Methanandamide blocks amphetamine-induced behavioral sensitization in rats

Methanandamide acts at targets which modulate amphetamine-induced behaviors. Therefore, we investigated methanandamide effects on the acute hyperactivity produced by a single injection of amphetamine and behavioral sensitization induced by repeated amphetamine exposure in rats. Methanandamide (5 mg/kg, i.p.) did not affect basal locomotor or stereotypical activity. Methanandamide (5 mg/kg, i.p.) pretreatment did not alter the acute increase in locomotor or stereotypical activities produced by acute amphetamine (2 mg/kg, i.p.). For chronic studies, rats injected with amphetamine (2 mg/kg, i.p.) once daily for 3 consecutive days were then challenged with amphetamine (2 mg/kg, i.p.) 5 days later. Expression of locomotor sensitization was blocked when methanandamide (5 mg/kg, i.p.) was given once, just prior to amphetamine (2 mg/kg, i.p.) challenge. In rats co-exposed to methanandamide (5 mg/kg, i.p.) and amphetamine (2 mg/kg, i.p.) on days 1–3 and then challenged with amphetamine (2 mg/kg, i.p.) following 5 days of drug absence, the development of both locomotor and stereotypical sensitization was blocked. The ability of methanandamide to block amphetamine-sensitized behaviors suggests that this pharmacologically diverse lipid regulates signaling events impacted by repeated psychostimulant exposure.