Repeated administration of methamphetamine causes sensorimotor gating deficits in experimental animals and human. However, the withdrawal effects after the repeated administration of methamphetamine have been still unclear. In this study, we investigated the involvement of cannabinoid CB₁ receptors on impairment of sensorimotor gating function during withdrawal in mice repeatedly administered with methamphetamine.
Mice were subcutaneously administered methamphetamine (1.8 mg/kg), every other day for 30 days. After methamphetamine withdrawal, the mice were tested a sensorimotor gating function by the prepulse inhibition test. AM251 (3.2 mg/kg, s.c.), a CB₁ receptor antagonist, was administrated in mice repeatedly administered with methamphetamine.
Prepulse inhibition was significantly suppressed during withdrawal after repeated methamphetamine. This impairment of prepulse inhibition was ameliorated by AM251 in combination with repeated methamphetamine and also by AM251 during withdrawal after repeated methamphetamine. However, singly administration of AM251 before the test could not altered the prepulse inhibition deficits.
These findings suggest that persistent activation of the CB₁ receptors could lead to the development of sensorimotor gating deficits during withdrawal after repeated methamphetamine administration.