Interhemispheric regulation of the rat medial prefrontal cortical glutamate stress response: role of local GABA- and dopamine-sensitive mechanisms.

TitleInterhemispheric regulation of the rat medial prefrontal cortical glutamate stress response: role of local GABA- and dopamine-sensitive mechanisms.
Publication TypeJournal Article
Year of Publication2017
AuthorsLupinsky D, Moquin L, Gratton A
JournalPsychopharmacology (Berl)
Volume234
Issue3
Pagination353-363
Date Published2017 Feb
ISSN1432-2072
Abstract

RATIONALE: We previously reported that stressors increase medial prefrontal cortex (PFC) glutamate (GLU) levels as a result of activating callosal neurons located in the opposite hemisphere and that this PFC GLU stress response is regulated by GLU-, dopamine- (DA-), and GABA-sensitive mechanisms (Lupinsky et al. 2010).OBJECTIVES: Here, we examine the possibility that PFC DA regulates the stress responsivity of callosal neurons indirectly by acting at D1 and D2 receptors located on GABA interneurons.METHODS: Microdialysis combined with drug perfusion (reverse dialysis) or microinjections was used in adult male Long-Evans rats to characterize D1, D2, and GABAB receptor-mediated regulation of the PFC GABA response to tail-pinch (TP) stress.RESULTS: We report that TP stress reliably elicited comparable increases in extracellular GABA in the left and right PFCs. SCH23390 (D1 antagonist; 100 μM perfusate concentration) perfused by reverse microdialysis attenuated the local GABA stress responses equally in the left and right PFCs. Intra-PFC raclopride perfusion (D2 antagonist; 100 μM) had the opposite effect, not only potentiating the local GABA stress response but also causing a transient elevation in basal (pre-stress) GABA. Moreover, unilateral PFC raclopride microinjection (6 nmol) attenuated the GLU response to TP stress in the contralateral PFC. Finally, intra-PFC baclofen perfusion (GABAB agonist; 100 μM) inhibited the local GLU and GABA stress responses.CONCLUSIONS: Taken together, these findings implicate PFC GABA interneurons in processing stressful stimuli, showing that local D1, D2, and GABAB receptor-mediated changes in PFC GABA transmission play a crucial role in the interhemispheric regulation of GLU stress responsivity.

DOI10.1007/s00213-016-4468-6
Alternate JournalPsychopharmacology (Berl.)
PubMed ID27822602

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