Verapamil effects on physiological and behavioral responses to ethanol in the rat

Experiments were performed to determine the ability of verapamil to reverse ethanol-induced hypothermia and behavioral changes. Permanent cannulae for intracerebroventricular (i.c.v.) infusion were implanted bilaterally in rats following standard stereotaxic procedures. Following post-operative recovery, either verapamil or artificial cerebral spinal fluid (ACSF) was infused i.c.v., followed by 4.0 g/kg ethanol in saline administered by intragastric gavage. Changes in body temperature and overall activity were monitored. In another series of experiments, rats were given either i.c.v. verapamil or ACSF followed by 1.5 g/kg intraperitoneal ethanol. Ability to turn over and open-field activity were monitored. In addition, to investigate the action of verapamil alone on body temperature, rats were infused i.c.v. either with verapamil or control ACSF, followed by intragastric administration of a volume of saline equal to 4.0 g/kg ethanol (20% v/v). At an ambient temperature of 22 degrees C, verapamil, infused prior to ethanol administration, significantly and rapidly attenuated the thermolytic action of ethanol. Central administration of verapamil alone did not induce a significant change in body temperature until more than 1.5 hr after injection, at which time temperature began to gradually increase. Pretreatment with verapamil induced significantly faster recovery from ethanol-induced changes in overall activity. Only a non-significant reversal of ethanol's effects on open-field activity and time taken to turn over occurred. These results demonstrate that verapamil can significantly antagonize ethanol-induced hypothermia and possibly motor disturbances in rats, leading us to postulate the possible involvement of neuronal Ca2+ channels in these effects of ethanol.