Chronic treatment with first or second generation antipsychotics in rodents: Effects on high affinity nicotinic and muscarinic acetylcholine receptors in the brain

• Published in: Neuroscience 2006-01, Vol.140 (4), p.1277-1287
• Main Authors: Terry, A.V., Gearhart, D.A., Mahadik, S.P., Warsi, S., Waller, J.L.
• Format: Article
• Language: English
• Subjects: Animals; Antipsychotic Agents - administration & dosage; Biological and medical sciences; Brain - drug effects; Brain - metabolism; chlorpromazine; cognition; Fundamental and applied biological sciences. Psychology; haloperidol; Male; Medical sciences; Neuropharmacology; olanzapine; Pharmacology. Drug treatments; Protein Binding - drug effects; Protein Binding - physiology; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Receptors, Muscarinic - metabolism; Receptors, Nicotinic - metabolism; risperidone; schizophrenia; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2006.03.011

Several postmortem and neuroimaging studies suggest that central nicotinic and muscarinic acetylcholine receptors are important in both the pathophysiology and pharmacotherapy of schizophrenia. However, while antipsychotic drugs are routinely used in the therapeutics of schizophrenia, little is known about their effects on the densities of these receptors when they are administered for extended periods of time (a common practice in the clinical setting). In the present study in rats, the residual effects of prior chronic exposure to representative first generation antipsychotics and second generation antipsychotics on the densities of high affinity nicotinic acetylcholine receptors and muscarinic acetylcholine receptor in the brain were investigated. Test subjects were treated with the first generation antipsychotics, haloperidol (2.0 mg/kg/day) or chlorpromazine (10.0 mg/kg/day) or the second generation antipsychotics, risperidone (2.5 mg/kg/day) or olanzapine (10.0 mg/kg/day) in drinking water for periods of 90 or 180 days, given a drug-free washout period (i.e. returned to normal drinking water) for two weeks and then killed. Quantitative receptor autoradiography was subsequently performed using 16 μm sagittal slices of whole brain incubated with [ 3H]-epibatidine, [ 3H]-pirenzepine or [ 3H]-AFDX-384 to measure high affinity nicotinic acetylcholine receptors, M 1 and M 2 muscarinic acetylcholine receptors, respectively. The most notable experimental result was a moderate, but significant ( P