Parametric investigation of social place preference in adolescent mice.

Abstract

Social interaction promotes survival by helping animals to form stable and supportive groups. Additionally, maladaptive social behavior is a hallmark of disorders such as autism and schizophrenia. In many different animal species, including humans, social interaction can be inherently rewarding. Lately there has been growing interest in studying the neurobiological underpinnings of social interaction and learned social behavior in rodent behavioral models. One common procedure is conditioned place preference (CPP) to measure the rewarding effects of social interaction and social reward learning. Social CPP was originally used in rats but has been adapted recently for use in mice, enabling use of the vast array of genetic tools available in mice.Here we studied the role of age, sex, bedding cues, and prior social isolation on the expression of social CPP in male and female mice. We found that without social deprivation male but not female mice display moderate but temporary social CPP during early adolescence but not adulthood. Early life social isolation increased social CPP in female but not male mice. In contrast, cocaine CPP was robust and long-lasting in male and female mice. Our results demonstrate that social CPP in mice is variable, occurring only under specific conditions, and that social isolation promotes social reward in female but not male mice. We discuss potential methodological and interpretive issues of the mouse social CPP model.

Establishment of a social conditioned place preference paradigm for the study of social reward in female mice

“…Moreover, it would be difficult to distinguish the lack of rewarding properties of the stimulus from reduced salience or a slower learning rate. Additionally, it could be hypothesized that the isolation context conditioning plays a much stronger role in juvenile mice, as was previously noted (Cann et al, 2020). Therefore, as a more plausible explanation, we found the effect of the length of conditioning reflects a difference in the underlying mechanism in adult vs. juvenile mice, although, admittedly this remains speculation without further evidence.…”

“…Cann and coauthors hypothesized that contact with unfamiliar individuals could be more rewarding for mice (Cann et al, 2020). This hypothesis was based on their own observation of unstable conditioning effects elicited by social contact with familiar mice (Cann et al, 2020) and more robust results acquired with a protocol using an unfamiliar individual as a stimulus animal (Bariselli et al, 2018). However, two other lines of observations suggest that social contact with familiar individuals should be more rewarding than with unfamiliar individuals.…”

“…Two opposing hypotheses concerning the effect of familiarity on social reward can be derived from the literature. Cann and coauthors hypothesized that contact with unfamiliar individuals could be more rewarding for mice (Cann et al, 2020). This hypothesis was based on their own observation of unstable conditioning effects elicited by social contact with familiar mice (Cann et al, 2020) and more robust results acquired with a protocol using an unfamiliar individual as a stimulus animal (Bariselli et al, 2018).…”

“…sCPP directly measures the reinforcing effect of social contact and is based on the same construct as the classic conditioned place preference test that is used extensively to test the rewarding effects of drugs. The sCPP protocol, with various modifications, has been instrumental in a series of studies showing the roles of serotonergic and oxytocin-dependent signaling in neuronal plasticity underlying social reward (Cann et al, 2020; Dölen et al, 2013; Hung et al, 2017; Nardou et al, 2019; Wei et al, 2015). Reported results show that rewarding effects of social contact could be robustly observed in juvenile animals; however, the effect of social interaction is diminished or absent in early adulthood at the age of 8 weeks in male mice and at 11 weeks in females (Nardou et al, 2019).…”

The neurochemistry of social reward during development: What have we learned from rodent models?

“…One of the most common experimental procedures used to study the neurobiological underpinnings of social reward in rodents is the conditioned place preference (CPP) paradigm, originally used in rats and subsequently adapted for use in mice (Cann et al 2020). This experimental approach, based on classical (Pavlovian) conditioning, allows to measure the rewarding properties of social interaction and social reward learning.…”