Selective alpha 7 nicotinic receptor stimulation normalizes chronic cocaine-induced loss of hippocampal sensory inhibition in C3H mice

Background: A physiological alteration associated with schizophrenic and ma nic psychoses is diminished inhibition of the electrophysiological response to repeated auditory stimuli. This deficit also occurs in cocaine addicts. Studies in animals show that such inhibition is decreased by noradrenergic receptor stimulation and that the inhibition is enhanced by nicotinic chol inergic receptor stimulation. Methods: C3H mice were treated for 7 days with cocaine. They were then prep ared for electrophysiological recording. After the effects of cocaine treat ment were observed, they were treated with nicotine agonists. Results: Chronic cocaine administration markedly diminished inhibition of t he hippocampal-evoked response to repeated auditory stimuli. The loss of in hibition was reversed by acute treatment with either nicotine or the select ive alpha 7 nicotinic agonist 3-(2,4)-dimethoxybenzylidine anabaseine (DMXB ; GTS21). The effects of nicotine showed tachyphylaxis, whereas those of DM XB did not. Conclusions: This reversal of cocaine's effect by nicotinic agonists is con sistent with previous pharmacological studies of the inhibition of auditory response. Additionally, the ability of nicotinic agonists to reverse a phy siological defect associated with psychosis may have therapeutic implicatio ns for the neuropsychiatric sequelae of cocaine addiction in humans. Biol P sychiatry 1999;46: 1443-1450 (C) 1999 Society of Biological Psychiatry.