RT Journal Article SR Electronic T1 Chronic Cocaine Administration Switches Corticotropin-Releasing Factor2 Receptor-Mediated Depression to Facilitation of Glutamatergic Transmission in the Lateral Septum JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 577 OP 583 DO 10.1523/JNEUROSCI.4196-04.2005 VO 25 IS 3 A1 Jie Liu A1 Baojian Yu A1 Luis Orozco-Cabal A1 Dimitri E. Grigoriadis A1 Jean Rivier A1 Wylie W. Vale A1 Patricia Shinnick-Gallagher A1 Joel P. Gallagher YR 2005 UL http://www.jneurosci.org/content/25/3/577.abstract AB Corticotropin-releasing factor (CRF) and urocortin (Ucn I) are endogenous members among a family of CRF-related peptides that activate two different and synaptically localized G-protein-coupled receptors, CRF1 and CRF2. These peptides and their receptors have been implicated in stress responses and stress with cocaine abuse. In this study, we observed significant alterations in excitatory transmission and CRF-related peptide regulation of excitatory transmission in the lateral septum mediolateral nucleus (LSMLN) after chronic cocaine administration. In brain slice recordings from the LSMLN of control (saline-treated) rats, glutamatergic synaptic transmission was facilitated by activation of CRF1 receptors with CRF but was depressed after activation of CRF2 receptors with Ucn I. After acute withdrawal from a chronic cocaine administration regimen, CRF1 activation remained facilitatory, but CRF2 activation facilitated rather than depressed LSMLN EPSCs. These alterations in CRF2 effects occurred through both presynaptic and postsynaptic mechanisms. In saline-treated rats, CRF1 and CRF2 coupled predominantly to protein kinase A signaling pathways, whereas after cocaine withdrawal, protein kinase C activity was more prominent and likely contributed to the CRF2-mediated presynaptic facilitation. Neither CRF nor Ucn I altered monosynaptic GABAA-mediated IPSCs before or after chronic cocaine administration, suggesting that loss of GABAA-mediated inhibition could not account for the facilitation. This switch in polarity of Ucn I-mediated neuromodulation, from a negative to positive regulation of excitatory glutamatergic transmission after chronic cocaine administration, could generate an imbalance in the brain reward circuitry associated with the LSMLN.