Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats

Kohli, Shivali and King, Madeleine V. and Williams, Stuart and Edwards, Adele and Ballard, Theresa M. and Steward, Lucinda J. and Alberati, Daniella and Fone, Kevin C.F. (2018) Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats. Neuropsychopharmacology . ISSN 1740-634X

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Abstract

The pituitary neuropeptide oxytocin promotes social behavior, and is a potential adjunct therapy for social deficits in schizophrenia and autism. Oxytocin may mediate pro-social effects by modulating monoamine release in limbic and cortical areas, which was investigated herein using in vivo microdialysis, after establishing a dose that did not produce accompanying sedative or thermoregulatory effects that could concomitantly influence behavior. The effects of oxytocin (0.03-0.3mg/kg s.c.) on locomotor activity, core body temperature and social behavior (social interaction and ultrasonic vocalisations) were examined in adult male Lister-hooded rats, using selective antagonists to determine the role of oxytocin and vasopressin V1A receptors. Dopamine and serotonin (5-HT) efflux in the prefrontal cortex (PFC) and nucleus accumbens (NAc) of conscious rats were assessed using microdialysis. 0.3mg/kg oxytocin modestly reduced activity and caused hypothermia but only the latter was attenuated by the V1A receptor antagonist, SR49059 (1mg/kg i.p.). Oxytocin at 0.1mg/kg, which did not alter activity or temperature, significantly attenuated PCP-induced hyperactivity and increased social interaction between unfamiliar rats without altering the number or pattern of ultrasonic vocalisations. In the same rats, oxytocin (0.1 mg/kg) selectively elevated dopamine overflow in the NAc (F(1, 12)=7.983, P=0.0153), but not PFC, without influencing 5-HT efflux. Systemic oxytocin administration attenuated PCP-induced hyperactivity and increased pro-social behavior without decreasing core body temperature and selectively enhanced NAc dopamine release, consistent with activation of mesocorticolimbic circuits regulating associative/reward behavior being involved. This highlights the therapeutic potential of oxytocin to treat social behavioral deficits seen in psychiatric disorders such as schizophrenia and autism.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: https://doi.org/10.1038/s41386-018-0171-0
Depositing User: Fone, Kevin
Date Deposited: 21 Aug 2018 10:58
Last Modified: 07 Feb 2019 04:30
URI: http://eprints.nottingham.ac.uk/id/eprint/53168

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