Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA.
Psychopharmacology (Berl). 2013 May;227(1):117-26. doi: 10.1007/s00213-012-2945-0. Epub 2012 Dec 20.
Rats bred for high (HiS) and low (LoS) saccharin intake exhibit divergent behavioral responses to multiple drugs of abuse, with HiS rats displaying greater vulnerability to drug taking. Previous research indicates that this effect may be due to increased sensitivity to reward in HiS rats and to the aversive effects of acute drug administration in LoS rats.
The current study investigated whether HiS and LoS rats also exhibit different behavioral signs of withdrawal following one or repeated opiate exposures.
Emotional signs of opiate withdrawal were assessed with potentiation of the acoustic startle reflex and conditioned place aversion (CPA) in male and female HiS and LoS rats. Startle was measured before and 4 h after a 10-mg/kg injection of morphine on days 1, 2, and 7 of opiate exposure. CPA was induced with a 2-day, naloxone-precipitated conditioning paradigm. Somatic signs of withdrawal and weight loss were also measured.
Male and female LoS rats exhibited lower startle potentiation than HiS rats on the seventh day of morphine exposure. LoS male rats also failed to develop a CPA to morphine withdrawal. No differences in physical withdrawal signs were observed between HiS and LoS rats, but males of both lines had more physical signs of withdrawal than females.
These results suggest that LoS rats are less vulnerable to the negative emotional effects of morphine withdrawal than HiS rats. A less severe withdrawal syndrome may contribute to decreased levels of drug taking in the LoS line.
高(HiS)和低(LoS)糖精摄入量的大鼠表现出对多种滥用药物的不同行为反应,HiS 大鼠对药物的易感性更高。先前的研究表明,这种效应可能是由于 HiS 大鼠对奖励的敏感性增加以及 LoS 大鼠急性药物给药的厌恶效应所致。
本研究调查了 HiS 和 LoS 大鼠在单次或重复阿片类药物暴露后是否也表现出不同的戒断行为迹象。
雄性和雌性 HiS 和 LoS 大鼠的听觉惊吓反射增强和条件位置厌恶(CPA)评估阿片类药物戒断的情绪迹象。在阿片类药物暴露的第 1、2 和 7 天,在 10mg/kg 吗啡注射后 4 小时测量惊吓。CPA 通过为期两天的纳洛酮诱发的条件形成范式诱导。还测量了躯体戒断迹象和体重减轻。
在吗啡暴露的第 7 天,雄性和雌性 LoS 大鼠的惊吓增强低于 HiS 大鼠。LoS 雄性大鼠也未能对吗啡戒断产生 CPA。HiS 和 LoS 大鼠之间未观察到躯体戒断迹象的差异,但两种系的雄性比雌性有更多的躯体戒断迹象。
这些结果表明,LoS 大鼠对吗啡戒断的负面情绪影响的易感性低于 HiS 大鼠。较轻的戒断综合征可能导致 LoS 系的药物摄入水平降低。