Department of Pharmacology, Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Drug Alcohol Depend. 2012 Nov 1;126(1-2):257-62. doi: 10.1016/j.drugalcdep.2012.04.021. Epub 2012 May 29.
Abuse of a dangerous street drug called mephedrone (4-methylmethcathinone) has become commonplace in the United States. Mephedrone is hypothesized to possess abuse liability, share pharmacological properties with psychostimulants, and display toxicity that has been linked to fatalities and non-fatal overdoses. Knowledge about the pharmacology of mephedrone has been obtained primarily from surveys of drug abusers and emergency room visits rather than experimental studies. The present study used motor activity and conditioned place preference (CPP) assays to investigate behavioral effects of mephedrone. Acute mephedrone (3, 5, 10, 30 mg/kg, ip) administration increased ambulatory activity in rats. Mephedrone (5 mg/kg, ip)-induced ambulation was inhibited by pretreatment with a dopamine D1 receptor antagonist (SCH 23390) (0.5, 1, 2 mg/kg, ip) and enhanced by pretreatment with a dopamine D2 receptor antagonist (sulpiride) (2 mg/kg, ip). Rats injected for 5 days with low dose mephedrone (0.5 mg/kg, ip) and then challenged with mephedrone (0.5 mg/kg, ip) following 10 days of abstinence displayed sensitization of ambulatory activity. In CPP experiments, mephedrone (30 mg/kg, ip) conditioning elicited a preference shift in both rats and mice. The CPP and dopamine-sensitive motor activation produced by mephedrone is suggestive of abuse liability and indicates commonalities between the neuropharmacological profiles of mephedrone and established drugs of abuse.
在美国,滥用一种名为甲卡西酮的危险街头毒品已变得司空见惯。甲卡西酮据推测具有滥用倾向,与精神兴奋剂具有药理学特性,并显示出与死亡和非致命性过量有关的毒性。关于甲卡西酮的药理学知识主要是通过对吸毒者的调查和急诊室就诊获得的,而不是通过实验研究获得的。本研究使用运动活动和条件性位置偏好(CPP)测定来研究甲卡西酮的行为效应。急性甲卡西酮(3、5、10、30mg/kg,ip)给药增加了大鼠的活动性。多巴胺 D1 受体拮抗剂(SCH 23390)(0.5、1、2mg/kg,ip)预处理可抑制甲卡西酮(5mg/kg,ip)诱导的活动,而多巴胺 D2 受体拮抗剂(sulpiride)(2mg/kg,ip)预处理可增强其作用。连续 5 天给予低剂量甲卡西酮(0.5mg/kg,ip),然后在 10 天戒断后用甲卡西酮(0.5mg/kg,ip)进行挑战的大鼠显示出活动的敏化。在 CPP 实验中,甲卡西酮(30mg/kg,ip)条件作用引起了大鼠和小鼠的偏好转变。甲卡西酮引起的 CPP 和多巴胺敏感的运动激活表明其具有滥用倾向,并表明甲卡西酮与已确立的滥用药物的神经药理学特征之间存在共性。