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 (5mg/kg, i.p.) did not affect basal locomotor or stereotypical activity. Methanandamide (5mg/kg, i.p.) pretreatment did not alter the acute increase in locomotor or stereotypical activities produced by acute amphetamine (2mg/kg, i.p.). For chronic studies, rats injected with amphetamine (2mg/kg, i.p.) once daily for 3 consecutive days were then challenged with amphetamine (2mg/kg, i.p.) 5 days later. Expression of locomotor sensitization was blocked when methanandamide (5mg/kg, i.p.) was given once, just prior to amphetamine (2mg/kg, i.p.) challenge. In rats co-exposed to methanandamide (5mg/kg, i.p.) and amphetamine (2mg/kg, i.p.) on days 1-3 and then challenged with amphetamine (2mg/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.
Rasmussen
Bruce A
BA
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140, USA.
Unterwald
Ellen M
EM
Kim
Jae K
JK
Rawls
Scott M
SM
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D007267:Injections; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001095:Arachidonic Acids; C088155:methanandamide; D000661:Amphetamine