Do Carmo Gail Pereira, Mello Nancy K, Rice Kenner C, Folk John E, Negus S Stevens
Alcohol and Drug Abuse Research Center, McLean Hospital - Harvard Medical School, Belmont, MA 02478, USA.
Eur J Pharmacol. 2006 Oct 10;547(1-3):92-100. doi: 10.1016/j.ejphar.2006.06.075. Epub 2006 Jul 5.
Delta agonists such as SNC80 ((+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) produce some cocaine-like behavioral effects and warrant evaluation as candidate "agonist" medications for cocaine abuse. The present study examined acute and chronic effects of the systemically active delta agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys. Acute SNC80 (0.32-3.2 mg/kg, i.m.) pretreatment dose-dependently decreased cocaine self-administration (0.0032 mg/kg/injection), but doses of SNC80 that decreased cocaine self-administration also decreased food-maintained responding. In chronic studies, SNC80 (0.32-3.2 mg/kg/h, i.v.) was delivered for 7 days, and food or cocaine (0.01 mg/kg/injection) was available during 4 daily components of food availability and 4 daily components of drug availability. Chronic SNC80 (1.8 mg/kg/h) tended to decrease cocaine self-administration but produced greater reductions in food-maintained responding. A higher dose of 3.2 mg/kg/h SNC80 eliminated both cocaine- and food-maintained responding and produced profound sedation in one monkey and was not tested in other monkeys. These findings indicate that SNC80 produced dose-dependent and non-selective reductions in cocaine self-administration. These results suggest that SNC80 is unlikely to be useful as a treatment for cocaine dependence.
δ 激动剂,如 SNC80((+)-4-[(aR)-α-((2S,5R)-4-烯丙基-2,5-二甲基-1-哌嗪基)-3-甲氧基苄基]-N,N-二乙基苯甲酰胺)会产生一些类似可卡因的行为效应,因此有必要作为可卡因滥用的候选“激动剂”药物进行评估。本研究考察了全身活性 δ 激动剂 SNC80 对恒河猴可卡因维持和食物维持反应的急性和慢性影响。急性给予 SNC80(0.32 - 3.2 毫克/千克,肌肉注射)预处理,剂量依赖性地降低了可卡因自我给药量(0.0032 毫克/千克/注射),但降低可卡因自我给药量的 SNC80 剂量也降低了食物维持反应。在慢性研究中,以 0.32 - 3.2 毫克/千克/小时的剂量静脉注射 SNC80,持续 7 天,在食物供应的 4 个每日时间段和药物供应的 4 个每日时间段内可获得食物或可卡因(0.01 毫克/千克/注射)。慢性给予 SNC80(1.8 毫克/千克/小时)倾向于降低可卡因自我给药量,但对食物维持反应的降低幅度更大。更高剂量的 3.2 毫克/千克/小时的 SNC80 消除了可卡因和食物维持反应,并在一只猴子中产生了深度镇静,未在其他猴子中进行测试。这些发现表明,SNC80 对可卡因自我给药产生了剂量依赖性和非选择性的降低作用。这些结果表明,SNC80 不太可能作为可卡因依赖的治疗药物。