title: Midazolam treatment before re-exposure to contextual fear reduces freezing behavior and amygdala activity differentially in high- and low-anxiety rats.
abstract: The aim of this study was to examine the effects of benzodiazepine (midazolam) administration on rat conditioned fear responses and on local brain activity (c-Fos and CRF expressions) of low- (LR) and high- (HR)anxiety rats after the first and second contextual fear test sessions. The animals were divided into LR and HR groups based on the duration of their conditioned freezing response in the first contextual fear test. The fear-re-conditioned LR and HR animals (28 days later) had increased freezing durations compared with those durations during the first conditioned fear test. These behavioral effects were accompanied by increased c-Fos expression in the medial amygdala (MeA), the basolateral amygdala (BLA), and the paraventricular hypothalamic nuclei and elevated CRF expression in the MeA. All these behavioral and immunochemical effects of fear re-conditioning were stronger in the LR group compared with the effects in the HR group. Moreover, in the LR rats, the re-conditioning led to decreased CRF expression in the primary motor cortex (M1) and to increased CRF expression in the BLA. The pretreatment of rats with midazolam before the second exposure to the aversive context significantly attenuated the conditioned fear response, lowered the serum corticosterone concentration, decreased c-Fos and CRF expressions in the MeA and in the BLA, and increased CRF complex density in M1 area only in the LR group. These studies have demonstrated that LR rats are more sensitive to re-exposure to fear stimuli and that midazolam pretreatment was associated with modified brain activity in the amygdala and in the prefrontal cortex in this group of animals. The current data may facilitate a better understanding of the neurobiological mechanisms responsible for individual differences in the psychopathological processes accompanying some anxiety disorders characterized by stronger reactivity to re-exposure to stressful challenges, e.g., posttraumatic stress disorder.
authors.affiliation: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland. Electronic address: skorzews@ipin.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Skórzewska
authors.affiliation: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lehner
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, 1B Banacha Street, 02-097 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Wisłowska-Stanek
authors.affiliation: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Turzyńska
authors.affiliation: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Sobolewska
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, 1B Banacha Street, 02-097 Warsaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krząścik
authors.affiliation: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland; Department of Experimental and Clinical Pharmacology, Medical University, 1B Banacha Street, 02-097 Warsaw, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Płaźnik
mesh_terms: D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D003214:Conditioning, Classical; D003345:Corticosterone / Q000097:blood; D005239:Fear; D008874:Midazolam / Q000494:pharmacology*; D051381:Rats
chemical_list: D014151:Anti-Anxiety Agents; D008874:Midazolam; D003345:Corticosterone
keywords: Brain structures; Contextual fear re-conditioning; Individual differences; Midazolam; c-Fos and CRF immunocytochemistry