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Cited by 171Neuroendocrine regulation and behaviorNeurotransmitter Receptor Influence on BehaviorNeuropeptides and Animal Physiology

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

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McGregor, I S, Callaghan, P D, Hunt, G E·2008·British Journal of Pharmacology
DOI 10.1038/bjp.2008.132PMC PMC2442436
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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 Effects range from the artificial sociability imbued by various intoxicating agents to the depressed and socially withdrawn state frequently observed in chronic drug users.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. British Journal of Pharmacology (2008) 154, 358–368; doi:fn1

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  1. In a key study, withdrawal symptoms arising from sudden precipitated cannabinoid abstinence in rats and were reversed by administration of lithium, via an OT-dependent mechanism (Cui et al., 2001). Lithium produces pronounced activation of OT-positive hypothalamic nuclei and the ability of lithium to prevent abstinence effects was reversed by co-administration of the OT antagonist L-368,899. Moreover, L-368,899 given in the absence of lithium, exacerbated the cannabinoid withdrawal syndrome. In an analogous fashion, symptoms arising from naloxone-precipitated withdrawal from morphine in mice were attenuated by co-administration of lithium via an OT-dependent mechanism (You et al., 2001). These findings have prompted preliminary trials of lithium in treating cannabis withdrawal with encouraging results (Bowen et al., 2005; Winstock et al., in press) and such trials could conceivably be extended to future examination of intranasal OT or other OT-releasing compounds as therapeutics.
  2. While MDMA exerts an acute prosocial effect on rats (Figure 2a), we and others have repeatedly noted that rats given even brief exposure to small doses of MDMA show subsequent deficits in social interaction, effects that can be detected many weeks and months after drug exposure (Figure 2d, Table 2). Thus the short-term ‘ultrasocial' state produced by MDMA appears to be followed by a much longer lasting ‘antisocial' state. The behavioural changes occurring as a result of MDMA pre-exposure are not only social in nature: pre-exposed rats show prolonged increases in anxiety on the elevated plus maze and emergence tests, have poorer memory than controls and are impaired in their coping responses to acute stress in the forced swim test (Morley et al., 2001; McGregor et al., 2003b; Thompson et al., 2004). These effects are mirrored in some recent studies of human MDMA users, where anxiety and depressive disorders may be over-represented and impairment in processing of social cues is evident (Parrott and Marsden, 2006; Reay et al., 2006).
  3. Van Nieuwenhuijzen PS, Bayes PM, Hunt GE, McGregor IS. Lasting social deficits in rats following repeated exposure to Gamma-hydroxybutyrate (GHB) and 3,4-Methylenedioxymethamphetamine (MDMA) Society for Neuroscience Abstracts: 2007;810:819. [Google Scholar]
  4. Winstock AR, Lea T, Copeland J. Lithium carbonate in the management of cannabis withdrawal. J Psychopharmacology. in press. [DOI] [PubMed]

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Authors
McGregor, I. S., Callaghan, P. D., & Hunt, G. E.
Affiliations
The University of Sydney (AU)
Corresponding author
McGregor, I S
ORCID
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2008-05
Volume
154
Issue
2
Pages
358-368
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
DOI
10.1038/bjp.2008.132
PMC
PMC2442436
OpenAlex
W1480251240
Cited by
171
References
123
Citations by year
2026: 3 · 2025: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 7 · 2017: 16 · 2016: 15 · 2015: 15 · 2014: 14 · 2013: 16 · 2012: 13
FWCI
2.26
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 273 d)
Locations
  • British Journal of Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion)
Funders
  • National Health and Medical Research Council
  • National Medical Research Council
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
oxytocin, drug addiction, social behavior, MDMA, gamma-hydroxybutyric acid, mesolimbic dopamine system, drug-seeking behavior, social dysfunction, neural adaptation, drug withdrawal, cannabinoids, methamphetamine, phencyclidine, social affiliation, anxiety, aggression
MeSH terms
Adaptation, Physiological, Adaptation, Psychological, Central Nervous System Stimulants, Animals, Brain, Dopamine, Humans, Limbic System, Neuropeptides, Oxytocin, Reinforcement, Psychology, Social Behavior, Substance Withdrawal Syndrome, Time Factors, Behavior, Addictive, N-Methyl-3,4-methylenedioxyamphetamine, Substance-Related Disorders, Amphetamine-Related Disorders

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