Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2009 Nov-Dec;61(6):1042-9. doi: 10.1016/s1734-1140(09)70166-5.
The present study was designed to find out whether pharmacological activation of GABA(B) receptors played a role in cocaine sensitization. To this end, male Wistar rats were injected with baclofen or 3-aminopropyl(methyl)phosphinic acid (SKF 97541), the potent and selective GABA(B) receptor agonists. The rats, which were repeatedly (for 5 days) administered with cocaine (10 mg/kg) and then challenged with cocaine (10 mg/kg) after 5-day withdrawal period, showed significantly higher locomotor hyperactivity in comparison with the effect observed in saline-pretreated and cocaine challenged rats. Baclofen (1.25, 2.5 and 5 mg/kg), administered for 5 days prior to cocaine, dose-dependently attenuated cocaine sensitization. When injected in the same treatment regimen, SKF 97541 (0.03 mg/kg) reduced the development of cocaine sensitization. To examine the effects of baclofen and SKF 97541 on the expression of cocaine sensitization, the drugs were given acutely before a challenge dose of cocaine (10 mg/kg) on day 10. Either baclofen (2.5 and 5 mg/kg) or SKF 97541 (0.1 mg/kg) decreased sensitization to cocaine. Our findings implicate a role of GABA(B) receptors in locomotor responses to cocaine. More specifically, they show that stimulation of GABA(B) receptors exerted inhibitory actions on acute locomotor responses to cocaine and on the expression of cocaine sensitization, what may offer a therapeutic potential of GABA(B) receptor agonists in the treatment of cocaine dependence.
本研究旨在探讨 GABA(B) 受体的药理学激活是否在可卡因敏化中发挥作用。为此，雄性 Wistar 大鼠被注射巴氯芬或 3-氨基丙基（甲基）膦酸（SKF 97541），这两种都是强效和选择性 GABA(B) 受体激动剂。与生理盐水预处理和可卡因挑战的大鼠相比，反复（5 天）给予可卡因（10mg/kg），然后在 5 天戒断期后再给予可卡因（10mg/kg）的大鼠表现出明显更高的运动过度活跃。巴氯芬（1.25、2.5 和 5mg/kg），在可卡因前 5 天给药，剂量依赖性地减弱了可卡因敏化。当以相同的治疗方案给药时，SKF 97541（0.03mg/kg）降低了可卡因敏化的发展。为了研究巴氯芬和 SKF 97541 对可卡因敏化表达的影响，在第 10 天给予可卡因挑战剂量（10mg/kg）之前，急性给予这些药物。巴氯芬（2.5 和 5mg/kg）或 SKF 97541（0.1mg/kg）均可降低可卡因的敏化。我们的发现表明 GABA(B) 受体在可卡因引起的运动反应中发挥作用。更具体地说，它们表明 GABA(B) 受体的刺激对急性可卡因运动反应和可卡因敏化的表达具有抑制作用，这可能为 GABA(B) 受体激动剂在可卡因依赖治疗中的治疗潜力提供了依据。
