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Chronic Methamphetamine Self‐Administration Dysregulates Oxytocin Plasma Levels and Oxytocin Receptor Fibre Density in the Nucleus Accumbens Core and Subthalamic Nucleus of the Rat
Author(s) -
Baracz S. J.,
Parker L. M.,
Suraev A. S.,
Everett N. A.,
Goodchild A. K.,
McGregor I. S.,
Cornish J. L.
Publication year - 2016
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12337
Subject(s) - meth , oxytocin , nucleus accumbens , methamphetamine , medicine , oxytocin receptor , endocrinology , self administration , extinction (optical mineralogy) , neuropeptide , chemistry , psychology , receptor , mineralogy , monomer , organic chemistry , acrylate , polymer
The neuropeptide oxytocin attenuates reward and abuse for the psychostimulant methamphetamine ( METH ). Recent findings have implicated the nucleus accumbens ( NA c) core and subthalamic nucleus ( ST h) in oxytocin modulation of acute METH reward and relapse to METH ‐seeking behaviour. Surprisingly, the oxytocin receptor ( OTR ) is only modestly involved in both regions in oxytocin attenuation of METH ‐primed reinstatement. Coupled with the limited investigation of the role of the OTR in psychostimulant‐induced behaviours, we primarily investigated whether there are cellular changes to the OTR in the NA c core and ST h, as well as changes to oxytocin plasma levels, after chronic METH i.v. self‐administration ( IVSA ) and after extinction of drug‐taking. An additional aim was to examine whether changes to central corticotrophin‐releasing factor ( CRF ) and plasma corticosterone levels were also apparent because of the interaction of oxytocin with stress‐regulatory mechanisms. Male Sprague–Dawley rats were trained to lever press for i.v. METH (0.1 mg/kg/infusion) under a fixed‐ratio 1 schedule or received yoked saline infusions during 2‐h sessions for 20 days. An additional cohort of rats underwent behavioural extinction for 15 days after METH IVSA . Subsequent to the last day of IVSA or extinction, blood plasma was collected for enzyme immunoassay, and immunofluorescence was conducted on NA c core and ST h coronal sections. Rats that self‐administered METH had higher oxytocin plasma levels, and decreased OTR ‐immunoreactive (‐IR) fibres in the NA c core than yoked controls. In animals that self‐administered METH and underwent extinction, oxytocin plasma levels remained elevated, OTR ‐IR fibre density increased in the ST h, and a trend towards normalisation of OTR ‐IR fibre density was evident in the NA c core. CRF ‐IR fibre density in both brain regions and corticosterone plasma levels did not change across treatment groups. These findings demonstrate that oxytocin systems, both centrally within the NA c core and ST h, as well as peripherally through plasma measures, are dysregulated after METH abuse.