Itzhak Y, Martin J L
Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, FL 33136, USA.
Psychopharmacology (Berl). 2000 Aug;151(2-3):226-33. doi: 10.1007/s002130000394.
Recent studies have suggested the involvement of excitatory amino acid (EAA) and inhibitory gamma amino butyric acid (GABA) transmission in the effects of psychostimulants such as cocaine and amphetamines.
The present study was undertaken to investigate whether drugs that are considered to inhibit glutamate release (e.g., riluzole) or increase GABAergic transmission (e.g., gabapentin) attenuate the induction and expression of sensitization to cocaine and methamphetamine (METH) in Swiss Webster mice.
Sensitization to the psychomotor stimulating effect of cocaine and METH was rendered by five daily injections of cocaine (20 mg/kg) or METH (1.0 mg/kg). Locomotor activity was measured by infrared beam interrupts.
Pretreatment with riluzole (2.5-20.0 mg/kg) affected neither the expression nor the induction of sensitization to cocaine. The pretreatment with riluzole (20 mg/kg) blocked the acute response to METH on day 1 and the expression of the sensitized response on day 5 but not the induction of sensitization to METH. Pretreatment with gabapentin (10 mg/kg and 30 mg/kg) affected neither the expression nor the induction of sensitization to cocaine. The pretreatment with gabapentin attenuated the acute response to METH on day 1 and the expression of the sensitized response on day 5, but it failed to block the induction of sensitization to METH. Psychostimulant-induced conditioned locomotion was affected neither by riluzole nor by gabapentin.
Riluzole and gabapentin had no effect on the induction of sensitization to cocaine and METH; however, they attenuated the expression of sensitization to METH but not to cocaine. These findings suggest that riluzole- and gabapentin-mediated changes in EAA and GABAergic transmission, respectively, had no effect on mechanisms associated with the induction of sensitization, but they may affect the expression of the sensitized response to METH.
近期研究表明，兴奋性氨基酸（EAA）和抑制性γ-氨基丁酸（GABA）传递参与了可卡因和苯丙胺等精神兴奋剂的作用。
本研究旨在探讨被认为可抑制谷氨酸释放的药物（如利鲁唑）或增强GABA能传递的药物（如加巴喷丁）是否能减弱瑞士韦伯斯特小鼠对可卡因和甲基苯丙胺（METH）的敏化诱导和表达。
通过每日注射五次可卡因（20毫克/千克）或METH（1.0毫克/千克）使小鼠对可卡因和METH的精神运动刺激作用产生敏化。通过红外光束中断来测量运动活性。
利鲁唑（2.5 - 20.0毫克/千克）预处理对可卡因敏化的表达和诱导均无影响。利鲁唑（20毫克/千克）预处理在第1天阻断了对METH的急性反应以及第5天敏化反应的表达，但未阻断对METH的敏化诱导。加巴喷丁（10毫克/千克和30毫克/千克）预处理对可卡因敏化的表达和诱导均无影响。加巴喷丁预处理减弱了第1天对METH的急性反应以及第5天敏化反应的表达，但未能阻断对METH的敏化诱导。精神兴奋剂诱导的条件性运动既不受利鲁唑影响，也不受加巴喷丁影响。
利鲁唑和加巴喷丁对可卡因和METH敏化的诱导均无影响；然而，它们减弱了对METH而非可卡因的敏化表达。这些发现表明，利鲁唑和加巴喷丁分别介导的EAA和GABA能传递变化对与敏化诱导相关的机制无影响，但可能影响对METH敏化反应的表达。
