Cancela L M, Artinián J, Fulginiti S
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
Pharmacol Biochem Behav. 1988 Aug;30(4):899-904. doi: 10.1016/0091-3057(88)90117-7.
Rats were administered repeated IP injections of dl-amphetamine (AMPH) according to a chronic escalating dose schedule (three doses per 24 hr, for four days, two days or one day). Animals treated for four days exhibited a diminished oral stereotypy in response to a challenge of 12 mg/kg AMPH or 2 mg/kg SC apomorphine (APO), 72 hr after withdrawal. Pretreatment with 2 mg/kg IP naloxone (NAL) during the period of chronic AMPH administration prevented the reduction in oral stereotypy induced by AMPH or APO. No differences were detected among the mean of stereotypy scores from the different treatments in response to a challenge dose of 6 mg/kg AMPH. Neurochemical data showed that NAL pretreatment reversed the depletion of striatal dopamine content induced by chronic AMPH. When repeated injections of AMPH were given only one day, the diminished stereotypy response to AMPH or APO was not observed. Animals treated simultaneously with 1 mg/kg IP morphine or 5 micrograms/kg IP beta-endorphin and repeated AMPH injections for one day, showed a reduced stereotyped response to AMPH or APO. These results suggest that opioid peptides are involved in the mechanisms underlying the decrease in oral behaviors following AMPH treatment.
根据慢性递增剂量方案（每24小时注射三次，持续四天、两天或一天），给大鼠重复腹腔注射dl-苯丙胺（AMPH）。接受四天治疗的动物在撤药72小时后，对12mg/kg AMPH或2mg/kg皮下注射阿扑吗啡（APO）的激发反应中，口腔刻板行为减少。在慢性AMPH给药期间，用2mg/kg腹腔注射纳洛酮（NAL）预处理可防止AMPH或APO诱导的口腔刻板行为减少。在对6mg/kg AMPH激发剂量的反应中，不同治疗组的刻板行为评分平均值之间未检测到差异。神经化学数据表明，NAL预处理可逆转慢性AMPH诱导的纹状体多巴胺含量耗竭。当仅给予一天的重复AMPH注射时，未观察到对AMPH或APO的刻板行为反应减弱。同时用1mg/kg腹腔注射吗啡或5μg/kg腹腔注射β-内啡肽处理并重复AMPH注射一天的动物，对AMPH或APO的刻板行为反应降低。这些结果表明，阿片肽参与了AMPH治疗后口腔行为减少的潜在机制。
