平多洛
内分泌学
内科学
兴奋剂
化学
乙醇
部分激动剂
5-HT1A受体
敌手
受体
神经递质
血清素
药理学
5-羟色胺受体
医学
生物化学
作者
Omkar L. Patkar,Arnauld Belmer,Joan Holgate,Paul M. Klenowski,Selena E. Bartlett
摘要
Abstract Repeated cycles of binge‐like alcohol consumption and abstinence change the activity of several neurotransmitter systems. Some of these changes are consolidated following prolonged alcohol use and are thought to play an important role in the development of dependence. We have previously shown that systemic administration of the dual beta‐adrenergic antagonist and 5‐HT 1A/1B partial agonist pindolol selectively reduces long‐term but not short‐term binge‐like consumption of ethanol and alters excitatory postsynaptic currents in basolateral amygdala (BLA) principal neurons. The aim of this study was to investigate the effects of pindolol microinfusions in the BLA on long‐term ethanol intake using the drinking‐in‐the‐dark paradigm in mice. We also microinfused RU24969 (5‐HT 1A/1B receptor partial agonist) and CGP12177 (β 1/2 adrenergic antagonist) following long‐term ethanol intake and determined the densities of 5‐HT 1A/1B receptors and β 1/2 adrenergic in the BLA following short‐term (4 weeks) and long‐term ethanol (12 weeks) consumption. We show that intra‐BLA infusion of pindolol (1000 pmol/0.5 μl), RU24969 (0.3 and 3 pmol/0.5 μl) and CGP12177 (500 pmol/0.5 μl) produce robust decreases in long‐term ethanol consumption. Additionally, we identified reduced β 1/2 adrenergic receptor expression and no change in 5‐HT 1A/1B receptor density in the BLA of long‐term ethanol‐consuming mice. Collectively, our data highlight the effects of pindolol on voluntary, binge‐like ethanol consumption behavior following long‐term intake.
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