Journal
BIOLOGICAL PSYCHIATRY
Volume 50, Issue 7, Pages 493-500Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0006-3223(01)01093-9
Keywords
schizophrenia; sensory gating; auditory gating; hippocampal auditory evoked response; DMXB-A (a.k.a. GTS-21); nicotinic receptor
Categories
Funding
- NIMH NIH HHS [MH44211, MH58680] Funding Source: Medline
Ask authors/readers for more resources
Background: Abnormal sensory inhibition is observed in the majority of schizophrenic patients. DBA/2 mice spontaneously exhibit a similar deficit in sensory inhibition and thus provide a model for drug development targeted to this physiologic abnormality. The impaired sensory inhibition is characterized by diminished response of the hippocampal evoked potential to the second of closely paired auditory stimuli (500-m/sec interstimulus interval). Subnormal levels of hippocampal alpha7 nicotinic cholinergic receptors are associated with the deficient sensory inhibition in both DBA/2 mice and people with schizophrenia. Methods: Our study examined the inhibition of the P20-N40 auditory evoked potential in DBA/2 mice after intragastric administration of DMXB-A (3-2,4-dimethoxybenzylidine anabaseine), an alpha7 nicotinic receptor partial agonist. After presentation of auditory stimuli, electroencephalographic responses were recorded and measured to monitor the effects of the DMXB-A, alone and in combination with selective nicotinic antagonists. Results: Gastric administration of DMXB-A (10 mg/kg) improved sensory inhibition in DBA/2 mice. This improvement was blocked by alpha -bungarotoxin, but not mecamylamine, indicating that DMXB-A exerts its effects through the alpha7 nicotinic receptor. Conclusions: Intragastrically administered DMXB-A improves deficient sensory, inhibition in DBA/2 mice through stimulation of alpha7 nicotinic receptors. These studies agree with results from previous studies with subcutaneously administered DMXB-A. Biol Psychiatry 2001; 50:493-500 (C) 2001 Society of Biological Psychiatry.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available