Effects of systemic endocannabinoid manipulation on social and exploratory behavior in prairie voles ( Microtus ochrogas
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ORIGINAL INVESTIGATION
Effects of systemic endocannabinoid manipulation on social and exploratory behavior in prairie voles (Microtus ochrogaster) Trenton C. Simmons 1 & Alexis L. K. Singh 1 & Karen L. Bales 1 Received: 7 February 2020 / Accepted: 19 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Anandamide is an endocannabinoid that contributes to certain aspects of social behavior, like play and reward, by binding to cannabinoid receptor type 1 (CB1). Most interesting is the recent discovery that anandamide may be mobilized by oxytocin receptor activation under certain contexts, particularly in the nucleus accumbens. Objectives Given the established role of oxytocin and the nucleus accumbens in the neurobiology of pair-bonding, we investigated whether systemic administration of brain-permeable modulators of the endocannabinoid system could alter preferential partner contact in both male and female prairie voles. Methods Specifically, we tested whether intraperitoneal administration of the neutral CB1 antagonist AM4113 (4.0–16.0 mg/kg) or the anandamide hydrolysis inhibitor URB597 (5.0–20.0 mg/kg) could prevent or facilitate partner preference formation, respectively. To further investigate the specificity of effects on partner preference, we repeated our URB597 dosing regimen on an additional group of females and tested their anxiety-related behavior in both an elevated-plus maze and a light/dark test. Results AM4113 administration had no effect on partner preference. But while URB597 also had no effect on partner preference, low-dose females did increase absolute preferential contact with either the partner or the stranger; individual females spent significant contact time with either the partner or the stranger. None of our outcome measures in either anxiety test showed significant effects of treatment. Conclusions Our results reveal that experimentally increasing anandamide levels in female prairie voles can increase social contact with both a familiar and novel male via unknown mechanisms that are likely separate from anxiety reduction. Keywords Partner preference . Anxiety . Anandamide . Prairie vole . Pair-bond
Introduction Endocannabinoids are lipid metabolites that function within a relatively newly discovered physiological signaling system that is most widely studied for its role in mediating the effects of Cannabis sativa. The endocannabinoid system (ECS) includes an ever-growing list of endogenous neurotransmitters, receptors, and metabolic enzymes that operate within the same framework (Battista et al. 2012). Endocannabinoids are produced “on demand” from membrane phospholipid precursors and are rapidly degraded through local enzymatic activity, but not before acting as synaptic modulators (Battista et al. 2012). The signaling mechanism of endocannabinoids generally * Karen L. Bales [email protected] 1
Department of Psychology, University of California, Davis, Davis, CA, USA
involves retrograde neurotransmission and the subsequent inhibition of neur
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