Kiianmaa K, Tuomainen P, Makova N, Seppä T, Mikkola J A, Petteri Piepponen T, Ahtee L, Hyytiä P
Department of Mental Health and Alcohol Research, National Public Health Institute, POB 719, 00101, Helsinki, Finland.
Eur J Pharmacol. 2000 Nov 3;407(3):293-302. doi: 10.1016/s0014-2999(00)00759-7.
The aim of the study was to investigate the importance of the interaction between central dopaminergic and cholinergic mechanisms for ethanol reinforcement. This was done by comparing the effects of nicotine on locomotor activity and release of dopamine in the nucleus accumbens of the alcohol-preferring Alko Alcohol (AA) and alcohol-avoiding alko non-alcohol (ANA) rats. Nicotine was administered acutely (0.25, 0.50 or 0.75 mg/kg, s.c.) or repeatedly once daily (0.5 mg/kg, s.c.) for 8 days. An acute dose of nicotine increased locomotor activity and the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) measured with in vivo microdialysis suggesting stimulation of dopamine release by nicotine. No difference in the stimulation of locomotor activity or in the increase in the extracellular concentrations of dopamine or its metabolites by nicotine was found between the rat lines. The concentrations of nicotine in the plasma were also identical. The rats treated repeatedly with nicotine showed a progressive increase in locomotion. On the challenge day, 1 week after termination of nicotine or saline injections, rats previously treated with nicotine were activated more by nicotine than saline-treated rats. This behavioral sensitization was not accompanied by an increase in the amplitude of the neurochemical response to nicotine, but the duration of the increase in the levels of DOPAC was longer in the nicotine than saline-treated animals. The increases in locomotor activity and metabolite levels were, however, similar in both rat lines. These data suggest that differences in the interaction of central dopaminergic and cholinergic mechanisms probably do not contribute to the difference in ethanol self-administration between the AA and ANA rat lines.
本研究的目的是调查中枢多巴胺能和胆碱能机制之间的相互作用对乙醇强化作用的重要性。通过比较尼古丁对嗜酒的阿尔科酒精（AA）大鼠和避酒的阿尔科非酒精（ANA）大鼠伏隔核中运动活性和多巴胺释放的影响来实现这一目的。尼古丁通过皮下注射急性给药（0.25、0.50或0.75毫克/千克）或每天重复给药一次（0.5毫克/千克，皮下注射），持续8天。急性剂量的尼古丁增加了运动活性以及通过体内微透析测量的多巴胺、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的细胞外水平，表明尼古丁刺激了多巴胺释放。在这两种大鼠品系之间，未发现尼古丁对运动活性的刺激或对多巴胺及其代谢产物细胞外浓度增加的差异。血浆中的尼古丁浓度也相同。反复用尼古丁处理的大鼠运动逐渐增加。在停药日，即尼古丁或生理盐水注射终止1周后，先前用尼古丁处理的大鼠对尼古丁的反应比用生理盐水处理的大鼠更活跃。这种行为敏化并未伴随着对尼古丁神经化学反应幅度的增加，但在尼古丁处理的动物中，DOPAC水平增加的持续时间比生理盐水处理的动物更长。然而，在两种大鼠品系中，运动活性和代谢产物水平的增加是相似的。这些数据表明，中枢多巴胺能和胆碱能机制相互作用的差异可能不会导致AA和ANA大鼠品系在乙醇自我给药方面的差异。
