Sex-specific differences in cannabinoid-induced extracellular-signal-regulated kinase phosphorylation in the cingulate cortex, prefrontal cortex, and nucleus accumbens of Lister Hooded rats. Issue 6 (September 2018)

• Record Type: Journal Article
• Authors: Rosas, Michela; Porru, Simona; Giugliano, Valentina; Antinori, Silvia; Scheggi, Simona; Fadda, Paola; Fratta, Walter; Acquas, Elio; Fattore, Liana
• Is Part Of: Behavioural pharmacology. Volume 29:Issue 6(2018)
• Publication Date: 2018-09
• Subjects: cannabinoids -- cingulate cortex -- extracellular-signal-regulated kinase -- nucleus accumbens -- prefrontal cortex -- rat -- sex differences -- WIN55, 212-2; Psychopharmacology -- Periodicals; Nervous System -- drug effects -- Periodicals; Behavior -- drug effects -- Periodicals; 615.78
• DOI: 10.1097/FBP.0000000000000395
• Languages: English
• ISSNs: 0955-8810

Abstract

Abstract : 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.