Czachowski Cristine L
Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island 02912, USA.
Alcohol Clin Exp Res. 2005 Jul;29(7):1146-55. doi: 10.1097/01.alc.0000171944.50381.86.
Behaviorally relevant stimuli, including alcohol, are processed through the nucleus accumbens/ventral tegmental area (VTA)/prefrontal cortex circuit. It is hypothesized that serotonin affects ethanol-directed behaviors by interacting with this system via projections from the dorsal raphe to the nucleus accumbens and VTA. The current studies utilized two different operant paradigms, one focusing on reinforcer seeking and one focusing on reinforcer self-administration (both with an ethanol and a sucrose solution as the reinforcer) to elucidate serotonin-specific regulation of these behaviors.
The present experiments assessed the effects of microinjections of a serotonin1B agonist (CGS12066B) and a serotonin1A agonist (8-OH-DPAT) in the nucleus accumbens core on ethanol- and sucrose-reinforced seeking and intake. In four separate experiments, male Long-Evans rats were trained to complete a single response requirement that resulted in access to 10% ethanol or 2% sucrose for a 20-min drinking period.
Before microinjections, ethanol-reinforced subjects were consuming an average of 0.5-0.95 g/kg ethanol and making 50-100 responses during intermittent nonreinforced sham (no drug) sessions (sucrose groups had similar baseline response levels). In summary, findings from the four experiments showed the following: (1) manipulations of serotonin function that had effects on ethanol-reinforced responding had either no effect or less pronounced effects on sucrose-reinforced responding; (2) administration of the serotonin1B agonist decreased seeking behaviors to a greater degree than drinking behaviors; and (3) administration of the serotonin1A agonist decreased ethanol intake but not seeking with no impact at all on sucrose-reinforced behaviors.
Manipulations of serotonin activity in the nucleus accumbens core had little effect on sucrose-reinforced behaviors and differential effects on ethanol seeking versus intake, suggesting that this area may play a complex but selective role in the stimulus processing of external and internal alcohol-associated cues.
包括酒精在内的与行为相关的刺激通过伏隔核/腹侧被盖区（VTA）/前额叶皮质回路进行处理。据推测，血清素通过从背侧中缝核到伏隔核和VTA的投射与该系统相互作用，从而影响与乙醇相关的行为。当前的研究采用了两种不同的操作性范式，一种侧重于强化物寻求，另一种侧重于强化物自我给药（均以乙醇和蔗糖溶液作为强化物），以阐明血清素对这些行为的特异性调节。
本实验评估了在伏隔核核心微量注射血清素1B激动剂（CGS12066B）和血清素1A激动剂（8-OH-DPAT）对乙醇和蔗糖强化的寻求及摄取行为的影响。在四个独立实验中，雄性Long-Evans大鼠接受训练，以完成单一反应要求，从而在20分钟的饮水期内获得10%乙醇或2%蔗糖。
在微量注射前，乙醇强化组的大鼠在间歇性无强化的假注射（无药物）期间平均消耗0.5 - 0.95克/千克乙醇，并做出50 - 100次反应（蔗糖组有相似的基线反应水平）。总之, 四项实验的结果表明：（1）对血清素功能的操纵若对乙醇强化反应有影响，那么对蔗糖强化反应要么无影响，要么影响较小；（2）血清素1B激动剂的给药对寻求行为的降低程度大于对饮用行为的降低程度；（3）血清素1A激动剂的给药减少了乙醇摄取，但不影响寻求行为，且对蔗糖强化行为完全没有影响。
伏隔核核心中血清素活性操作对蔗糖强化行为影响很小，对乙醇寻求和摄取有不同影响，这表明该区域可能在外部和内部酒精相关线索的刺激处理中发挥复杂但选择性的作用。
