Atypical Antipsychotic Drugs Selectively Increase Neurotensin Efflux in Dopamine Terminal Regions

Typical antipsychotic drugs, such as haloperidol and chlorpromazine, increase synthesis of the neuropeptide neurotensin (NT) in both the striatum and the nucleus accumbens, whereas atypical antipsychotic drugs, such as clozapine and olanzapine, do so only in the nucleus accumbens. By using in vivo m...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-09, Vol.95 (19), p.11462-11464
Main Authors: Radke, James M., Owens, Michael J., Ritchie, James C., Nemeroff, Charles B.
Format: Article
Language:English
Subjects:
Animals
Antipsychotic agents
Antipsychotic Agents - pharmacology
Benzodiazepines
Biological Sciences
Caudate nucleus
Cerebrospinal fluid
Clozapine - pharmacology
Corpus Striatum - drug effects
Extracellular fluid
Haloperidol - pharmacology
Infusion Pumps
Injections
Male
Medication administration
Messenger RNA
Microdialysis
Neurons
Neurotensin - metabolism
Nucleus accumbens
Nucleus Accumbens - drug effects
Olanzapine
Pirenzepine - analogs & derivatives
Pirenzepine - pharmacology
Rats
Rats, Sprague-Dawley
RNA, Messenger - drug effects
Vehicles
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Summary:Typical antipsychotic drugs, such as haloperidol and chlorpromazine, increase synthesis of the neuropeptide neurotensin (NT) in both the striatum and the nucleus accumbens, whereas atypical antipsychotic drugs, such as clozapine and olanzapine, do so only in the nucleus accumbens. By using in vivo microdialysis, we now report that acute administration of haloperidol, clozapine, or olanzapine failed to alter the release of NT in either the striatum or nucleus accumbens. In contrast, chronic administration of haloperidol for 21 days increased NT release in both the striatum and nucleus accumbens, whereas treatment for 21 days with the atypical antipsychotic drugs, clozapine or olanzapine, increased NT release selectively in the nucleus accumbens. These findings suggest that (i) increased NT mRNA expression and NT tissue concentrations are associated with increases in the extracellular fluid concentrations of the peptide and (ii) atypical antipsychotic drugs may exert their therapeutic effects and produce fewer side effects by virtue of their selectivity in limbic compared with striatal, target neurons.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.19.11462