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Behavioural interactions between 5‐hydroxytryptophan, neuroleptic agents and 5‐HT receptor antagonists in modifying rodent responding to aversive situations
Author(s) -
Costall B.,
Naylor R.J.
Publication year - 1995
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.1476-5381.1995.tb15954.x
Subject(s) - ritanserin , thioridazine , clozapine , haloperidol , ketanserin , methysergide , spiperone , sulpiride , disinhibition , pharmacology , cyproheptadine , chlorpromazine , psychology , pimozide , 5 ht receptor , inhibitory postsynaptic potential , serotonin antagonists , 5 hydroxytryptophan , 5 ht2a receptor , serotonin , antagonist , medicine , receptor , neuroscience , schizophrenia (object oriented programming) , dopamine , psychiatry
1 The ability of 5‐hydroxytryptophan, 5‐HT 2 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‐HT 2 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‐HT 2 receptors, can mimic the actions of reference 5‐HT 2 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‐HT 2 and other 5‐HT receptor subtypes. In addition, thioridazine and sulpiride have disinhibitory effects in their own right which remain to be explained.