Nowak K L, McBride W J, Lumeng L, Li T K, Murphy J M
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, USA.
Alcohol Clin Exp Res. 2000 Apr;24(4):476-83.
The ventral tegmental area (VTA) dopamine (DA) system is considered to be involved in mediating the actions of ethanol (EtOH). The objective of the present study was to examine the role of VTA DA D2 receptors in regulating EtOH intake of alcohol-preferring P rats.
EtOH (10% v/v) and saccharin (SACC, 0.0125% g/v) intake during 2 hr of limited access was assessed after microinjections of the D2 agonist quinpirole and the D2 antagonist sulpiride into the anterior VTA (AVTA) of female P rats. Both EtOH-SACC alternate-day-access conditions and daily availability of EtOH and SACC solutions to separate groups of subjects were used. A second D2 agonist, quinelorane, and coadministration of 2.0 microg sulpiride with 2.0 microg quinpirole were tested in animals given limited access to EtOH. Finally, the effects of quinpirole injected 2 mm dorsal to the VTA and within the posterior VTA (PVTA) were assessed under EtOH-SACC alternate-day-access conditions.
Microinjections of 2.0-6.0 microg quinpirole into the AVTA dose dependently decreased EtOH intake 40-80% during the first 30 min of the limited access sessions but did not alter SACC intake. Injections of 2.0-4.0 microg quinelorane into the AVTA also reduced EtOH intake in the first 30 min. Administration of 0.5-2.0 microg sulpiride into the AVTA had no effect on either EtOH or SACC intakes but did attenuate the effects of quinpirole on reducing EtOH intake. Injections of 2.0-4.0 quinpirole 2 mm dorsal to the VTA did not alter EtOH or SACC intakes. Posterior VTA injections of quinpirole decreased EtOH and SACC intakes approximately 25-30% and 60-70%, respectively, in the first 30 min. None of the treatments altered intakes during the 30-120 min period.
The data suggest that DA neuronal activity within the AVTA may be important for maintaining EtOH drinking in P rats, whereas DA neuronal activity within the PVTA may be involved in regulating general drinking and/or motivational behaviors. Overall, the results confirm the involvement of mesolimbic DA in EtOH self-administration and suggest that there is functional heterogeneity within the VTA regulating drinking behavior of the P rat.
腹侧被盖区（VTA）多巴胺（DA）系统被认为参与介导乙醇（EtOH）的作用。本研究的目的是研究VTA DA D2受体在调节偏爱酒精的P大鼠乙醇摄入量中的作用。
在向雌性P大鼠的前VTA（AVTA）微量注射D2激动剂喹吡罗和D2拮抗剂舒必利后，评估了有限接触2小时期间乙醇（10% v/v）和糖精（SACC，0.0125% g/v）的摄入量。采用了乙醇-糖精隔日接触条件以及将乙醇和糖精溶液每日提供给不同组别的受试者这两种方式。在给予有限接触乙醇的动物中测试了另一种D2激动剂喹氯雷以及2.0微克舒必利与2.0微克喹吡罗的联合给药。最后，在乙醇-糖精隔日接触条件下评估了在VTA背侧2毫米处和后VTA（PVTA）内注射喹吡罗的效果。
向AVTA微量注射2.0 - 6.0微克喹吡罗在有限接触期的前30分钟内剂量依赖性地使乙醇摄入量减少40 - 80%，但不改变糖精摄入量。向AVTA注射2.0 - 4.0微克喹氯雷在最初30分钟内也减少了乙醇摄入量。向AVTA给予0.5 - 2.0微克舒必利对乙醇或糖精摄入量均无影响，但确实减弱了喹吡罗对减少乙醇摄入量的作用。在VTA背侧2毫米处注射2.0 - 4.0微克喹吡罗不改变乙醇或糖精摄入量。在后VTA注射喹吡罗在最初30分钟内分别使乙醇和糖精摄入量减少约25 - 30%和60 - 70%。在30 - 120分钟期间，所有处理均未改变摄入量。
数据表明，AVTA内的DA神经元活动可能对维持P大鼠的乙醇饮用很重要，而PVTA内的DA神经元活动可能参与调节一般饮用和/或动机行为。总体而言，结果证实了中脑边缘DA参与乙醇自我给药，并表明VTA内存在调节P大鼠饮用行为的功能异质性。
