Baclofen blocks the development of sensitization to the locomotor stimulant effect of amphetamine
Baclofen blocks the development of sensitization to the locomotor stimulant effect of amphetamine
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DOI：
10.1097/01.fbp.0000179279.98029.e9
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发表时间：
2005-11-01
影响因子：
1.6
通讯作者：
Gaiardi, M
中科院分区：
文献类型：
--
作者：
Bartoletti, M;Gubellini, C;Gaiardi, M
GABA（B）激动剂巴氯芬（baclofen，BCF）可阻断苯丙胺（amphetamine，AMPH）运动效应的致敏作用，并在重复给药后逆转其致敏作用。本研究旨在探讨巴氯芬是否也能预防精神兴奋剂致敏的发展。当动物在重复处理结束后3天和30天被激发时，慢性AM PH处理（1.5 mg/kg i. p.，持续10天）导致对AM PH（1.5 mg/kg）的运动反应增加。长期共同给予BCF（2 mg/kg，i. p.）AMPH阻断了对AMPH兴奋作用的致敏作用的发展。辅助实验排除了“状态依赖”假设可以解释巴氯芬的作用。此外，先前单独用巴氯芬重复治疗对急性AMPH效应或随后对AMPH致敏的发展没有影响。总之，结果证实，GABA（B）受体在获得AMPH行为敏化中起重要作用，并进一步支持GABA（B）激动剂在治疗精神兴奋剂成瘾中的潜在用途。
The GABA(B) agonist baclofen (BCF) has recently been reported to block the expression of sensitization to the locomotor effect of amphetamine (AMPH), and to reverse it after repeated administration. The present study was undertaken to investigate whether baclofen could also prevent the development of sensitization to the psychostimulant. Chronic AM PH treatment (1.5 mg/kg i.p. for 10 days) led to an increased locomotor response to AM PH (1.5 mg/kg) when the animals were challenged 3 and 30 days after the end of repeated treatment. Chronic co-administration of BCF (2 mg/kg, i.p.) and AMPH blocked the development of sensitization to the stimulant effect of AMPH. An ancillary experiment excluded that a 'state-dependency' hypothesis could account for the effect of baclofen. Furthermore, a previous repeated treatment with baclofen alone had no influence either on the acute AMPH effect or on the subsequent development of sensitization to AMPH. In conclusion, the results confirm that GABA(B) receptors play an important role in the acquisition of AMPH behavioural sensitization and further support a potential use of GABA(B) agonists in the treatment of psychostimulant addiction.