Anti-ADRA1A (aa 1-27) polyclonal antibody

Rationale Recovery from a traumatic experience requires extinction of cue-based fear responses, a process that is impaired in post-traumatic stress disorder. While studies suggest a link between fear behavioral flexibility and noradrenaline signaling, the role of specific receptors and brain regions in these effects is unclear. Objectives Here, we examine the role of prazosin, an 1-adrenergic receptor (1-AR) antagonist, in auditory fear conditioning and extinction. Methods C57Bl/6N mice were subjected to auditory fear conditioning and extinction in combination with systemic (0.1-2mg/kg) or local microinjections (3 or 6mM) of the 1-AR antagonist prazosin into the prelimbic division of medial prefrontal cortex or basolateral amygdala. Conditioned fear and anxiety-like behaviors were compared with vehicle-injected control animals. Results Mice that received systemic prazosin prior to fear conditioning exhibited similar initial levels of cue-elicited freezing compared to vehicle controls on the following day. However, at all doses tested, fear that was acquired during prazosin treatment was more readily extinguished, whereas anxiety-like behavior on the day of extinction was unaffected. A similar pattern of results was observed when prazosin was microinjected into the basolateral amygdala but not the prelimbic cortex. In contrast to pre-conditioning injections, prazosin administration prior to extinction had no effect on freezing. Conclusions Our results indicate that 1-AR activity during aversive conditioning is dispensable for memory acquisition but renders conditioned fear more impervious to extinction. This suggests that behavioral flexibility is constrained by noradrenaline at the time of initial learning via activation of a specific AR isoform.

Epigenetic regulation may be involved in the pathophysiology of mental disorders, such as schizophrenia and bipolar disorder, and in the pharmacological action of drugs. Characterizing the epigenetic effects of drugs is an important step to optimal treatment. We performed comprehensive and gene-specific DNA methylation analyses of quetiapine using human neuroblastoma cells. Human neuroblastoma cells were cultured with quetiapine for 8 days, and DNA methylation analysis was performed using Infinium HumanMethylation27 BeadChip. A total of 1173 genes showed altered DNA methylation. Altered DNA methylation predominantly occurred as hypomethylation within the CpG island compared to DNA isolated from non-treated cells. Gene ontology analysis revealed that these genes were related to the cellular process of intracellular protein binding. There was no common effect of quetiapine with three mood stabilizers (lithium, valproate, and carbamazepine). However, common DNA methylation changes in eight genes, including ADRA1A, which encodes adrenoceptor alpha 1A, were found with quetiapine and lithium treatments. Finally, bisulfite-sequencing analysis revealed that quetiapine decreased the DNA methylation level of the promoter region of SLC6A4, where hypermethylation with bipolar disorder and hypomethylation with mood stabilizers have been reported. (C) 2014 Elsevier Inc. All rights reserved.