title: Exposure to predator odor and resulting anxiety enhances the expression of the α2 δ subunit of voltage-sensitive calcium channels in the amygdala.
abstract: The α2 δ subunit of voltage-sensitive calcium channels (VSCCs) is the molecular target of pregabalin and gabapentin, two drugs marked for the treatment of focal epilepsy, neuropathic pain, and anxiety disorders. Expression of the α2 δ subunit is up-regulated in the dorsal horns of the spinal cord in models of neuropathic pain, suggesting that plastic changes in the α2 δ subunit are associated with pathological states. Here, we examined the expression of the α2 δ-1 subunit in the amygdala, hippocampus, and frontal cortex in the trimethyltiazoline (TMT) mouse model of innate anxiety. TMT is a volatile molecule present in the feces of the rodent predator, red fox. Mice that show a high defensive behavior during TMT exposure developed anxiety-like behavior in the following 72 h, as shown by the light-dark test. Anxiety was associated with an increased expression of the α2 δ-1 subunit of VSCCs in the amygdaloid complex at all times following TMT exposure (4, 24, and 72 h). No changes in the α2 δ-1 protein levels were seen in the hippocampus and frontal cortex of mice exposed to TMT. Pregabalin (30 mg/kg, i.p.) reduced anxiety-like behavior in TMT-exposed mice, but not in control mice. These data offer the first demonstration that the α2 δ-1 subunit of VSCCs undergoes plastic changes in a model of innate anxiety, and supports the use of pregabalin as a disease-dependent drug in the treatment of anxiety disorders.
authors: Department of Physiology and Pharmacology, University Sapienza, Roma, Italy.
authors: Carla
authors: C
authors: Nasca
authors: Rosamaria
authors: R
authors: Orlando
authors: Moreno
authors: M
authors: Marchiafava
authors: Paolo
authors: P
authors: Boldrini
authors: Giuseppe
authors: G
authors: Battaglia
authors: Sergio
authors: S
authors: Scaccianoce
authors: Francesco
authors: F
authors: Matrisciano
authors: Anna
authors: A
authors: Pittaluga
authors: Ferdinando
authors: F
authors: Nicoletti
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000523:psychology; D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics; D005589:Foxes; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D009812:Odorants; D011235:Predatory Behavior / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C512066:CACNA2D1 protein, mouse; D015220:Calcium Channels