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REPEATED CHLORPROMAZINE ADMINISTRATION INCREASES A BEHAVIOURAL RESPONSE OF RATS TO 5‐HYDROXYTRYPTAMINE RECEPTOR STIMULATION
Author(s) -
GREEN A.R.
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb07501.x
Subject(s) - tranylcypromine , chlorpromazine , pharmacology , stimulation , agonist , tryptophan , chemistry , serotonin , endocrinology , medicine , receptor , biochemistry , monoamine oxidase , amino acid , enzyme
1 The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by l ‐tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5‐hydroxytryptamine (5‐HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and l ‐tryptophan administration 24 h after the final dose of chlorpromazine. 2 One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/ l ‐tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and l ‐tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose. 3 Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioural responses to the suggested 5‐HT agonist 5‐methoxy N,N ‐dimethyltryptamine (2 mg/kg) on day 5. 4 Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5‐hydroxytryptamine (5‐HT) concentration on day 5, but no difference in the rate of brain 5‐HT synthesis or the rate of 5‐HT accumulation after tranylcypromine and l ‐tryptophan administration. 5 There is some evidence that chlorpromazine blocks 5‐HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5‐HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5‐HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5‐HT receptors.