Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
Addict Biol. 2011 Jan;16(1):20-9. doi: 10.1111/j.1369-1600.2009.00199.x.
Amphetamine, and other stimulants, readily induces behavioral sensitization, an effect hypothesized to reflect neurobiological changes that may underlie certain aspects of drug addiction. Apart from the effects on the dopamine system, previous studies have also shown that amphetamine interacts with other neurotransmitters, including the endogenous opioid system. The unselective opioid receptor antagonist naltrexone (NTX) modulates amphetamine-induced effects in both laboratory animals and humans. To further examine this interaction, the aim of the present study was to investigate the effect of NTX on the expression of locomotor sensitization and conditioned locomotor response in animals previously conditioned with amphetamine. Sensitization was induced by repeated administration of amphetamine (2 mg/kg) for 10 consecutive days. After a 10-day drug-free period, the rats were administered NTX (3 mg/kg) 30 minutes prior to the administration of a challenge dose of either amphetamine (0.5 mg/kg) (test for drug-induced sensitization) or saline (test for conditioned locomotor response). NTX had no effect on acute amphetamine-induced locomotor activity or on general locomotor activity in animals without a history of amphetamine conditioning. However, animals previously conditioned with amphetamine showed a sensitized locomotor response to the amphetamine challenge following the 10-day drug-free period. This sensitized response was significantly inhibited by NTX pre-treatment. In addition, NTX pre-treatment blocked the conditioned locomotor response when the amphetamine-conditioned animals were placed in the previously amphetamine-paired context. This study showed that NTX attenuates drug- and cue-induced locomotor behavior in amphetamine-conditioned animals, supporting recent clinical findings that indicated a potential role of NTX as a treatment for amphetamine dependence.
安非他命和其他兴奋剂很容易引起行为敏感化，这种效应被假设反映了神经生物学的变化，这些变化可能是某些药物成瘾方面的基础。除了对多巴胺系统的影响外，先前的研究还表明，安非他命与其他神经递质相互作用，包括内源性阿片系统。非选择性阿片受体拮抗剂纳曲酮（NTX）调节实验室动物和人类中安非他命引起的作用。为了进一步研究这种相互作用，本研究旨在研究 NTX 对先前用安非他命条件的动物的运动敏感化和条件运动反应表达的影响。通过连续 10 天给予安非他命（2mg/kg）来诱导敏感化。在 10 天无药物期后，在给予挑战剂量安非他命（0.5mg/kg）（测试药物诱导的敏感化）或生理盐水（测试条件运动反应）之前，30 分钟给予 NTX（3mg/kg）。NTX 对急性安非他命诱导的运动活动或无安非他命条件的动物的一般运动活动没有影响。然而，以前用安非他命条件的动物在 10 天无药物期后对安非他命挑战表现出敏感的运动反应。这种敏感反应明显被 NTX 预处理抑制。此外，当安非他命条件的动物被放置在以前与安非他命配对的环境中时，NTX 预处理阻断了条件运动反应。这项研究表明，NTX 可减弱安非他命条件动物的药物和线索诱导的运动行为，支持最近的临床发现，表明 NTX 作为安非他命依赖治疗的潜在作用。
