DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared rats

Abstract

Rationale: Impaired auditory gating is common in schizophrenic patients. Evidence suggests that this deficit is related to a reduced number of alpha(7) nicotinic receptors and therefore treatment with alpha(7) nicotinic agonists may improve this condition. 3-(2,4)-Dimethoxybenzylidine anabaseine (DMXB; also known as GTS-21) is such an agonist and has shown efficacy in mice both orally and intraperitoneally.

Objective: Rats reared in social isolation post weaning have demonstrated a deficit in auditory gating similar to that seen in schizophrenia patients. The current study determined the effects of DMXB on auditory gating in awake, freely moving rats, comparing a group born and raised in-house and reared in isolation post-weaning (isolation reared) with a group shipped from the supplier as adults and housed in groups prior to surgery (controls).

Methods: Ten unmedicated, baseline recordings were obtained following surgical implantation of a recording electrode. All control group rats and the isolation-reared rats that showed deficient gating at baseline were treated with 1.0, 3.33, 10 or 33 mg/kg DMXB, IP, to determine the drug's impact on auditory gating.

Results: Isolation-reared rats had significantly improved auditory gating at the 3.33, 10 and 33 mg/kg doses, while control rats had a significant impairment in their auditory gating at the 33 mg/kg dose.

Conclusions: DMXB improved the auditory gating deficit seen in isolation-reared rats. As previously observed in another model, the change was produced through a decrease in the test amplitude in isolation-reared animals. Control animals had a significant reduction in conditioning amplitude at the high dose, which produced the loss of auditory gating. The results in the isolation-reared rats are in concert with previous studies which found similar improvement in auditory gating following administration of DMXB to DBA mice, the only differences being in the duration of the effect.