Repeated alcohol: behavioral sensitization and alcohol-heightened aggression in mice

Rationale: Repeated administration of psychomotor stimulants or opiates can induce behavioral sensitization, typically detected as progressive and long-lasting increases in the motor-activating effects of these drugs. This phenomenon may be relevant to seizure susceptibility, drug self-administration, and sexual behavior. Repeated administration of alcohol can also induce behavioral sensitization and may have consequences on how alcohol affects aggressive behavior. Objectives: To (1) determine the enduring nature of locomotor sensitization to alcohol; (2) examine subsequent changes to morphine and amphetamine effects on locomotor behavior; and (3) test whether behavioral sensitization to alcohol or morphine is relevant to alcohol-heightened aggression. Methods and results: In the first experiment, male CFW mice were given ten injections of alcohol (2.4 g/kg/day), morphine (30.0 mg/kg/day), or saline. Video tracking confirmed locomotor sensitization - an approximate 200% increase in the motor-stimulating effects of these drugs. Challenges with 2.0 g/kg alcohol revealed that locomotor sensitization to alcohol persisted for at least 2 months. Alcohol-sensitized mice showed evidence of cross-tolerance to the sedative effects of morphine (5 mg/kg) but showed no evidence of cross-sensitization to the stimulant effects of 30.0 mg/kg morphine or 1.0 mg/kg amphetamine. In the second experiment, under conditions resulting in species-typical aggressive behavior against a male intruder, there were no differences in the aggressive behavior relative to saline control mice following alcohol or morphine sensitization. However, in the mice sensitized to alcohol, but not to morphine, there was a vertical shift in the dose-effect curve for moderate doses of alcohol (0.6-1.7 g/kg, p.o.). In addition, twice as many alcohol-sensitized mice consistently showed alcohol-heightened aggression when compared with the saline control mice (74% vs 37%, respectively). Conclusions: Repeated administration of alcohol can sensitize locomotor stimulation and may also render mice more vulnerable to increased aggression after alcohol. Moreover, the results suggest that at least some of the neuroadaptations caused by repeated administration of alcohol are relevant to alcohol-heightened aggression.