The influence of CRF2 receptor antagonists on rat conditioned fear responses and c-Fos and CRF expression in the brain limbic structures Anna Skórzewska1, Ma³gorzata Lehner1, Adam Hamed1,2, Aleksandra Wis³owska-Stanek2, Danuta Turzyñska1, Alicja Sobolewska1, Adam P³aŸnik1,2 Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego 9, PL 02-957 Warszawa, Poland; Department of Experimental and Clinical Pharmacology, Medical University, Krakowskie Przedmiecie 26/28, PL 00-927 Warszawa, Poland The aim of this study was to examine the influence of intracerebroventricular-administered selective corticotropin-releasing factor receptor 2 (CRF2) antagonists (antisauvagine-30, astressin-2B), on rat conditioned fear responses, expression levels of c-Fos and CRF, and plasma corticosterone concentration. In fear-conditioned animals, both CRF receptor antagonists enhanced a conditioned freezing fear response and increased the conditioned fear-elevated concentration of serum corticosterone. Exogenously administered antisauvagine-30 increased the aversive context-induced expression of c-Fos in the 1 and 2 areas of the cingulate cortex (Cg1, Cg2), the central amygdala (CeA) and parvocellular neurons of the
paraventricular hypothalamic nucleus (pPVN). Immunocytochemistry demonstrated an increase in CRF expression in the Cg1, M2 areas of the cortex, and pPVN, and it revealed the effect of conditioned fear in the CeA 35 min after antisauvagine-30 administration and 10 min after the conditioned fear test. Furthermore, astressin-2B, another CRF2 receptor antagonist, enhanced expression of c-Fos and CRF in the CeA and pPVN, and revealed the effect of conditioned fear in the Cg1. These data support a model in which an excess in CRF1 receptor activation, combined with reduced CRF2 receptor signaling, may contribute to stronger expression of anxiety-like responses.
The effects of D-cycloserine and midazolam on the expression of alpha-2 subunit of GABA-A receptor and gephyrin of high and low anxiety rats Aleksandra Wis³owska-Stanek1, Ma³gorzata Lehner2, Anna Skórzewska2, Danuta Turzyñska2, Alicja Sobolewska2, Adam P³aŸnik1,2 Department of Experimental and Clinical Pharmacology, Medical University, Krakowskie Przedmiecie 26/28, PL 00-927 Warszawa, Poland; Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego 9, PL 02-957 Warszawa, Poland We investigated how D-cycloserine and midazolam affect the behavior and expression of alpha-2 subunit of GABA-A receptor and gephyrin in brain structures of high and low anxiety rats during extinction session of conditioned fear test. High (HR) and low (LR) anxiety rats, were selected according to their behavior in the contextual fear test (i.e., the duration of a freezing response was used as a discriminating variable). Administration of D-cycloserine (15 mg/kg, ip), sig562
Pharmacological Reports, 2011, 63, 560588
nificantly enhanced the inhibition of an aversive context-induced freezing response observed during the extinction session in HR and LR rats 7 days after contextual fear test. In contrast, midazolam (0.75 mg/kg, ip), accelerated the attenuation of fear responses only in HR rats. HR rats pretreated with saline had higher expression of alpha-2 subunits of GABA-A receptor in basolateral amygdala (BLA) compared to LR rats. Administration of D-cycloserine and midazolam in-