Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale, 72, 09124, Cagliari, Italy.
Neurobiology Section and Center for Neural Circuits and Behavior, Division of Biological Sciences, University of California, San Diego, USA.
Psychopharmacology (Berl). 2018 Jan;235(1):59-69. doi: 10.1007/s00213-017-4740-4. Epub 2017 Oct 3.
Extracellular signal-regulated kinase (ERK) phosphorylation is critical for neuronal and behavioural functions; in particular, phosphorylated ERK (pERK) expression in the nucleus accumbens (Acb) of the rat is stimulated by addictive drugs with the exception of morphine, which decreases accumbal ERK phosphorylation in the Sprague-Dawley and Wistar rats. The psychogenetically selected Roman low- (RLA) and high-avoidance (RHA) rats differ behaviourally and neurochemically in many responses to addictive drugs. In particular, morphine elicits a greater increment in locomotor activity and in dopamine transmission in the Acb of RHA vs RLA rats. However, the effects of morphine on place conditioning (conditioned place preference (CPP)) and ERK phosphorylation in the Roman lines remain unknown.
To characterize in the Roman lines the reinforcing properties of morphine (i.e. morphine-elicited CPP acquisition) and the relationship between these properties and its effects on ERK phosphorylation in the Acb, the behavioural effects of morphine were evaluated in a place-conditioning apparatus and ERK phosphorylation was assessed by immunohistochemistry in the shell and core subregions of the Acb of rats both acutely administered with morphine or undergoing conditioning.
Morphine elicited CPP in both Roman lines and decreased pERK expression in the Acb of RLA but not RHA rats. Such decrease was prevented by conditioning.
These findings indicate that the selective breeding of the Roman lines has generated a divergence, in terms of morphine-elicited pERK expression but not of morphine-elicited CPP, between RLA and RHA rats and sustain the observation that changes in pERK expression in the Acb are not a requisite for the reinforcing effects of morphine.
细胞外信号调节激酶(ERK)磷酸化对于神经元和行为功能至关重要;特别是,除了吗啡之外,成瘾药物会刺激大鼠伏隔核(Acb)中磷酸化 ERK(pERK)的表达,而吗啡会降低 Sprague-Dawley 和 Wistar 大鼠的伏隔核 ERK 磷酸化。从心理上选择的罗曼低(RLA)和高回避(RHA)大鼠在许多对成瘾药物的反应中表现出行为和神经化学上的差异。特别是,吗啡会在 RHA 大鼠的 Acb 中引起更大的运动活动和多巴胺传递增加,而不是 RLA 大鼠。然而,吗啡对位置条件作用(条件性位置偏好(CPP))和罗曼线中 ERK 磷酸化的影响仍然未知。
为了在罗曼线中描述吗啡的强化特性(即吗啡引起的 CPP 获得)及其与吗啡对 Acb 中 ERK 磷酸化的影响之间的关系,通过在位置条件作用装置中评估吗啡的行为效应,并通过免疫组织化学评估吗啡急性给药或进行条件作用后大鼠 Acb 的壳核和核区中 ERK 磷酸化,来评估吗啡对吗啡的行为效应。
吗啡在罗曼线中均引起 CPP,并降低了 RLA 但不是 RHA 大鼠 Acb 中的 pERK 表达。这种减少可以通过条件作用来预防。
这些发现表明,罗曼线的选择性繁殖导致了 RLA 和 RHA 大鼠在吗啡引起的 pERK 表达方面而非吗啡引起的 CPP 方面的差异,并支持了这样的观察结果,即 Acb 中 pERK 表达的变化不是吗啡强化作用的必要条件。