Chronic exposure to typical or atypical antipsychotics in rodents: temporal effects on central alpha7 nicotinic acetylcholine receptors

A decrease in alpha7 nicotinic acetylcholine receptors in the hippocampus has been hypothesized to contribute to alterations in auditory gating and other behavioral impairments in schizophrenia. However, while both typical and atypical neuroleptics are routinely used in the therapeutics of schizophr...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience 2005, Vol.136 (2), p.519-529
Main Authors: Terry, Jr, A V, Gearhart, D A, Mahadik, S P, Warsi, S, Davis, L W, Waller, J L
Format: Article
Language:English
Subjects:
Acoustic Stimulation
alpha7 Nicotinic Acetylcholine Receptor
Animals
Antipsychotic Agents - blood
Antipsychotic Agents - pharmacology
Autoradiography
Brain Chemistry - drug effects
Bungarotoxins - pharmacokinetics
Densitometry
Male
Rats
Rats, Wistar
Receptors, Nicotinic - drug effects
Reflex, Startle - drug effects
Time Factors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A decrease in alpha7 nicotinic acetylcholine receptors in the hippocampus has been hypothesized to contribute to alterations in auditory gating and other behavioral impairments in schizophrenia. However, while both typical and atypical neuroleptics are routinely used in the therapeutics of schizophrenia, little is known about their effects on auditory gating or alpha7 nicotinic acetylcholine receptor expression particularly when they are administered for extended periods of time (which is common in the clinical setting). In the present study in normal rats, the residual effects of prior chronic treatment (90 or 180 days) with representative typical and atypical neuroleptics (oral haloperidol, 2.0 mg/kg/day; chlorpromazine, 10.0 mg/kg/day, risperidone, 2.5 mg/kg/day; or olanzapine, 10.0 mg/kg/day) on prepulse inhibition of the auditory gating response were investigated. The densities of alpha7 nicotinic acetylcholine receptors were subsequently measured using [125I]-alpha-bungarotoxin autoradiography. The results indicated that none of the compounds significantly altered the startle amplitude or prepulse inhibition response either during drug treatment (day 60) or after 90 or 180 days of treatment (i.e. during a drug free washout). However, prior exposure to chlorpromazine, risperidone and olanzapine for 90 days resulted in modest but significant (P
ISSN:0306-4522