Intragastric DMXB-A, an alpha 7 nicotinic agonist, improves deficient sensory inhibition in DBA/2 mice

Background: Abnormal sensory inhibition is observed in the majority of schi zophrenic patients. DBA/2 mice spontaneously exhibit a similar deficit in s ensory inhibition and thus provide a model for drug development targeted to this physiologic abnormality. The impaired sensory inhibition is character ized by diminished response of the hippocampal evoked potential to the seco nd of closely paired auditory stimuli (500-m/sec interstimulus interval). S ubnormal levels of hippocampal alpha7 nicotinic cholinergic receptors are a ssociated with the deficient sensory inhibition in both DBA/2 mice and peop le with schizophrenia. Methods: Our study examined the inhibition of the P20-N40 auditory evoked p otential in DBA/2 mice after intragastric administration of DMXB-A (3-2,4-d imethoxybenzylidine anabaseine), an alpha7 nicotinic receptor partial agoni st. After presentation of auditory stimuli, electroencephalographic respons es were recorded and measured to monitor the effects of the DMXB-A, alone a nd in combination with selective nicotinic antagonists. Results: Gastric administration of DMXB-A (10 mg/kg) improved sensory inhib ition in DBA/2 mice. This improvement was blocked by alpha -bungarotoxin, b ut not mecamylamine, indicating that DMXB-A exerts its effects through the alpha7 nicotinic receptor. Conclusions: Intragastrically administered DMXB-A improves deficient sensor y, inhibition in DBA/2 mice through stimulation of alpha7 nicotinic recepto rs. These studies agree with results from previous studies with subcutaneou sly administered DMXB-A. Biol Psychiatry 2001; 50:493-500 (C) 2001 Society of Biological Psychiatry.