Different effects of valproate on methamphetamine- and cocaine-induced behavioral sensitization in mice

Repetitive exposure to psychostimulants elicits behavioral sensitization. Accumulating evidence have shown that the central GABAergic system is involved in psychostimulants sensitization. Valproate, a clinically widely used anticonvulsant mood-stabilizing agent, can modulate central GABAergic neurotransmission. Herein, the effects of valproate on the development and expression of behavioral sensitization to methamphetamine (METH) and cocaine was studied in mice. Behavioral sensitization of METH and cocaine was rendered by injection of METH (2.0 mg/kg) or cocaine (20 mg/kg) once daily for seven days. Locomotor activity was measured by an ambulometer. Single or multiple administration of valproate (37.5, 75, 150 mg/kg) could not decrease acute METH- and cocaine-induced hyperactivity. Co-administration of valproate with METH or cocaine dose-dependently inhibited the development of behavioral sensitization. Single administration of valproate (37.5, 75, 150 mg/kg) did not affect the expression of behavioral sensitization induced by METH and cocaine. Multiple administration of valproate (37.5, 75, 150 mg/kg) dose-dependently inhibited the expression of behavioral sensitization to METH, but not to cocaine. The present results supported that METH- and cocaine-induced behavioral sensitization possesses distinct neural mechanisms, which implies that valproate may have different modulatory effect on METH and cocaine addiction in humans.