From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long‐term adverse consequences of drug use?

Abstract

Addictive drugs can profoundly affect social behaviour both acutely and in the long-term. Effects range from the artificial sociability imbued by various intoxicating agents to the depressed and socially withdrawn state frequently observed in chronic drug users. Understanding such effects is of great potential significance in addiction neurobiology. In this review we focus on the 'social neuropeptide' oxytocin and its possible role in acute and long-term effects of commonly used drugs. Oxytocin regulates social affiliation and social recognition in many species and modulates anxiety, mood and aggression. Recent evidence suggests that popular party drugs such as MDMA and gamma-hydroxybutyrate (GHB) may preferentially activate brain oxytocin systems to produce their characteristic prosocial and prosexual effects. Oxytocin interacts with the mesolimbic dopamine system to facilitate sexual and social behaviour, and this oxytocin-dopamine interaction may also influence the acquisition and expression of drug-seeking behaviour. An increasing body of evidence from animal models suggests that even brief exposure to drugs such as MDMA, cannabinoids, methamphetamine and phencyclidine can cause long lasting deficits in social behaviour. We discuss preliminary evidence that these adverse effects may reflect long-term neuroadaptations in brain oxytocin systems. Laboratory studies and preliminary clinical studies also indicate that raising brain oxytocin levels may ameliorate acute drug withdrawal symptoms. It is concluded that oxytocin may play an important, yet largely unexplored, role in drug addiction. Greater understanding of this role may ultimately lead to novel therapeutics for addiction that can improve mood and facilitate the recovery of persons with drug use disorders.

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

“…There is emerging evidence supporting the involvement of OT in the effects of a number of drugs of abuse (Broadbear et al , 2011, McGregor and Bowen, 2012, McGregor et al , 2008, Sarnyai, 2011. With respect to MAP, an inhibitory effect of OT has been demonstrated on MAP-induced hyperlocomotion and conditioned place preference (CPP) (Qi et al , 2008, Qi et al , 2009) and on dopamine release in the Acb (Qi et al, 2008) demonstrating a key role for OT in the modulation of behavioural effects of MAP, possibly via a dopaminergicdependent mechanism.…”

Genetic Deletion of Trace Amine 1 Receptors Reveals Their Role in Auto-Inhibiting the Actions of Ecstasy (MDMA)

“…The monoamine releaser and reuptake suppressor, "ecstasy" [3,4-methylenedioxymetamphetamine (MDMA)], facilitates prosocial behaviors in animals and humans (Bedi et al, 2009;Johansen and Krebs, 2009), actions related to enhanced release of oxytocin in centers controlling social behavior, like amygdala and septum (McGregor et al, 2008). However, greater attention has been devoted to the psychostimulant properties of MDMA and its widespread recreational use (Vollenweider et al, 1999(Vollenweider et al, , 2002.…”

Oxytocin-induced elevation of ADP-ribosyl cyclase activity, cyclic ADP-riboseor Ca2+ concentrations is involved in autoregulation of oxytocin secretionin the hypothalamus and posterior pituitary in male mice

“…This short polypeptide hormone is secreted dendritically from neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus and spread to other areas of the brain (McGregor et al, 2008;Skuse and Gallgher, 2009). Locally released OT in the brain causes excitation of OT neurons by activating OT receptors, a class A family (2.1:OXY:1:OT: in IUPHA data base; http://www.iuphar-db.org/GPCR/ReceptorListForward?class=class%20A), expressed on both neurons of the PVN and SON and nerve endings in the posterior pituitary (Adan et al, 1995;Freund-Mercier et al, 1994;Young et al, 1997).…”