Enhanced psychostimulant response, but not social avoidance, depends on GluA1 AMPA receptors in VTA dopamine neurons following intermittent social defeat stress in rats. (14th July 2020)

• Record Type: Journal Article
• Authors: Rudolph, Megan L.; Neve, Racheal L.; Hammer, Ronald P.; Nikulina, Ella M.
• Other Names: Schmidt Mathias V. guestEditor.; Robinson Oliver guestEditor.; Sandi Carmen guestEditor.
• Is Part Of: European journal of neuroscience. Volume 55:Number 9/10(2022)
• Page Start: 2154
• Page End: 2169
• Publication Date: 2020-07-14
• Subjects: amphetamine cross‐sensitization -- glutamate signalling -- mesolimbic -- TH‐Cre rats -- viral‐mediated gene transfer; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.14884
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Evidence from both human and animal studies demonstrates the importance of social stress in the development of addiction‐related behaviour. In rats, intermittent social defeat stress causes long‐lasting psychostimulant cross‐sensitization. Our recent data reveal heightened expression of AMPA receptor (AMPAR) GluA1 subunit in rat ventral tegmental area (VTA), which occurs concurrently with social stress‐induced amphetamine (AMPH) cross‐sensitization. In addition, social stress in rats induced social avoidance behaviour. The present study evaluated the effects of intermittent social defeat stress on GluA1 expression in VTA dopamine (DA) neurons, then utilized Cre‐dependent virus‐mediated gene transfer to determine the functional role of homomeric GluA1‐AMPARs in these neurons. Social defeat stress exposure induced GluA1 expression in VTA DA neurons, as demonstrated by a greater density of GluA1/tyrosine hydroxylase (TH) double‐labelling in VTA neurons in stressed rats. Additionally, functional inactivation of VTA GluA1 AMPARs in DA neurons prevented stress‐induced cross‐sensitization, or augmented locomotor response to low dose AMPH challenge (1.0 mg/kg, i.p.), but had no effect on social stress‐induced social avoidance behaviour. Furthermore, wild‐type overexpression of GluA1 in VTA DA neurons had the opposite effect; locomotor‐activating effects of AMPH were significantly augmented, even in the absence of stress. Taken together, these results suggest that stress‐induced GluA1 expression in VTA DA neurons is necessary for psychostimulant cross‐sensitization, but not for social avoidance. This differential effect suggests that different neural pathways are implicated in these behaviours. These findings could lead to novel pharmacotherapies to help prevent stress‐induced susceptibility to substance abuse. Abstract : Functional inactivation of GluA1‐homomeric AMPA receptors in VTA dopamine neurons of TH‐Cre rats prevents social stress‐induced sensitization to amphetamine, but has no effect on stress‐induced social avoidance behavior. Overexpression of GluA1‐homomeric AMPA receptors in VTA dopamine neurons of TH‐Cre rats mimics the effects of social stress on amphetamine sensitivity, inducing augmented locomotor activity following low‐dose amphetamine challenge.