Maurice T, Romieu P
Laboratory of Cerebral Plasticity, CNRS FRE 2693, University of Montpellier II, cc 090, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
Pharmacopsychiatry. 2004 Nov;37 Suppl 3:S198-207. doi: 10.1055/s-2004-832678.
Cocaine induces in the brain a drastic plasticity affecting numerous neurotransmission systems. In turn, the drug provokes a complex pattern of behavioral responses, including locomotor hyperactivity, stereotyped behaviors, sensitization, and appetitive and reinforcing properties that rapidly generate the addictive process. The involvement of sigma (1) receptors in cocaine effects has been suggested initially through the observation that sigma (1) antagonists could attenuate several acute effects induced by the drug, such as hyperlocomotion, stereotypies, convulsions and lethality. We will describe thereafter the recent results showing that activation of the sigma (1) receptor is also involved in the appetitive properties of cocaine, as measured using place preference conditioning in mice. Using selective sigma (1) antagonists or an in vivo antisense strategy, the role of the sigma (1) receptor in acquisition, expression and reactivation of conditioned place preference was demonstrated. The observation that repeated administration of cocaine rapidly provokes overexpression of the sigma (1) receptor outlines its major role in these first psychological steps of addictive processes. The physiological interaction between cocaine and sigma (1) receptors is detailed and the possibility that effective therapeutical strategies could target the sigma (1) receptor is considered.
可卡因会在大脑中引发剧烈的可塑性变化，影响众多神经传递系统。反过来，这种药物会引发一系列复杂的行为反应模式，包括运动亢进、刻板行为、敏感化以及具有快速引发成瘾过程的奖赏和强化特性。最初通过观察到σ（1）受体拮抗剂可减弱该药物诱导的几种急性效应，如运动亢进、刻板行为、惊厥和致死性，提示了σ（1）受体与可卡因效应有关。此后，我们将描述最近的研究结果，这些结果表明，如通过在小鼠中使用位置偏爱条件反射所测量的，σ（1）受体的激活也与可卡因的奖赏特性有关。使用选择性σ（1）受体拮抗剂或体内反义策略，证实了σ（1）受体在条件性位置偏爱的获得、表达和再激活中的作用。反复给予可卡因会迅速引发σ（1）受体的过表达，这一观察结果突显了其在成瘾过程这些最初心理步骤中的主要作用。详细阐述了可卡因与σ（1）受体之间的生理相互作用，并探讨了有效的治疗策略以σ（1）受体为靶点的可能性。
