Schaefer G J, Holtzman S G
Pharmacol Biochem Behav. 1979 Jan;10(1):127-35. doi: 10.1016/0091-3057(79)90178-3.
Rats were implanted with bipolar stimulating electrodes aimed at the medial forebrain bundle of the lateral hypothalamus, and trained to press a lever in one of two different procedures in order to receive electrical stimulation through the electrodes. In a free-operant procedure, each response produced a 200 msec train of electric pulses at a suprathreshold current, the intensity of which remained constant throughout the session. In an auto-titration procedure, each response produced an electrical stimulus which was initially set at a suprathreshold intensity. Every 15th response reduced the stimulation current by 3 muA. The animal could reset the current to its initial intensity at any time by pressing a second lever in the test chamber. The average current at which the animal pressed the reset lever was defined as the reinforcement threshold. Dose-response functions were determined for d- and l-amphetamine, alpha-methyltyrosine, and haloperidol. The reinforcement threshold was decreased by both d- and l-amphetamine, increased by haloperidol, and not changed by alpha-methyltyrosine. These effects on reinforcement threshold were not consistently related to the drug-induced changes in response rate in either procedure. The auto-titration procedure may be useful for distinguishing between drugs which cause nonspecific changes in the rate of ongoing behavior and those which specifically modify the reinforcement efficacy of brain stimulation.
将双极刺激电极植入大鼠,电极目标为下丘脑外侧的内侧前脑束,并训练大鼠通过两种不同程序之一按压杠杆,以便通过电极接受电刺激。在自由操作程序中,每次反应会在阈上电流下产生200毫秒的电脉冲串,在整个实验过程中其强度保持恒定。在自动滴定程序中,每次反应会产生一个最初设定为阈上强度的电刺激。每第15次反应会使刺激电流降低3微安。动物可通过按压测试箱中的第二个杠杆随时将电流重置为初始强度。将动物按压重置杠杆时的平均电流定义为强化阈值。测定了右旋和左旋苯丙胺、α-甲基酪氨酸和氟哌啶醇的剂量-反应函数。右旋和左旋苯丙胺均降低强化阈值,氟哌啶醇提高强化阈值,而α-甲基酪氨酸不改变强化阈值。在这两种程序中,这些对强化阈值的影响与药物引起的反应率变化均无一致关联。自动滴定程序可能有助于区分引起持续行为速率非特异性变化的药物和那些特异性改变脑刺激强化效能的药物。