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.
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Acknowledgments
The authors would like to thank Drs. Cindy Clayton and Rhonda Oates-O’Brien, Jessica Bond, and the husbandry staff for the research support.
Funding
This study received funding from the University of California, Davis, and NIH grant MH108319.
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All procedures described were approved by the UC-Davis Animal Care and Use Committee.
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Simmons, T.C., Singh, A.L.K. & Bales, K.L. Effects of systemic endocannabinoid manipulation on social and exploratory behavior in prairie voles (Microtus ochrogaster). Psychopharmacology 238, 293–304 (2021). https://doi.org/10.1007/s00213-020-05683-w
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DOI: https://doi.org/10.1007/s00213-020-05683-w