Long-Term Behavioral Effects of Post-weaning Social Isolation in Males and Females

Abstract

Adolescence is a developmental period associated with vast neural and behavioral changes which are accompanied by altered sensitivity to stimuli, both stressful and rewarding. Perturbations, especially stressful stimuli, during this period have been shown to alter behavior in adulthood. Social isolation rearing is one such perturbation. This review highlights the long-term behavioral consequences of adolescent social isolation rearing in rodents with a specific focus on anxiety- and addiction-related behaviors. Sex-specific effects are discussed where data are available. We then consider changes in monoaminergic neurotransmission as one possible mechanism for the behavioral effects described. This research on both normative and perturbed adolescent development is crucial to understanding and treating the increased vulnerability to psychiatric disorders seen in humans during this life stage.

Keywords: addiction; adolescence; anxiety; depression; dopamine; isolation rearing; reward; serotonin.

Figure 1

A summary of how adolescent isolation rearing alters behavioral outcomes in male and female rodents. (A) A schematic of developmental markers from birth to adulthood in male (solid lines) and female (dashed lines) rodents. Social interactions/behaviors are indicated at each development milestone and correspond to changes in gonadal hormones and changes within the dopamine (DA) system. (B) Effects of isolation rearing on anxiety-related behaviors. In males, stress early in adolescence has opposite effects on anxiety-related behaviors than late adolescent isolation. (C) Effects of isolation rearing on addiction-related behaviors. While little information is available regarding how adolescent isolation rearing affects females, it increases addiction-related behaviors in males.

Figure 2

A schematic of the behavioral tests utilized to assess the effects of social isolation rearing on anxiety- (top) and addiction- (bottom) related behaviors. (A,B) Anxiety-related behavioral tests include elevated plus maze (A) and open field (B). An animal is considered less anxious if they spend more time in the open arm of an elevated plus maze and the center of an open field. (C,D) Addiction-related behavioral tests include conditioned place preference (CPP; C) and self-administration (SA; D). An animal who forms a preference for the side of a chamber where they received a drug in CPP is considered to find that drug more rewarding (C). In SA paradigms (D), animals learn that pressing the active lever but not the inactive lever results in an injection of a drug of abuse. Animals are thought to find drugs of abuse more rewarding if they learn the operant task more quickly.

Figure 3

A summary of how adolescent social isolation rearing alters serotonin (top) and DA (bottom) dynamics within the reward circuitry of rodents. Social isolation rearing has been shown to alter metabolism (red) and release (orange and yellow) of serotonin in the PFC, NAc and HIP in a region-specific manner. Similarly, social isolation rearing has been shown to alter baseline DA (pink) as well as metabolism (red), release (orange and yellow) and reuptake through actions on DAT (green) in a region-specific manner. Abbreviations: PFC, prefrontal cortex; NAc, nucleus accumbens; BLA, basolateral amygdala; HIP, hippocampus; NE, no effect; DAT, dopamine transporter.