The role of afferents to the locus coeruleus in the handling stress-induced increase in the release of noradrenaline in the medial prefrontal cortex: a dual-probe microdialysis study in the rat brain

This study was aimed to identify the neuronal pathways that mediate the handling stress-induced increase in the release of noradrenaline in the medial prefrontal cortex of the rat brain. For that purpose a microdialysis probe was implanted in the vicinity of the locus coeruleus and a second probe was placed in the ipsilateral medial prefrontal cortex. Receptor specific antagonists acting on the alpha(2)-adrenoceptor (50 mu M idazoxan), GABA(A) (50 mu M bicuculline), GABA(B) (100 mu M (3,4-Dichlorophenyl)methyl]propyl](diethoxymethyl) phosphonic acid; CGP 52432), acetylcholine (10 mu M atropine), corticotropin releasing factor (CRF) (100 mu M butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-7H- pyrrolo[2,3-d]pyrimidin-4-yl]-amine; CP-154,526), NMDA glutamate (300 mu M (+/-)-3(2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid; CPP) and non-NMDA glutamate receptors (500 mu M 6,7-dinitroquinoxaline-2,3-dione; DNQX) were infused into the locus coeruleus by retrograde dialysis, whereas extracellular noradrenaline was recorded in the ipsilateral medial prefrontal cortex. During infusion of the various compounds rats were gently handled for 10 min. Infusion of idazoxan potentiates the handling-induced increase in the release of noradrenaline in the medial prefrontal cortex. The infusions of, atropine, bicuculline, CGP 52432 and DNQX were without effect on the handling response. Infusion of the NMDA receptor antagonist CPP or the non-peptide CRF receptor antagonist CP-154,526 suppressed the stimulation of noradrenaline during stress. It is concluded that alpha(2)-adrenoceptors, NMDA glutamate receptors and CRF receptors modify the handling stress response of locus coeruleus neurones. The data suggest no major role for glutamatergic, GABAergic, or cholinergic afferents to the locus coeruleus in mediating the stress response. (C) 2000 Elsevier Science B.V. All rights reserved.