Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140, USA.
Eur J Pharmacol. 2010 Feb 10;627(1-3):150-5. doi: 10.1016/j.ejphar.2009.10.059. Epub 2009 Oct 30.
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.
甲酰胺作用于调节安非他命诱导行为的靶点。因此，我们研究了甲酰胺对单次安非他命注射引起的急性过度活动和重复安非他命暴露引起的行为敏感化的影响。甲酰胺（5mg/kg，ip）不影响基础运动或刻板活动。甲酰胺（5mg/kg，ip）预处理不改变急性安非他命（2mg/kg，ip）引起的运动或刻板活动的急性增加。对于慢性研究，每天一次腹腔注射安非他命（2mg/kg）连续 3 天的大鼠，然后在 5 天后用安非他命（2mg/kg，ip）挑战。当甲酰胺（5mg/kg，ip）在安非他命（2mg/kg，ip）挑战前仅给予一次时，运动敏化的表达被阻断。在第 1-3 天同时暴露于甲酰胺（5mg/kg，ip）和安非他命（2mg/kg，ip）的大鼠，然后在 5 天的药物停药后用安非他命（2mg/kg，ip）挑战，运动和刻板敏感化的发展都被阻断。甲酰胺阻断安非他命敏化行为的能力表明，这种药理学上多样化的脂质调节了反复精神兴奋剂暴露所影响的信号事件。
