Rosas Michela, Porru Simona, Fenu Sandro, Ruiu Stefania, Peana Alessandra T, Papale Alessandro, Brambilla Riccardo, Di Chiara Gaetano, Acquas Elio
Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale, 72, I-09124, Cagliari, Italy.
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Psychopharmacology (Berl). 2016 Aug;233(15-16):2943-54. doi: 10.1007/s00213-016-4340-8. Epub 2016 May 31.
Despite the critical role attributed to phosphorylated extracellular signal regulated kinase (pERK1/2) in the nucleus accumbens (Acb) in the actions of addictive drugs, the effects of morphine on ERK1/2 phosphorylation in this area are still controversial.
In order to investigate further this issue, we studied (1) the ability of morphine to affect ERK1/2 phosphorylation in the shell (AcbSh) and core (AcbC) of Sprague-Dawley and Wistar rats and of CD-1 and C57BL/6J mice and (2) the role of dopamine D1 and μ-opioid receptors in Sprague-Dawley rats and CD-1 mice.
The pERK1/2 expression was assessed by immunohistochemistry.
In rats, morphine decreased AcbSh and AcbC pERK1/2 expression, whereas in mice, increased it preferentially in the AcbSh compared with the AcbC. Systemic SCH 39166 decreased pERK1/2 expression on its own in the AcbSh and AcbC of Sprague-Dawley rats and CD-1 mice; furthermore, in rats, SCH 39166 disclosed the ability of morphine to stimulate pERK1/2 expression. Systemic (rats and mice) and intra-Acb (rats) naltrexone prevented both decreases, in rats, and increases, in mice.
These findings confirm the differential effects of morphine in rats and mice Acb and that D1 receptors exert a facilitatory role on ERK1/2 phosphorylation; furthermore, they indicate that, in rats, removal of the D1-dependent pERK1/2 expression discloses the stimulatory influence of morphine on ERK1/2 phosphorylation and that the morphine's ability to decrease pERK1/2 expression is mediated by Acb μ-opioid receptors. Future experiments may disentangle the psychopharmacological significance of the effects of morphine on pERK1/2 in the Acb.
尽管磷酸化细胞外信号调节激酶（pERK1/2）在伏隔核（Acb）中对成瘾性药物作用起着关键作用，但吗啡对该区域ERK1/2磷酸化的影响仍存在争议。
为了进一步研究这个问题，我们研究了（1）吗啡影响Sprague-Dawley和Wistar大鼠以及CD-1和C57BL/6J小鼠伏隔核壳部（AcbSh）和核心部（AcbC）中ERK1/2磷酸化的能力，以及（2）多巴胺D1和μ-阿片受体在Sprague-Dawley大鼠和CD-1小鼠中的作用。
通过免疫组织化学评估pERK1/2的表达。
在大鼠中，吗啡降低了AcbSh和AcbC中pERK1/2的表达，而在小鼠中，与AcbC相比，吗啡优先增加了AcbSh中pERK1/2的表达。全身性给予SCH 39166自身可降低Sprague-Dawley大鼠和CD-1小鼠AcbSh和AcbC中pERK1/2的表达；此外，在大鼠中，SCH 39166揭示了吗啡刺激pERK1/2表达的能力。全身性（大鼠和小鼠）以及伏隔核内（大鼠）给予纳曲酮可防止大鼠中pERK1/2表达的降低以及小鼠中pERK1/2表达的增加。
这些发现证实了吗啡对大鼠和小鼠Acb的不同影响，并且D1受体对ERK1/2磷酸化发挥促进作用；此外，它们表明，在大鼠中，去除依赖D1的pERK1/2表达揭示了吗啡对ERK1/2磷酸化的刺激作用，并且吗啡降低pERK1/2表达的能力是由Acbμ-阿片受体介导的。未来的实验可能会阐明吗啡对Acb中pERK1/2作用的心理药理学意义。
