Elsevier

Neuroscience

Volume 197, 1 December 2011, Pages 269-279
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression

https://doi.org/10.1016/j.neuroscience.2011.09.008Get rights and content

Abstract

Components of the brain's dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35–P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc), and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence.

Highlights

▶The effects of adolescent stress on drug preferences in adulthood were studied. ▶Adolescent social defeat increases adult amphetamine conditioned place preference. ▶Adolescent foot-shock does not alter amphetamine conditioned place preference. ▶Accumbens core D2 dopamine receptors are reduced by amphetamine place training. ▶Adolescent social defeat abolishes amphetamine-induced D2 receptor reductions.

Section snippets

Animals

Male Sprague–Dawley rats (Animal Resource Center, University South Dakota, Vermillion, SD, USA) used as experimental animals were pair-housed under a reverse light cycle (lights off from 10:00–22:00 h) on postnatal day (P) 21. Resident adult male Sprague–Dawley rats (300–400 g) for social defeat experiments were housed singly prior to aggressive screening. Food and water was available ad libitum. The experimental procedures were approved by the Institutional Animal Care and Use Committee of the

Locomotion and conditioned place preference

When locomotion over time was analyzed during the first acclimation exposure to the CPP apparatus in adulthood for rats that had experienced adolescent social defeat, a significant effect of stress pretreatment (F(1,58)=18.741; P=0.014) and time (F(5,272)=22.721; P<0.001) was observed. Post hoc tests showed that socially defeated rats exhibited a significantly greater degree of locomotion in the novel CPP apparatus during the 5–10 min time period (P=0.007) and the final 25–30 min time period (P

Discussion

This study is the first to investigate the effects of social defeat in adolescence on adult conditioned place preference. Most notably, these data suggest that adolescent social defeat stress, but not mild foot-shock stress, increases preference for amphetamine-paired cues in adulthood. In addition, we observed increased locomotion in the novel CPP apparatus following adolescent social defeat stress. Individual locomotion in the novel environment was correlated with the degree of amphetamine

Acknowledgments

This work was supported by NIDA RO1 DA019921 (G.L.F.), Sigma XiG200803150251 (A.R.B.), a USD Graduate Research Award (A.R.B.), and NIH P20 RR015567 which is designated a Center of Biomedical Research Excellence (COBRE). We thank Dr. Jodi L. Lukkes for her valuable technical assistance with these experiments.

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      Much of that work in adults has strongly implicated CRF as a key mediator of the relation between social defeat and increased drug intake. Like adults, adolescents exposed to social defeat and subsequently tested in adulthood show increased CPP to amphetamine, cocaine, and alcohol (Burke et al., 2011; Montagud-Romero et al., 2017; Rodríguez-Arias et al., 2017; Whitaker et al., 2013), as well as increased SA of cocaine and alcohol (Burke and Miczek, 2015; Rodriguez-Arias et al., 2016). Despite this evidence, there is relatively little known about the specific role of CRF in mediating the effect of adolescent social defeat on drug abuse vulnerability in adulthood.

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