Dysfunctional inhibitory mechanisms in locus coeruleus neurons of the Wistar Kyoto rat

Bruzos, C. , Ugedo, L. & Torrecilla, M.

Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, 48940 Leioa, Spain.

The Locus coeruleus (LC) nucleus is widely implicated in depression. In addition to glutamatergic and GABAergic synaptic inputs, activation of ?2-adrenoceptors mainly regulates LC activity. The goal of this study was to investigate the sensitivity of ?2-adrenoceptors, as well as glutamatergic and GABAergic synaptic activity of LC neurons from the Wistar Kyoto (WKY) rat, an animal model of depression, using patch-clamp whole-cell recordings. The ?2-adrenoceptors from WKY rats were less sensitive to the agonist, UK than those from Wistar control rats. Beside a shorter rise time of the sEPSC no other significant alterations were detected in glutamatergic transmission of LC neurons from WKY. However, the GABAergic input was significantly altered in WKY rats, since sIPSC displayed reduced amplitude and increased half-width. These results point out that the inhibitory control exerted by ?2-adrenoceptors and GABAergic input onto LC neurons is dysregulated in WKY rats. This study highlights the mechanisms underlying altered neurotransmission in the LC of WKY rats, supporting the hypothesis that claims an unbalance between the glutamatergic-GABAergic systems as a key factor in the pathophysiology of depression.
Supported by FIS PI12/00613, Basque Government IT747-13 and University of the Basque Country UFI 11/12. C Bruzos has a grant from UPV/EHU.