Chronic corticosterone treatment alters sensory gating in C3H mice

Two methods of evaluating inhibitory sensory processing are prepulse inhibi tion of acoustic startle (PPI) and gating of auditory evoked potentials. St udies using both methods suggest nicotinic acetylcholinergic receptor modul ation of gating, specifically the alpha -bungarotoxin (alpha -BTX) binding site (alpha7 receptor subtype). However, recent assessment of alpha7 null m utant mice failed to demonstrate any effect of the loss of this receptor in either gating paradigm. An alternate approach to assessing the effects of the alpha7 receptor is to reduce its numbers in mature inbred mice, thus, a voiding the twin problems of background and developmental compensation inhe rent in null mutant mouse studies. Numerous studies have shown that chronic corticosterone (CCS) treatment selectively reduces alpha -BTX binding site s. C3H mice were adrenalectomized and implanted with corticosterone or chol esterol (control) pellets. After 8 days, they were tested in one of the gat ing paradigms. PPI and auditory gating were significantly diminished in cor ticosterone-treated mice concomitant with a reduction in alpha -BTX binding in several brain regions. Cholesterol-treated mice had no change in either paradigm. Nicotine treatment (1 mg/kg) produced significant improvement in both paradigms in corticosterone-treated mice. These data agree with previ ous pharmacological studies suggesting modulation of gating occurs through a nicotinic receptor. (C) 2001 Elsevier Science Inc. All rights reserved.