Social Bonding Decreases the Rewarding Properties of Amphetamine through a Dopamine D1 Receptor-Mediated Mechanism

Abstract

Although the protective effects of social bonds on drug use/abuse have been well documented, we know little about the underlying neural mechanisms. Using the prairie vole (Microtus ochrogaster)—a socially monogamous rodent that forms long-term pair bonds after mating—we demonstrate that amphetamine (AMPH) conditioning induced a conditioned place preference (CPP) in sexually naïve (SN), but not pair-bonded (PB), males. Although AMPH treatment induced a similar magnitude of DA release in the nucleus accumbens (NAcc) of SN and PB males, it had differential effects on NAcc D1 receptor (D1R) binding. Specifically, AMPH treatment increased D1R binding in SN, but decreased D1R binding in PB males. NAcc D1R, but not D2R, antagonism blocked AMPH-induced CPP in SN males and NAcc D1R activation prior to AMPH conditioning enabled AMPH-induced CPP in PB males. Together, our data demonstrate that pair bonding experience decreases the rewarding properties of AMPH through a D1R mediated mechanism.

Pair bonding prevents reinforcing effects of testosterone in male California mice in an unfamiliar environment

“…dopamine system) associated with pair bond formation have been uncovered [11,12], less is known about how the pair-bonding experiences affect the reinforcing properties of hormones or neurochemicals. Formation of a pair bond in male prairie voles (Microtus ochrogaster) decreases the effect of the drug amphetamine on the formation of a CPP [13]. This finding suggests that social experience can alter the reinforcing effects of other external and internal stimuli.…”

Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A2A receptor-independent mechanism

“…Accumulating evidence showing a strong interaction between neuronal markers of social behaviour and those of stress and mood regulation (Dabrowska et al , 2011, Debiec, 2005, Di Simplicio et al , 2009, Heinrichs and Gaab, 2007, Windle et al , 2004) and of drug reward/withdrawal (Liu et al , 2011, suggest that the "social" neuropeptide oxytocin (OT) and its receptor (OTR) may be implicated in the modulation of at least some of these methamphetamine-induced effects. OT is primarily synthesized by the magnocellular neurons of the supraoptic (SON) and paraventricular (PVN) 5 nuclei of the hypothalamus projecting to the posterior pituitary gland where it is stored in vesicles and it is released into the bloodstream to exert its peripheral effects (Fig.…”

The Effects of Oxytocin on Withdrawal, Craving and Stress Response in Heroin-Dependent Patients: A Randomized, Double-Blind Clinical Trial

“…Recent studies indicate that social attachments protect against addiction and health consequences of stress, whereas drug abuse and chronic stress can undermine social attachment [29,30]. Indeed, negative social experiences generally increase the vulnerability to drug abuse, while the development of strong social attachments, including parent-offspring and adult pair bonding may buffer substance abuse [31].…”