Deiana Serena, Fattore Liana, Spano M Sabrina, Cossu Gregorio, Porcu Emanuele, Fadda Paola, Fratta Walter
Department of Neuroscience, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato (Cagliari), Sardinia, Italy.
Neuropharmacology. 2007 Feb;52(2):646-54. doi: 10.1016/j.neuropharm.2006.09.007. Epub 2006 Nov 13.
Cannabinoids have been reported to sustain self-administration in laboratory animals; however, genetic differences and environmental factors critical in the initiation and retention of such behaviour are yet to be defined. This study investigated the acquisition, maintenance and extinction of self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 (6.25-25 microg/kg/inf) in Long Evans, Lister Hooded and Sprague-Dawley rats under a continuous schedule of reinforcement and two different response-like operanda, nose-poking and lever-pressing. Results showed that Long Evans and Lister Hooded, but not Sprague Dawley, rats acquired and retained stable cannabinoid self-administration behaviour under both modus operandi, as defined by significant differences between responding in the active versus the inactive hole/lever. In rats developing firm self-administration, substitution of saline for WIN 55,212-2 extinguished the responding, supporting the notion that cannabinoids may serve as a positive reinforcer in laboratory animals. Nevertheless, significant differences among strains and responding modalities were observed in the percentage of acquisition, amount of drug intake during maintenance and timing of extinction. In addition, no significant strain differences were found in motor response to WIN 55,212-2 (0.3 and 3.0 mg/kg), thus excluding that strain differences observed during cannabinoid self-administration could be related to different cannabinoid-induced locomotor effects.
据报道，大麻素能维持实验动物的自我给药行为；然而，在这种行为的起始和维持过程中起关键作用的基因差异和环境因素尚未明确。本研究在持续强化程序以及两种不同的类似反应操作方式（鼻触和杠杆按压）下，研究了大麻素CB1受体激动剂WIN 55,212-2（6.25-25微克/千克/注射）在长 Evans 大鼠、利斯特戴帽大鼠和斯普拉格-道利大鼠中的自我给药行为的习得、维持和消退情况。结果表明，长 Evans 大鼠和利斯特戴帽大鼠，而非斯普拉格-道利大鼠，在两种操作方式下都习得并维持了稳定的大麻素自我给药行为，这由主动孔/杠杆与非主动孔/杠杆的反应差异显著来定义。在形成稳固自我给药行为的大鼠中，用生理盐水替代WIN 55,212-2可使反应消退，这支持了大麻素可能作为实验动物的阳性强化物的观点。然而，在习得百分比、维持期间的药物摄入量以及消退时间方面，品系和反应方式之间存在显著差异。此外，在对WIN 55,212-2（0.3和3.0毫克/千克）的运动反应中未发现显著的品系差异，因此排除了在大麻素自我给药过程中观察到的品系差异可能与不同的大麻素诱导的运动效应有关的可能性。
