Behavioural interactions between 5‐hydroxytryptophan, neuroleptic agents and 5‐HT receptor antagonists in modifying rodent responding to aversive situations

Behavioural interactions between 5‐hydroxytryptophan, neuroleptic agents and 5‐HT receptor... 1 The ability of 5‐hydroxytryptophan, 5‐HT2 receptor antagonists and typical and atypical neuroleptic agents to modify behavioural responding to aversive situations was investigated in the mouse light/dark test and rat social interaction. 2 The administration of 5‐hydroxytryptophan inhibited rat social interaction and the exploratory behaviour of mice in the light/dark test. 3 The 5‐HT2 receptor antagonists, ketanserin, ritanserin, MDL11939, methysergide and RP62203, the neuroleptic agents, spiperone, haloperidol and benperidol, and the atypical neuroleptic agent, clozapine, when administered alone failed to modify mouse or rat behaviour. In contrast, when administered alone, sulpiride in rats and mice and thioridazine in rats disinhibited behaviour. 4 Methysergide, RP62203, ketanserin, ritanserin and MDL 11939 antagonized the inhibitory effects of 5‐hydroxytryptophan or reversed the inhibitory effects to one of disinhibition. 5 Low doses of spiperone (but not haloperidol or benperidol) also antagonized the inhibitory effects of 5‐hydroxytryptophan in the rat but not the mouse. Higher doses of the three neuroleptic agents caused locomotor depression in both rats and mice which obscured any specific changes in behavioural responding to the aversive situations. 6 The disinhibitory profile of sulpiride in both mice and rats and thioridazine in rats was evident during their interaction with 5‐hydroxytryptophan. Thioridazine in the mouse and clozapine in rats and mice also reversed the inhibitory effects of 5‐hydroxytryptophan to one of disinhibition. 7 In summary, we present evidence that the atypical neuroleptic agents, thioridazine and clozapine, with their known affinity for the 5‐HT2 receptors, can mimic the actions of reference 5‐HT2 receptor antagonists to antagonize the inhibitory effects of 5‐hydroxytryptophan in rodent models of anxiety. The results are intepreted in terms of drug action on different 5‐HT2 and other 5‐HT receptor subtypes. In addition, thioridazine and sulpiride have disinhibitory effects in their own right which remain to be explained. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Behavioural interactions between 5‐hydroxytryptophan, neuroleptic agents and 5‐HT receptor antagonists in modifying rodent responding to aversive situations

British Journal of Pharmacology, Volume 116 (7) – Dec 1, 1995

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Publisher
Wiley
Copyright
1995 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1111/j.1476-5381.1995.tb15954.x
Publisher site
See Article on Publisher Site

Abstract

1 The ability of 5‐hydroxytryptophan, 5‐HT2 receptor antagonists and typical and atypical neuroleptic agents to modify behavioural responding to aversive situations was investigated in the mouse light/dark test and rat social interaction. 2 The administration of 5‐hydroxytryptophan inhibited rat social interaction and the exploratory behaviour of mice in the light/dark test. 3 The 5‐HT2 receptor antagonists, ketanserin, ritanserin, MDL11939, methysergide and RP62203, the neuroleptic agents, spiperone, haloperidol and benperidol, and the atypical neuroleptic agent, clozapine, when administered alone failed to modify mouse or rat behaviour. In contrast, when administered alone, sulpiride in rats and mice and thioridazine in rats disinhibited behaviour. 4 Methysergide, RP62203, ketanserin, ritanserin and MDL 11939 antagonized the inhibitory effects of 5‐hydroxytryptophan or reversed the inhibitory effects to one of disinhibition. 5 Low doses of spiperone (but not haloperidol or benperidol) also antagonized the inhibitory effects of 5‐hydroxytryptophan in the rat but not the mouse. Higher doses of the three neuroleptic agents caused locomotor depression in both rats and mice which obscured any specific changes in behavioural responding to the aversive situations. 6 The disinhibitory profile of sulpiride in both mice and rats and thioridazine in rats was evident during their interaction with 5‐hydroxytryptophan. Thioridazine in the mouse and clozapine in rats and mice also reversed the inhibitory effects of 5‐hydroxytryptophan to one of disinhibition. 7 In summary, we present evidence that the atypical neuroleptic agents, thioridazine and clozapine, with their known affinity for the 5‐HT2 receptors, can mimic the actions of reference 5‐HT2 receptor antagonists to antagonize the inhibitory effects of 5‐hydroxytryptophan in rodent models of anxiety. The results are intepreted in terms of drug action on different 5‐HT2 and other 5‐HT receptor subtypes. In addition, thioridazine and sulpiride have disinhibitory effects in their own right which remain to be explained.

Journal

British Journal of PharmacologyWiley

Published: Dec 1, 1995

References

  • Pharmacological effects of MDL 11,939: a selective centrally acting antagonist of 5‐HT 2 receptors.
    DUDLEY, DUDLEY; WIECH, WIECH; MILLER, MILLER; CARR, CARR; CHENG, CHENG; ROEBEL, ROEBEL; DOHERTY, DOHERTY; YAMAMURA, YAMAMURA; URSIL‐LO, URSIL‐LO; PALFREYMAN, PALFREYMAN
  • Clinical studies on the mechanism of action of clozapine: the dopamine‐serotonin hypothesis of schizophrenia.
    MELTZER, MELTZER
  • 5‐Hydroxytryptamine receptors
    ZIFA, ZIFA; FILLION, FILLION

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