Reversal of diminished inhibitory sensory gating in cocaine addicts by a nicotinic cholinergic mechanism

Cocaine addiction, as with other stimulant abuse, produces psychotic sympto ms. Although often moderate to mild in severity, these symptoms are, nevert heless, associated with poorer over-all outcome. Recent studies suggest dim inished nicotinic cholinergic neurotransmission as a mechanism of a physiol ogical deficit found in schizophrenia, failure of auditory sensory inhibiti on. Diminished inhibitory sensory gating also occurs in cocaine addicts, pr obably because of their increased catecholamingeric neurotransmission, whic h blocks the inhibition. In the present study, 11 cocaine addicts in the fi rst week of detoxification were recorded electrophysiologically, after whic h the effects of 6 mg of nicotine gum, were assessed in a double-blind plac ebo-controlled crossover design. The test was repeated 10 days later. Treat ment with nicotine, but not placebo, briefly reversed the inhibitory abnorm ality on both test days. Although nicotine itself may not be a desirable th erapeutic agent, because desensitization of nicotinic receptors limits the time course of its effect, the study identifies a previously unexploited th erapeutic target for new drug development of the neuropsychiatric sequelae of cocaine addition. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.