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DMXB, an α7 nicotinic agonist, normalizes auditory gating in isolation-reared rats

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Abstract

Rationale

Impaired auditory gating is common in schizophrenic patients. Evidence suggests that this deficit is related to a reduced number of α7 nicotinic receptors and therefore treatment with α7 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.

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Acknowledgements

This study was supported by a VA Merit Award (K.E.S.), and an NIMH USPHS Grant MH58680 (K.E.S.).

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Authors and Affiliations

  1. Medical Research Service, Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80020, USA

    Karen E. Stevens

  2. Department of Psychiatry C268-71, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA

    Heidi C. O'Neill, Kate Rieger & Karen E. Stevens

  3. Department of Pharmacology and Experimental Therapeutics, University of Florida, Gainesville, Fla., USA

    William R. Kem

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  1. Heidi C. O'Neill
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  2. Kate Rieger
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  3. William R. Kem
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  4. Karen E. Stevens
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Correspondence to Karen E. Stevens.

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O'Neill, H.C., Rieger, K., Kem, W.R. et al. DMXB, an α7 nicotinic agonist, normalizes auditory gating in isolation-reared rats. Psychopharmacology 169, 332–339 (2003). https://doi.org/10.1007/s00213-003-1482-2

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  • DOI: https://doi.org/10.1007/s00213-003-1482-2

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