射）在乙醇可获取的4小时期间，使P品系大鼠的10%乙醇摄入量显著减少了约50%。单独给予螺沙群（4毫克/千克，腹腔注射）对乙醇摄入量没有影响。然而，在给予氟西汀（10毫克/千克，腹腔注射）前5分钟给予该剂量的螺沙群，4小时后乙醇摄入量的减少增加到对照值的约15%。用1毫克/千克（腹腔注射）的8-羟基-2（二-N-丙基氨基）四氢萘（DPAT）进行的类似实验表明，这种5-HT1A激动剂也增强了氟西汀对乙醇摄入量的减弱作用。同样，螺沙群增强了DPAT对酒精摄入量的减少作用。螺沙群增强了DPAT和氟西汀对食物摄入量的作用，就如同其对乙醇摄入量的作用一样。结果表明，在当前实验条件下，螺沙群在5-HT1A受体上表现为部分激动剂和/或调节剂，而非拮抗剂。
