Weiss F, Mitchiner M, Bloom F E, Koob G F
Research Institute of Scripps Clinic, Department of Neuropharmacology, La Jolla, CA 92037.
Psychopharmacology (Berl). 1990;101(2):178-86. doi: 10.1007/BF02244123.
The role of opioids, dopamine and serotonin in ethanol (EtOH) reward and preference was investigated in non-deprived, Alcohol-Preferring (P), and genetically heterogenous Wistar rats. Operant responding for ethanol was initiated using sweet-solution substitution procedures. The rats were then trained in 30-min daily sessions to respond for ethanol (10% v/v) versus water under a two-lever, free-choice contingency. All testing was conducted in the absence of water and food deprivation or addition of sweeteners to the ethanol drinking solution. Rats of both strains developed stable preferences in responding for ethanol over water and consumed ethanol at quantities sufficient to produce pharmacologically relevant mean blood alcohol concentrations (P-Rats: 98 +/- 19.6 mg%; unselected Wistars: 41.7 +/- 8.5 mg%). In P-rats, systemic naloxone (NAL; 0.125, 0.25 and 0.5 mg/kg) pretreatments resulted in a dose-dependent suppression in responding for both ethanol and water, but did not alter ethanol preference (expressed as percent ethanol of total intake). In contrast, bromocriptine (BRO; 1.0, 2.0 and 4.0 mg/kg) produced a significant, dose-dependent shift in preference from ethanol toward water by inhibiting responding for ethanol while enhancing water consumption. In unselected Wistar rats, NAL and BRO treatments produced changes in ethanol preference patterns similar to those observed in P-rats. However, compared to P-rats, these changes were smaller and not consistently dose dependent. No changes in ethanol preference and water or ethanol intake were observed with methysergide (MET; 2.5, 5.0, 10.0 mg/kg) in either strain of rat. Together, the results suggest a possible involvement of dopaminergic mechanisms in the reinforcing properties of ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
在未禁食的嗜酒(P)大鼠和基因异质的Wistar大鼠中,研究了阿片类物质、多巴胺和5-羟色胺在乙醇(EtOH)奖赏和偏好中的作用。采用甜味溶液替代程序启动对乙醇的操作性反应。然后,大鼠每天接受30分钟的训练,在双杠杆自由选择条件下对乙醇(10% v/v)和水做出反应。所有测试均在不剥夺水和食物或在乙醇饮用溶液中添加甜味剂的情况下进行。两种品系的大鼠对乙醇的反应均形成了稳定的偏好,且摄入的乙醇量足以产生具有药理学相关性的平均血液酒精浓度(P大鼠:98±19.6 mg%;未选择的Wistar大鼠:41.7±8.5 mg%)。在P大鼠中,全身性纳洛酮(NAL;0.125、0.25和0.5 mg/kg)预处理导致对乙醇和水的反应呈剂量依赖性抑制,但未改变乙醇偏好(以总摄入量中乙醇的百分比表示)。相比之下,溴隐亭(BRO;1.0、2.0和4.0 mg/kg)通过抑制对乙醇的反应同时增加水的消耗,使偏好从乙醇向水发生了显著的、剂量依赖性的转变。在未选择的Wistar大鼠中,NAL和BRO处理产生的乙醇偏好模式变化与在P大鼠中观察到的相似。然而,与P大鼠相比,这些变化较小且并非始终呈剂量依赖性。在两种品系的大鼠中,麦角新碱(MET;2.5、5.0、10.0 mg/kg)均未观察到乙醇偏好、水或乙醇摄入量的变化。总之,结果表明多巴胺能机制可能参与了乙醇的强化特性。(摘要截断于250字)