Abstract |
Previous studies have revealed that 5-HT(1A) agonists ameliorate antipsychotic-induced extrapyramidal symptoms (EPS) through postsynaptic 5-HT(1A) receptors. Here, we conducted an intracerebral microinjection study of (+/-)-8-hydroxy-2-(di-n-propylamino)- tetralin ((+/-)8- OH-DPAT) to determine the action site of the 5-HT(1A) agonist in alleviating EPS. Bilateral microinjection of(+/-)8- OH-DPAT (5 microg/1microL per side) either into the primary motor cortex (MC) or the dorsolateral striatum (dlST) significantly attenuated haloperidol-induced catalepsy in rats. The anticataleptic action of (+/-)8- OH-DPAT was more prominent with the MC injection than with the dlST injection. WAY-100135 (a selective 5-HT(1A) antagonist) completely antagonized the reversal of haloperidol-induced catalepsy both by intracortical and intrastriatal (+/-)8- OH-DPAT. Furthermore, lesioning of dopamine neurons with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg/day, i.p., for 4 days) did not alter the anti-EPS actions of (+/-)8- OH-DPAT in a mouse pole test. The present results strongly suggest that 5-HT(1A) agonist alleviates antipsychotic-induced EPS by activating postsynaptic 5-HT(1A) receptors in the MC and dlST, probably through non-dopaminergic mechanisms.
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Authors | Saki Shimizu, Ayaka Tatara, Junta Imaki, Yukihiro Ohno |
Journal | Progress in neuro-psychopharmacology & biological psychiatry
(Prog Neuropsychopharmacol Biol Psychiatry)
Vol. 34
Issue 6
Pg. 877-81
(Aug 16 2010)
ISSN: 1878-4216 [Electronic] England |
PMID | 20398719
(Publication Type: Journal Article)
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Copyright | Copyright (c) 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Antipsychotic Agents
- Hydroxydopamines
- Piperazines
- Serotonin Antagonists
- Receptor, Serotonin, 5-HT1A
- WAY 100135
- Haloperidol
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Topics |
- Animals
- Antipsychotic Agents
(pharmacology)
- Basal Ganglia Diseases
(chemically induced, metabolism)
- Corpus Striatum
(drug effects, metabolism)
- Haloperidol
(pharmacology)
- Hydroxydopamines
(pharmacology)
- Male
- Microinjections
- Motor Cortex
(drug effects, metabolism)
- Neurons
(drug effects, metabolism)
- Piperazines
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Serotonin, 5-HT1A
(metabolism)
- Serotonin Antagonists
(pharmacology)
- Statistics, Nonparametric
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