PMID- 29595540 OWN - NLM STAT- MEDLINE DCOM- 20190801 LR - 20210223 IS - 1473-5849 (Electronic) IS - 0955-8810 (Linking) VI - 29 IP - 6 DP - 2018 Sep TI - Sex-specific differences in cannabinoid-induced extracellular-signal-regulated kinase phosphorylation in the cingulate cortex, prefrontal cortex, and nucleus accumbens of Lister Hooded rats. PG - 473-481 LID - 10.1097/FBP.0000000000000395 [doi] AB - Sex-dependent differences have been consistently described in cannabinoid addiction research. In particular, we recently reported that female Lister Hooded rats display greater self-administration of the cannabinoid CB1 receptor agonist WIN55,212-2 (WIN) and stronger reinstatement of cannabinoid-seeking behavior than males. Cannabinoids modulate the phosphorylation of the extracellular-signal-regulated kinase (ERK) pathway, leading to various forms of plasticity-related learning that likely affect operant behavior. However, whether or not the reported sex-dependent differences in cannabinoid-taking and cannabinoid-seeking behaviors may be related to a sexual dimorphic activation of the ERK pathway remains still to be determined. In the present study, we measured the level of phosphoERK-positive cells in the cingulate cortex (CG1), prefrontal cortex (PFCx), and nucleus accumbens of male and of intact (i.e. sham-operated) and ovariectomized female Lister Hooded rats 30 and 60 min after an acute, intravenous, injection of a dose of WIN (0.3 mg/kg) resembling the mean amount of drug daily self-administered by trained rats. We found that WIN significantly increased ERK activation in the CG1, PFCx, and nucleus accumbens in a sex time and, restricted to the cortical areas, layer-specific manner. Moreover, the comparison between intact and ovariectomized female rats revealed a significant role played by estrogens in WIN-elicited ERK activation. These results indicate, for the first time, the existence of a sexually dimorphic cannabinoid receptor-dependent ERK activation that, restricted to the CG1 and PFCx, is ovarian hormone-dependent. FAU - Rosas, Michela AU - Rosas M AD - Department of Life and Environmental Sciences, Pharmaceutical, Pharmacological and Nutraceutical Sciences Section. FAU - Porru, Simona AU - Porru S AD - Department of Life and Environmental Sciences, Pharmaceutical, Pharmacological and Nutraceutical Sciences Section. FAU - Giugliano, Valentina AU - Giugliano V AD - Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology. FAU - Antinori, Silvia AU - Antinori S AD - Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology. FAU - Scheggi, Simona AU - Scheggi S AD - Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. FAU - Fadda, Paola AU - Fadda P AD - Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology. AD - Department of Biomedical Sciences, Centre of Excellence 'Neurobiology of Addiction', University of Cagliari. FAU - Fratta, Walter AU - Fratta W AD - Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology. AD - Department of Biomedical Sciences, Centre of Excellence 'Neurobiology of Addiction', University of Cagliari. FAU - Acquas, Elio AU - Acquas E AD - Department of Life and Environmental Sciences, Pharmaceutical, Pharmacological and Nutraceutical Sciences Section. AD - Department of Biomedical Sciences, Centre of Excellence 'Neurobiology of Addiction', University of Cagliari. FAU - Fattore, Liana AU - Fattore L AD - Department of Biomedical Sciences, Centre of Excellence 'Neurobiology of Addiction', University of Cagliari. AD - CNR Institute of Neuroscience - Cagliari, National Research Council, Cagliari. LA - eng PT - Journal Article PL - England TA - Behav Pharmacol JT - Behavioural pharmacology JID - 9013016 RN - 0 (Analgesics) RN - 0 (Benzoxazines) RN - 0 (Cannabinoids) RN - 0 (Morpholines) RN - 0 (Naphthalenes) RN - 5H31GI9502 ((3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) MH - Analgesics/therapeutic use MH - Analysis of Variance MH - Animals MH - Benzoxazines/pharmacology MH - Brain/anatomy & histology/*drug effects/*enzymology MH - Cannabinoids/*pharmacology MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Female MH - Gyrus Cinguli/drug effects MH - Male MH - Morpholines/pharmacology MH - Naphthalenes/pharmacology MH - Nucleus Accumbens/drug effects MH - Ovariectomy MH - Phosphorylation/drug effects MH - Prefrontal Cortex/drug effects MH - Rats MH - *Sex Characteristics EDAT- 2018/03/30 06:00 MHDA- 2019/08/02 06:00 CRDT- 2018/03/30 06:00 PHST- 2018/03/30 06:00 [pubmed] PHST- 2019/08/02 06:00 [medline] PHST- 2018/03/30 06:00 [entrez] AID - 10.1097/FBP.0000000000000395 [doi] PST - ppublish SO - Behav Pharmacol. 2018 Sep;29(6):473-481. doi: 10.1097/FBP.0000000000000395.