The Hormonal Regulation of Dorsal Hippocampal D2-Type Dopamine Receptor Mediated Social Learning in Male and Female Mice

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University of Guelph

Abstract

The regulatory mechanisms of social learning, or learning by watching or observing others, are poorly understood, but in animals may be tested using the social transmission of food preference (STFP). The STFP has implicated the dorsal hippocampus (DH), estrogens, androgens, and dopamine (DA) in the regulation of social learning. Previously, we found that DH D2-type DA receptor antagonism blocked social learning in gonadectomized (GDX) but not gonadally intact male and female mice, suggesting an interplay between DH D2-type DA receptors and gonadal hormones in the regulation of social learning. The specific hormones at play remain unknown. Here, we GDX male and female mice and replaced hormones to determine whether any could protect against the impairing effects of DH D2-type DA receptor antagonism on social learning. In males, gonadal testosterone may exert its effects directly at androgen receptors or indirectly at estrogen receptors following aromatization. In chapter 2, castrated (CAS) male observer “OBS” mice received either long-term estradiol benzoate (EB) or vehicle (VEH) silastic capsules (study 1), or dihydrotestosterone, a potent androgen, or VEH capsules (study 2). In chapter 3, ovariectomized (OVX) female OBS received long-term EB or VEH capsules. In chapter 4, CAS (study 1) and OVX (study 2) OBS received long-term progesterone (P4) or VEH pellets. In chapters 2-4, after 10 days of continuous hormone replacement, GDX OBS received bilateral infusions of the D2-type DA receptor antagonist raclopride (20 µg/µL for male;18 µg/µL for females) into the DH 10-minutes prior to a 30-minute social interaction with a recently fed, same-sex, familiar “demonstrator” (DEM). In chapter 5, P4 receptor knockout (PRKO) and wildtype (WT) adult female OBS underwent a 15-minute social interaction with a recently fed, same-sex, familiar DEM. All chapters ended with an 8-hour OBS choice test between two novel flavored diets. When social learning occurs, OBS prefer the DEM diet. Long-term hormone replacement protected against the impairing effects of DH D2-type DA receptor antagonism on social learning in chapter 2-4, and PRKO impaired social learning in chapter 5. Findings from this thesis elucidate the hormonal regulation of the social brain via interactions with the DA system.

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Keywords

Social Learning, Dopamine, Sex Hormones, Dorsal Hippocampus, D2-type Dopamine Receptors

Citation

Paletta, P., Aspesi, D., Bass, N., & Choleris, E. (2023). The Study of Social Cognition: Social Recognition and Social Learning in Laboratory Rats and Mice. In Animal Models of Reproductive Behavior (pp. 1-31). New York, NY: Springer US. https://doi.org/10.1007/978-1-0716-3234-5_1