Morales-Mulia Marcela, Panayi Fany, Lambás-Señas Laura, Scarna Hélène, Méndez Milagros
Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México D.F., Mexico.
Pharmacol Biochem Behav. 2007 Jun-Jul;87(2):232-40. doi: 10.1016/j.pbb.2007.04.019. Epub 2007 May 1.
Acute and repeated psychostimulant administration induces a long-lasting enhanced behavioural response to a subsequent drug challenge, known as behavioural sensitization. This phenomenon involves persistent neurophysiological adaptations, which may lead to drug addiction. Brain dopaminergic pathways have been implicated as the main neurobiological substrates of behavioural sensitization, although other neurotransmitters and neuromodulators may also participate. In order to investigate a possible involvement of opioid systems in amphetamine (AMPH) behavioural sensitization, we studied the AMPH-induced changes in Proenkephalin (Pro-Enk) mRNA expression in forebrain areas in both drug-naïve and AMPH-sensitized rats. Male Sprague-Dawley rats were sensitized to AMPH by means of a single AMPH (1 mg/kg s.c.) injection and the same dose was injected 7 days later to assess the expression of sensitization. Pro-Enk mRNA levels were evaluated by in situ hybridization in coronal brain sections. AMPH injection induced an increase in Pro-Enk mRNA expression in the nucleus accumbens and the medial-posterior caudate-putamen in drug-naïve rats. Challenge with AMPH to rats injected 1 week earlier with AMPH induced motor sensitization and increased and decreased Pro-Enk mRNA expression in the prefrontal cortex and the anterior medial caudate-putamen, respectively. Our results suggest that alterations in cortical and striatal enkephalinergic systems could contribute to the expression of AMPH behavioural sensitization.
急性和反复给予精神兴奋剂会诱导对随后药物激发产生持久增强的行为反应，即行为敏化。这种现象涉及持续的神经生理学适应，可能导致药物成瘾。脑多巴胺能通路被认为是行为敏化的主要神经生物学底物，尽管其他神经递质和神经调质也可能参与其中。为了研究阿片系统在苯丙胺（AMPH）行为敏化中可能的作用，我们研究了在未接触过药物和AMPH敏化的大鼠前脑区域中，AMPH诱导的脑啡肽原（Pro-Enk）mRNA表达的变化。雄性Sprague-Dawley大鼠通过单次皮下注射AMPH（1 mg/kg）使其对AMPH产生敏化，并在7天后注射相同剂量以评估敏化的表达。通过冠状脑切片原位杂交评估Pro-Enk mRNA水平。在未接触过药物的大鼠中，注射AMPH可诱导伏隔核和尾壳核中后部Pro-Enk mRNA表达增加。对1周前注射过AMPH的大鼠再次注射AMPH可诱导运动敏化，并分别使前额叶皮质和尾壳核前部内侧的Pro-Enk mRNA表达增加和减少。我们的结果表明，皮质和纹状体脑啡肽能系统的改变可能有助于AMPH行为敏化的表达。
