Consequence of Two Protocols of Social Defeat Stress on Nicotine-Induced Psychomotor Effects in Mice

Abstract

Exposure to stress may contribute to enhanced vulnerability to drug use disorders, by altering sensitivity to drug-related reward and psychomotor effects. This study aimed to characterize the psychomotor effects of nicotine administration and then investigate the consequences of two types of repeated social defeat stress (episodic and continuous) on nicotine-induced psychomotor effects in mice. Adult male Swiss mice were treated for 13 days with daily injections of nicotine (0.1, 0.4, or 1.0 mg/kg, s.c.) and received saline and nicotine challenges (0, 0.1 and 0.4 mg/kg) after a withdrawal period. Dose-dependent effects were observed in locomotor response to nicotine, with trends for locomotor stimulation after intermittent (but not acute) administration of 0.1 mg/kg. Higher nicotine doses caused acute locomotor suppression (0.4 and 1.0 mg/kg) and tolerance after intermittent administration (0.4 mg/kg dose). In separate cohorts, experimental mice were daily defeated by aggressive mice, using the resident-intruder model, for 10 days. After brief confrontations, intruders returned to their home cage (episodic stress) or were continuously exposed to the aggressive resident for 24 h (continuous stress), until the following defeat. After the 10-day stress protocol, mice received saline and nicotine challenges (0 and 0.1 mg/kg, s.c.) in locomotor tests. Mice were also tested for methamphetamine-induced locomotor response (1.0 mg/kg, i.p.). Both defeat protocols induced short-term locomotor suppression (24h after stress), which was further suppressed by nicotine only in mice exposed to continuous defeat stress. Ten days after stress, locomotor behavior was no longer suppressed in defeated mice of either stress protocol. Mice exposed to continuous defeat stress showed a reduced stimulant response to methamphetamine, 12 days after termination of stress. Our findings indicate that exposure to continuous defeat stress facilitates nicotine-induced locomotor suppression shortly after stress and reduces methamphetamine-induced stimulation in the long term.