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

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 microdia...

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Main Authors: Kohli, Shivali, King, Madeleine V., Williams, Stuart, Edwards, Adele, Ballard, Theresa M., Steward, Lucinda J., Alberati, Daniella, Fone, Kevin C.F.
Format: Article
Language:English
English
Published: Nature Publishing Group 2018
Online Access:https://eprints.nottingham.ac.uk/53168/
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author Kohli, Shivali
King, Madeleine V.
Williams, Stuart
Edwards, Adele
Ballard, Theresa M.
Steward, Lucinda J.
Alberati, Daniella
Fone, Kevin C.F.
author_facet Kohli, Shivali
King, Madeleine V.
Williams, Stuart
Edwards, Adele
Ballard, Theresa M.
Steward, Lucinda J.
Alberati, Daniella
Fone, Kevin C.F.
author_sort Kohli, Shivali
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-531682019-02-07T04:30:14Z https://eprints.nottingham.ac.uk/53168/ 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. 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. Nature Publishing Group 2018-08-07 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/53168/1/Fone%20Oxytocin%20MS%20Revised2withFigAAM%20version.pdf application/pdf en https://eprints.nottingham.ac.uk/53168/2/Oxytocin%20MS_%20Supplementary%20FiguresAAM%20version.pdf Kohli, Shivali, King, Madeleine V., Williams, Stuart, Edwards, Adele, Ballard, Theresa M., Steward, Lucinda J., 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 https://www.nature.com/articles/s41386-018-0171-0 doi:10.1038/s41386-018-0171-0 doi:10.1038/s41386-018-0171-0
spellingShingle Kohli, Shivali
King, Madeleine V.
Williams, Stuart
Edwards, Adele
Ballard, Theresa M.
Steward, Lucinda J.
Alberati, Daniella
Fone, Kevin C.F.
Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
title Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
title_full Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
title_fullStr Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
title_full_unstemmed Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
title_short Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
title_sort oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
url https://eprints.nottingham.ac.uk/53168/
https://eprints.nottingham.ac.uk/53168/
https://eprints.nottingham.ac.uk/53168/