Prodynorphin gene deletion increased anxiety-like behaviours, impaired the anxiolytic effect of bromazepam and altered GABAA receptor subunits gene expression in the amygdala.
This study evaluated the role of prodynorphin gene in the regulation of anxiety and associated molecular mechanisms. Emotional responses were assessed using the light-dark test, elevated plus maze and social interaction tests in prodynorphin knockout and wild-type mice. Corticotrophin releasing factor and proopiomelanocortin gene expressions in the hypothalamus were evaluated after restraint stress using in situ hybridization. The anxiolytic efficacy of bromazepam and GABA(A) receptor subunits gene expression in the amygdala were also assessed in both genotypes. The deletion of prodynorphin increased anxiety-like behaviours and proopiomelanocortin gene expression in the arcuate nucleus (two-fold). Moreover, the anxiolytic action of bromazepam was significantly attenuated in the mutant mice. Decreased GABA(A)γ(2) and increased GABA(A)β(2) gene expression receptor subunits were found in the amygdala of prodynorphin knockout mice. These results indicate that deletion of prodynorphin gene is associated with increased anxiety-like behaviours, enhanced sensibility response to stress stimuli, reduced anxiolytic efficacy of bromazepam and altered expression of the GABA(A) receptor subunits.
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, Spain.
Teresa
T
Femenía
Sandra
S
Pérez-Rial
Leyre
L
Urigüen
Jorge
J
Manzanares
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism; D001960:Bromazepam / Q000494:pharmacology*; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects
D014151:Anti-Anxiety Agents; D004745:Enkephalins; D011498:Protein Precursors; D011963:Receptors, GABA-A; C033660:preproenkephalin; D001960:Bromazepam