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

Kohli, Shivali; King, Madeleine V.; Williams, Stuart; Edwards, Adele; Ballard, Theresa M.; Steward, Lucinda J.; Alberati, Daniella; Fone, Kevin C. F.

Authors

Shivali Kohli

Stuart Williams

Adele Edwards

Theresa M. Ballard

Lucinda J. Steward

Daniella Alberati

Kevin C. F. Fone



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 (0.03–0.3 mg/kg subcutaneous) on locomotor activity, core body temperature, and social behavior (social interaction and ultrasonic vocalizations) were examined in adult male Lister-hooded rats, using selective antagonists to determine the role of oxytocin and vasopressin V1a receptors. Dopamine and serotonin efflux in the prefrontal cortex and nucleus accumbens of conscious rats were assessed using microdialysis. 0.3 mg/kg oxytocin modestly reduced activity and caused hypothermia but only the latter was attenuated by the V1a receptor antagonist, SR49059 (1 mg/kg intraperitoneal). Oxytocin at 0.1 mg/kg, which did not alter activity and had little effect on temperature, significantly attenuated phencyclidine-induced hyperactivity and increased social interaction between unfamiliar rats without altering the number or pattern of ultrasonic vocalizations. In the same rats, oxytocin (0.1 mg/kg) selectively elevated dopamine overflow in the nucleus accumbens, but not prefrontal cortex, without influencing serotonin efflux. Systemic oxytocin administration attenuated phencyclidine-induced hyperactivity and increased pro-social behavior without decreasing core body temperature and selectively enhanced nucleus accumbens 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.

Citation

Kohli, S., King, M. V., Williams, S., Edwards, A., Ballard, T. M., Steward, L. J., …Fone, K. C. F. (2019). Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats. Neuropsychopharmacology, 44(2), 295-305. https://doi.org/10.1038/s41386-018-0171-0

Journal Article Type Article
Acceptance Date Jul 26, 2018
Online Publication Date Aug 7, 2018
Publication Date Jan 1, 2019
Deposit Date Sep 25, 2018
Publicly Available Date Mar 28, 2024
Journal Neuropsychopharmacology
Print ISSN 0893-133X
Electronic ISSN 1740-634X
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 44
Issue 2
Pages 295-305
DOI https://doi.org/10.1038/s41386-018-0171-0
Public URL https://nottingham-repository.worktribe.com/output/1132598
Publisher URL https://www.nature.com/articles/s41386-018-0171-0

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