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 manic 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 cholinergic receptor stimulation.


METHODS
C3H mice were treated for 7 days with cocaine. They were then prepared for electrophysiological recording. After the effects of cocaine treatment were observed, they were treated with nicotine agonists.


RESULTS
Chronic cocaine administration markedly diminished inhibition of the hippocampal-evoked response to repeated auditory stimuli. The loss of inhibition was reversed by acute treatment with either nicotine or the selective alpha 7 nicotinic agonist 3-(2,4)-dimethoxybenzylidine anabaseine (DMXB; GTS21). The effects of nicotine showed tachyphylaxis, whereas those of DMXB did not.


CONCLUSIONS
This reversal of cocaine's effect by nicotinic agonists is consistent with previous pharmacological studies of the inhibition of auditory response. Additionally, the ability of nicotinic agonists to reverse a physiological defect associated with psychosis may have therapeutic implications for the neuropsychiatric sequelae of cocaine addiction in humans.
Stevens
K E
KE
Department of Psychiatry, University of Colorado Health Sciences Center, Denver 80262, USA.
Kem
W R
WR
Freedman
R
R
D000818:Animals; D001307:Auditory Perception / Q000187:drug effects*; D002908:Chronic Disease; D019970:Cocaine-Related Disorders / Q000150:complications*; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009433:Neural Inhibition / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010468:Perceptual Disorders / Q000209:etiology* / Q000503:physiopathology*; D011950:Receptors, Cholinergic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects*
D018722:Nicotinic Agonists; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D009538:Nicotine