Behavioral effects of amantadine on ambulatory activity and drinking in mice and on continuous and discrete avoidance responses in rats

Abstract

Effects of amantadine on ambulatory activity in mice and conditioned avoidance responses in rats were investigated. In addition, the change in diurnal drinking rhythm induced by free intake of amantadine solution was also examined in mice. Amantadine (10-40 mg/kg, i.p.) tended to increase the ambulatory activity in mice. Pretreatment with amantadine (10-40 mg/kg, i.p.) at 30 minor 4 hr before augmented the ambulation-increasing effect of apomorphine (0.5 mg/kg, s.c.), but attenuated that of methamphetamine (2 mg/kg, s.c.). When amantadine solution of 0.1 mg/ml or 0.4 mg/ml was freely given to mice for 7 or 21 days, the amount of fluid intake per day decreased slightly, and the daily doses of amantadine intake were estimated to be 15-80 mg/kg/day. However, no marked change in the diurnal pattern of drinking, showing a higher rate during the dark period and a lower rate during the light period, was observed. These mice also demonstrated an increased sensitivity to the ambulation-increasing effect of apomorphine and a decreased sensitivity to that of methamphetamine as compared with the control mice that drank water with no added drugs. Amantadine (10-20 mg/kg, i.p.) did not induce a marked change in the avoidance responses in rats. However, more than 40 mg/kg, i.p. of amantadine suppressed the avoidance responses with a general worsening of bodily condition. Amantadine (10-20 mg/kg, i.p.) did not modify the avoidancefacilitating effects of methamphetamine (0.13-1 mg/kg, s.c.), atropine (1.3-10 mg/kg, s.c.) and scopolamine (0.031-0.13 mg/kg, s.c.), but attenuated the avoidance-suppressing effects of chlorpromazine (0.25-2 mg/kg, s.c.), haloperidol (0.018-0.05 mg/kg, s.c.), tetrabenazine (0.25-1 mg/kg, s.c.), pilocarpine (2-8 mg/kg, s.c.) and physostigmine (0.1-0.4 mg/kg, s.c.) in a dose-dependent manner. The present results suggest that amantadine affects not only the central catecholaminergic neurons but also the other neurons.