Maccioni Paola, Fantini Noemi, Froestl Wolfgang, Carai Mauro A M, Gessa Gian Luigi, Colombo Giancarlo
C.N.R. Institute of Neuroscience, Cagliari, Italy.
Alcohol Clin Exp Res. 2008 Sep;32(9):1558-64. doi: 10.1111/j.1530-0277.2008.00725.x. Epub 2008 Jul 9.
Activation of the GABA(B) receptor--either by means of direct agonists (like baclofen) or positive allosteric modulators (like GS39783)--has been observed to suppress alcohol drinking and reinforcement in rats and mice. The present study was conducted to assess and compare the effect of baclofen and GS39783 on the motivational properties of alcohol.
Selectively bred Sardinian alcohol-preferring (sP) rats were initially trained to respond on a lever (on an fixed ratio 4 schedule of reinforcement) to orally self-administer alcohol (15%, v/v) or sucrose (3%, w/v) in daily 30-minute sessions. Once lever-responding reached stable levels, rats were exposed to sessions with a progressive ratio schedule of reinforcement. The effect of nonsedative doses of baclofen (0, 1, and 3 mg/kg, i.p.) and GS39783 (0, 25, 50, and 100 mg/kg, i.g.) on breakpoint for alcohol and sucrose (defined as the lowest response requirement not achieved by each rat and used as index of the motivational strength of alcohol and sucrose) was determined.
Baclofen administration resulted in a dose-dependent decrease in breakpoint for alcohol; this effect was not specific, as baclofen also reduced--to a comparable extent--breakpoint for sucrose. Conversely, GS39783 administration resulted in a dose-dependent and completely specific reduction in breakpoint for alcohol.
The present results (i) confirm previous data on baclofen's capacity to suppress, although nonspecifically, alcohol's motivational properties, and (ii) extend to alcohol's motivational properties the capacity of GS39783 to inhibit alcohol drinking and reinforcement in rats.
已观察到，通过直接激动剂（如巴氯芬）或正变构调节剂（如GS39783）激活GABA(B)受体可抑制大鼠和小鼠的酒精摄入及强化作用。本研究旨在评估和比较巴氯芬与GS39783对酒精动机特性的影响。
选用选择性培育的撒丁岛嗜酒（sP）大鼠，最初训练它们在杠杆上做出反应（按固定比率4强化程序），以便在每天30分钟的实验时段内口服自行摄入酒精（15%，v/v）或蔗糖（3%，w/v）。一旦杠杆反应达到稳定水平，大鼠就会接受采用累进比率强化程序的实验时段。测定非镇静剂量的巴氯芬（0、1和3毫克/千克，腹腔注射）和GS39783（0、25、50和100毫克/千克，灌胃）对酒精和蔗糖断点（定义为每只大鼠未达到的最低反应要求，用作酒精和蔗糖动机强度指标）的影响。
给予巴氯芬导致酒精断点呈剂量依赖性降低；这种效应不具有特异性，因为巴氯芬也会在相当程度上降低蔗糖断点。相反，给予GS39783导致酒精断点呈剂量依赖性且完全特异性降低。
本研究结果（i）证实了先前关于巴氯芬抑制酒精动机特性能力的非特异性数据，（ii）将GS39783抑制大鼠酒精摄入及强化作用的能力扩展至酒精的动机特性。
