Circadian Variation of Nicotine-Induced Ambulatory Activity in Rats

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Abstract
Circadian variation of nicotine-induced ambulatory activity in drug-naive rats was investigated. To test ambulatory activity, male Wistar rats (4 weeks of age) housed under a 12 hr light-dark cycle (light on from 6:00 to 18:00) with dawn and dusk periods (each over 2 hr), for 25 days, were injected with nicotine (0.1 or 0.5 mg/kg) at one of six times each day (2:00, 6:00, 10:00, 14:00, 18:00 and 22:00). These activities were recorded with an Ambulo-meter for 120 min immediately after subcutaneous injection of nicotine or 0.9% NaCl solution (saline). A large dose of nicotine (0.5 mg/kg) depressed the ambulatory activity and induced ataxia during the first 20 min, but the activity increased later in the test session at all times of the day. On the other hand, a small dose of nicotine (0.1 mg/kg) depressed the activity and induced ataxia during the first 20 min except at 14:00, but the activity depended on the lapse of time after the injection at all times. In circadian variations which developed higher susceptibility to the nicotine-induced ambulatory activity during successive 20 min segments of the test session, administration of a large dose of nicotine resulted in two peaks of response, one occurring at 18:00 and another at 6:00, in the periods between 0-20 and 60-80 min after injection, but the peak of susceptibility occurred at 22:00 in the periods between 80-100 and 100-120 min after injection. However, with the administration of a small dose of nicotine, there was no development of two peaks of susceptibility at any time.