Wellman Paul, Ho Dao, Cepeda-Benito Antonio, Bellinger Larry, Nation Jack
Department of Psychology, Texas A&M University, College Station, TX 77843-4235, USA.
Eur J Pharmacol. 2002 Nov 29;455(2-3):117-26. doi: 10.1016/s0014-2999(02)02616-x.
The present studies examined the effects of antagonizing alpha(1)-adrenoceptors via systemic administration of prazosin on the behavioral actions of cocaine in rats, including induction of locomotion and suppression of eating. In Experiment 1, locomotor activity was monitored in automated chambers for 80 min in adult male rats pretreated with the alpha(1)-adrenoceptor antagonist prazosin (0, 0.5, or 2 mg/kg, i.p.) and then treated (i.p.) with either 0, 10, 20, or 40 mg/kg cocaine hydrochloride. Cocaine dose-dependently increased total distance traveled and the number of stereotypy counts, and significantly decreased rest time. Each dose of prazosin produced a significant attenuation of the locomotor effects of a limited range of cocaine doses (i.e. 10 and/or 20 mg/kg cocaine, but not 40 mg/kg cocaine). Prazosin alone did not alter any measure of locomotion. In Experiment 2, eating and drinking were monitored for 60 min in male rats pretreated with prazosin (0, 1, and 2 mg/kg, i.p.) and then treated with 0, 10, 20, or 40 mg/kg (i.p.) cocaine. Rats pretreated with vehicle exhibited a dose-dependent suppression of eating, but not drinking, to cocaine. The impact of prazosin on cocaine-induced hypophagia paralleled that noted for locomotion in that administration of prazosin significantly attenuated the hypophagic action of 20 mg/kg cocaine, but not that of 40 mg/kg cocaine. These findings confirm earlier studies noting a partial role for alpha(1)-adrenoceptors in the locomotor stimulant actions of cocaine and extend those findings to the feeding-inhibitory actions of cocaine.
本研究通过对大鼠全身给予哌唑嗪拮抗α（1）-肾上腺素能受体，考察其对可卡因行为效应的影响，包括诱导运动和抑制进食。在实验1中，对成年雄性大鼠预先腹腔注射α（1）-肾上腺素能受体拮抗剂哌唑嗪（0、0.5或2mg/kg），然后腹腔注射0、10、20或40mg/kg盐酸可卡因，在自动箱中监测其运动活性80分钟。可卡因剂量依赖性地增加总行进距离和刻板行为计数，并显著减少休息时间。每剂哌唑嗪都能显著减弱一定剂量范围可卡因（即10和/或20mg/kg可卡因，但不是40mg/kg可卡因）的运动效应。单独使用哌唑嗪不会改变任何运动指标。在实验2中，对预先腹腔注射哌唑嗪（0、1和2mg/kg）的雄性大鼠监测进食和饮水60分钟，然后腹腔注射0、10、20或40mg/kg可卡因。预先注射赋形剂的大鼠对可卡因表现出剂量依赖性的进食抑制，但饮水不受影响。哌唑嗪对可卡因诱导的摄食减少的影响与对运动的影响相似，即给予哌唑嗪显著减弱20mg/kg可卡因的摄食减少作用，但不影响40mg/kg可卡因的作用。这些发现证实了早期研究中指出的α（1）-肾上腺素能受体在可卡因运动刺激作用中的部分作用，并将这些发现扩展到可卡因的进食抑制作用。
