Michela Rosas1, Simona Porru1, Sandro Fenu2,3, Stefania Ruiu4, Alessandra T Peana5, Alessandro Papale6, Riccardo Brambilla6, Gaetano Di Chiara2,3, Elio Acquas7,8. 1. Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale, 72, I-09124, Cagliari, Italy. 2. Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. 3. Centre of Excellence on Neurobiology of Addiction, University of Cagliari, Cagliari, Italy. 4. Institute of Translational Pharmacology, National Research Council, Pula, Cagliari, Italy. 5. Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy. 6. Neuroscience and Mental Health Research Institute (NMHRI), Neuroscience Division - School of Biosciences, Cardiff University, Cardiff, UK. 7. Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale, 72, I-09124, Cagliari, Italy. acquas@unica.it. 8. Centre of Excellence on Neurobiology of Addiction, University of Cagliari, Cagliari, Italy. acquas@unica.it.
Abstract
RATIONALE: 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. OBJECTIVES: 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. METHODS: The pERK1/2 expression was assessed by immunohistochemistry. RESULTS: 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. CONCLUSIONS: 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.
RATIONALE: 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. OBJECTIVES: 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-1mice. METHODS: The pERK1/2 expression was assessed by immunohistochemistry. RESULTS: 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-1mice; 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. CONCLUSIONS: 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.
Authors: Alessandro Zocchi; Elena Girlanda; Giorgia Varnier; Ilaria Sartori; Lara Zanetti; Grant A Wildish; Mark Lennon; Manolo Mugnaini; Christian A Heidbreder Journal: Synapse Date: 2003-12-15 Impact factor: 2.562
Authors: Jason P Schroeder; Marina Spanos; Jennie R Stevenson; Joyce Besheer; Michael Salling; Clyde W Hodge Journal: Neuropharmacology Date: 2008-07-04 Impact factor: 5.250