Sex-dependent differences in the effects of cannabinoids on the emotional brain
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1
CNR, National Research Council, Institute of Neuroscience-Cagliari c/o Dept Biomedical Sciences, Univ. Cagliari, Italy
Sex dependent differences have been frequently observed in the biological and behavioural effects of substances of abuse, including cannabis. We recently demonstrated that self-administration of the CB1 receptor (CB1R) agonist WIN 55,212-2 in female Lister Hooded rats is more rapidly acquired, more robustly maintained, and more slowly extinguished than in their male counterparts. A follow-up study revealed that drug- and cue-induced reinstatement of drug-seeking after extinction is stronger in female than in male rats, with ovariectomy typically dampening responding, thus confirming the pivotal role of sex and oestrous cycle in modulating cannabinoid-taking and seeking behaviours. Intriguingly, we found that cannabinoid self-administration significantly alters levels and functionality of CB1Rs in reward-related brain areas of male rats. In this study, we investigated the influences of sex in the regulation of CB1R density and function, measured by quantitative autoradiographic binding studies with [3H]CP55940 and CP55940-stimulated [35S]GTPγS binding autoradiography, respectively, in selected brain areas of male and intact female rats. Moreover, since estrogen has been recently found to affect limbic cannabinoid receptor binding, we also evaluated CB1R density and functionality in brain regions involved in emotional and cognitive functions, i.e. prefrontal cortex (Cg1 and Cg3), caudate-putamen, nucleus accumbens (core and shell), amygdala (Amy) and hippocampus, in ovariectomised female rats (OVX), and in OVX rats pre-treated with estradiol (OVX-E). Our results revealed that in the Amy, cycling females showed a significant decreased CB1R density when compared to males. This group also showed lower CB1R binding site density in Cg1 and Cg3, although the differences did not reach statistical significance. Conversely, OVX group showed higher CB1R density than cycling females in the Cg1, Cg3, and Amy, a difference that appears to be estradiol-dependent since it is no more evident in the OVX-E group. Moreover, within the Amy, in parallel with the decrease in CB1R density, CP55940-stimulated [35S]GTPγS binding was significantly lower in OVX-E female rats relative to both males and cycling females, while no difference was observed either in CB1R densities or function in any of the other brain areas analyzed. Finally, sex and estradiol were found to also affect motor activity, sensorimotor gating and sociability in rats tested in the open field, in the pre-pulse inhibition and social interaction tasks, respectively. In conclusion, by demonstrating that both sex and estradiol affect CB1R density and activity in certain limbic regions, our findings provide a putative biochemical mechanism underlying the reported sex differences in cannabinoid-induced behavioural effects.
Keywords:
Cannabinoids,
sex differences,
emotion,
drug addiction,
Ovariectomy,
Estrogens
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Fattore
L
(2013). Sex-dependent differences in the effects of cannabinoids on the emotional brain.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00032
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Received:
28 Jan 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Dr. Liana Fattore, CNR, National Research Council, Institute of Neuroscience-Cagliari c/o Dept Biomedical Sciences, Univ. Cagliari, Monserrato-Cagliari, Sardinia, 09042, Italy, liana.fattore@in.cnr.it