Strain and sex differences in the locomotor response and behavioral sensitization to cocaine in hyperactive rats

Individual variability in the behavioral responsiveness to psychostimulant drugs is due, in part, to genetic factors. The present study investigated the effects of acute and repeated administrations of cocaine (0, 5, 10 or 20 mg/kg, i.p.) on locomotor activity in male and female rats from genetically distinct strains often used as a model of human childhood hyperactivity/attentional deficit disorder: Wistar Kyoto Hyperactive (WKHA) rats, Spontaneous Hypertensive rats (SHR) and their control Wistar Kyoto (WKY). The results, expressed as percent change in locomotor activity relative to respective control groups, showed that cocaine elicits a dose-dependent hyperactivity in all strains and revealed neither strain nor sex differences in acute sensitivity to moderate doses of the drug. Nevertheless, across repeated administrations, strain and sex differences appeared: WKHA rats displayed a moderate extent of sensitization to psychomotor stimulant effects of cocaine and female rats showed more robust sensitization than males, whatever the strain. These findings support the genotype-dependence in the development of behavioral sensitization to cocaine and confirm the robustness of the sexual dimorphism across different inbred rat strains. Interestingly, the present results demonstrate that sensitization to psychostimulant drugs occurs in genetically hyperactive strains as well as in their normoactive control strain.