Male and Female Rats Differ in Brain Cannabinoid CB1 Receptor Density and Function and in Behavioural Traits Predisposing to Drug Addiction: Effect of Ovarian Hormones

Author(s): Maria Paola Castelli, Paola Fadda, Angelo Casu, Maria Sabrina Spano, Alberto Casti, Walter Fratta, Liana Fattore

Journal Name: Current Pharmaceutical Design

Volume 20 , Issue 13 , 2014

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Sex-dependent differences are frequently observed in the biological and behavioural effects of substances of abuse, including cannabis. We recently demonstrated a modulating effect of sex and oestrous cycle on cannabinoid-taking and seeking behaviours. Here, we investigated the influence of sex and oestrogen in the regulation of cannabinoid CB1 receptor density and function, measured by [3H]CP55940 and CP55940-stimulated [35S]GTPγS binding autoradiography, respectively, in the prefrontal cortex (Cg1 and Cg3), caudate- putamen, nucleus accumbens, amygdala and hippocampus of male and cycling female rats, as well as ovariectomised (OVX) rats and OVX rats primed with oestradiol (10 µg/rat) (OVX+E). CB1 receptor density was significantly lower in the prefrontal cortex and amygdala of cycling females than in males and in OVX females, a difference that appeared to be oestradiol-dependent, because it was no more evident in the OVX+E group. CP55940-stimulated [35S]GTPγS binding was significantly higher in the Cg3 of OVX rats relative to cycling and OVX+E rats. No difference was observed in CB1 receptor density or function in any of the other brain areas analysed. Finally, sex and oestradiol were also found to affect motor activity, social behaviour and sensorimotor gating in rats tested in locomotor activity boxes, social interaction and prepulse inhibition tasks, respectively. Our findings provide biochemical evidence for sex- and hormone- dependent differences in the density and function of CB1 receptors in selected brain regions, and in behaviours associated with greater vulnerability to drug addiction, revealing a more vulnerable behavioural phenotype in female than in male rats.

Keywords: Sex difference, ovariectomy, oestrogen, CB1 receptor and [35S]GTPγS binding, locomotor activity, social interaction, anxiety, prepulse inhibition.

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Article Details

Year: 2014
Published on: 07 May, 2014
Page: [2100 - 2113]
Pages: 14
DOI: 10.2174/13816128113199990430
Price: $65

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