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



Here, we examine the possibility that PFC DA regulates the stress responsivity of callosal neurons indirectly by acting at D1and D2receptors located on GABA interneurons.



Microdialysis combined with drug perfusion (reverse dialysis) or microinjections was used in adult male Long-Evans rats to characterize D1, D2, and GABABreceptor-mediated regulation of the PFC GABA response to tail-pinch (TP) stress.



We report that TP stress reliably elicited comparable increases in extracellular GABA in the left and right PFCs. SCH23390 (D1antagonist; 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 (D2antagonist; 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 (GABABagonist; 100 μM) inhibited the local GLU and GABA stress responses.



Taken together, these findings implicate PFC GABA interneurons in processing stressful stimuli, showing that local D1, D2, and GABABreceptor-mediated changes in PFC GABA transmission play a crucial role in the interhemispheric regulation of GLU stress responsivity.
Department of Psychiatry, McGill University, Montréal, Québec, H4H 1R3, Canada. derek.lupinsky@douglas.mcgill.ca.|Douglas Institute Research Center, 6875 LaSalle Blvd, Montréal, Québec, H4H 1R3, Canada. derek.lupinsky@douglas.mcgill.ca.
Derek
D
Lupinsky
Douglas Institute Research Center, 6875 LaSalle Blvd, Montréal, Québec, H4H 1R3, Canada.
Luc
L
Moquin
Department of Psychiatry, McGill University, Montréal, Québec, H4H 1R3, Canada.|Douglas Institute Research Center, 6875 LaSalle Blvd, Montréal, Québec, H4H 1R3, Canada.
Alain
A
Gratton
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003337:Corpus Callosum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D007839:Functional Laterality; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D018080:Receptors, GABA-B; D013315:Stress, Psychological / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001552:Benzazepines; C000607792:DRD2 protein, rat; D018492:Dopamine Antagonists; D058786:GABA-B Receptor Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018080:Receptors, GABA-B; C534628:SCH 23390; D018698:Glutamic Acid; D020891:Raclopride; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D004298:Dopamine
Baclofen; Callosal neurons; GABA; Hemispheric specialization; Raclopride; SCH23390