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The production of asymmetry and circling behaviour following unilateral, intrastriatal administration of neuroleptic agents: a comparison of abilities to antagonise striatal function.

Abstract：

:The abilities of typical and atypical neuroleptic agents to antagonise at striatal dopamine receptors were determined in the rat. Neuroleptic agents were injected unilaterally into the striatum and asymmetric body posturing/circling behaviour (always ipsilateral to the side of neuroleptic injection) assessed (1) to neuroleptic challenge alone (vehicle injected into the contralateral striatum), (2) as that revealed after neuroleptic challenge by peripherally administered apomorphine or (3) by dopamine injection into the contralateral striatum. Unilateral intrastriatal fluphenazine (1-5 micrograms), cis- and trans-flupenthixol (1-20 micrograms), haloperidol (0.5-5 micrograms), thioridazine (5-10 micrograms), clozapine (1-5 micrograms), tiapride (1-5 micrograms), metoclopramide (1-10 micrograms), (+)-sulpiride (20 micrograms) and piperoxan (10 micrograms) each failed, alone, to cause any postural asymmetry/circling. However, ipsilateral asymmetry was induced by unilateral intrastriatal (-)-sulpiride (1-5 micrograms). In contrast, ipsilateral asymmetry developed when the intrastriatal injection of all neuroleptic agents (excepting (+)-sulpiride and trans-flupenthixol) was followed by peripheral challenge with apomorphine: effective neuroleptic doses were all in the range 0.5-10 micrograms, although (-)-sulpiride was effective at 0.001-0.1 microgram. Active circling was only recorded for (-)-sulpiride and tiapride. The striatal imbalance caused by (-)-sulpiride could be revealed by apomorphine for 24 h, although other intrastriatal neuroleptic responses persisted for 6-8 h. The abilities of all neuroleptic agents to cause striatal imbalance could also be revealed by injecting dopamine into the contralateral striatum (at a dose which alone did not cause any asymmetric motor responding). These intrastriatal injection approaches are forwarded as valuable techniques for determining striatal dopamine antagonist activity in the rodent.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Costall B,Kelly ME,Naylor RJ

doi

10.1016/0014-2999(83)90531-9

subject

Has Abstract

pub_date

1983-12-09 00:00:00

pages

79-86

issue

1-2

eissn

0014-2999

issn

1879-0712

pii

0014-2999(83)90531-9

journal_volume

pub_type

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The production of asymmetry and circling behaviour following unilateral, intrastriatal administration of neuroleptic agents: a comparison of abilities to antagonise striatal function.