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INCREASED CENTRAL 5‐HYDROXTRYPTAMINE RECEPTOR MECHANISMS IN RATS AFTER CHRONIC NEUROLEPTIC TREATMENT
Author(s) -
DAWBARN D.,
LONG S.K.,
PYCOCK C.J.
Publication year - 1981
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.1476-5381.1981.tb16784.x
Subject(s) - quipazine , striatum , trifluoperazine , agonist , medicine , fenfluramine , endocrinology , 5 ht receptor , serotonin , dopamine , pharmacology , chemistry , receptor , calmodulin , calcium
1 The behavioural responses of drugs known to act through central 5‐hydroxytryptamine (5‐HT) mechanisms have been investigated in rats receiving a neuroleptic (trifluoperazine) in their drinking water for 4 to 6 months. 2 5‐Hydroxytryptophan (5‐HTP) induced 5‐HT‐dependent behaviours including head bobbing and lateral head weaving, reciprocal forepaw treading, tremor, backward walking, body writhing and ‘wet‐dog’ shakes. In doses of 50 to 150 mg/kg, 5‐HTP induced more intense behavioural effects in neuroleptic‐treated rats than in the control animals. 3 Similarly the putative 5‐HT agonist, quipazine (1 to 20 mg/kg) and the 5‐HT releasing drug, fenfluramine (5 to 20 mg/kg), both induced significantly greater motor responses in the chronically neuroleptic‐treated rats. 4 A 5‐HT uptake inhibitor (femoxetine, 2.5 to 10 mg/kg) had little behavioural effect in either control or trifluoperazine‐treated rats. 5 Total specific high‐affinity binding of radiolabeled 5‐HT was significantly increased in crude membrane fractions prepared from the cortex, striatum and substantia nigra of neuroleptic‐treated rats compared to control animals. 6 High‐affinity uptake of radiolabeled 5‐HT into striatal slices was similar in experimental and control animals. 7 Behavioural and biochemical data would indicate that postsynaptic 5‐HT mechanisms are enhanced in rats treated chronically with trifluoperazine. Chronic neuroleptic therapy may thereby induce cerebral 5‐HT receptor supersensitivity in addition to the well‐documented cerebral dopamine receptor supersensitivity.