RÉSUMÉ
Dextromethorphan, a noncompetitive blocker of the N-methyl-D-aspartate (NMDA) type of glutamate receptor, at 45, 60 and 75 mg/kg, ip doses induced a behavioural syndrome characterised by reciprocal forepaw treading, lateral head-weaving, hind-limb abduction and flat body posture. Such type of behavioural syndrome is induced by 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH-DPAT) by directly stimulating the central postsynaptic 5-hydroxytryptamine (5-HT, serotonin) receptors of the 5-HT1A type. Pretreatment with buspirone (5, 10 mg/kg, ip) and l-propranolol (10, 20 mg/kg, ip) antagonised the behavioural syndrome induced by 8-OH-DPAT and dextromethorphan. Pretreatment with p-chlorophenylalanine (100 mg/kg/day x 4 days) antagonised the behavioural syndrome induced by dextromethorphan and dexfenfluramine but had no significant effect on 8-OH-DPAT induced behavioural syndrome. This indicates that dextromethorphan induces the behavioural syndrome by releasing 5-HT from serotonergic neurons with resultant activation of the postsynaptic 5-HT1A receptors by the released 5-HT. Pretreatment with fluoxetine (10 mg/kg, ip) significantly potentiated the behavioural syndrome induced by dextromethorphan and 5-hydroxytryptophan but significantly antagonised dexfenfluramine induced behavioural syndrome. This indicates that dextromethorphan releases 5-HT by a mechanism which differs from that of dexfenfluramine. Dextromethorphan may be releasing 5-HT by blocking the NMDA receptors and thereby counteracting the inhibitory influence of l-glutamate on 5-HT release.
Sujet(s)
7-Dipropylamino-5,6,7,8-tétrahydro-1-naphtol/toxicité , Animaux , Antitussifs/toxicité , Comportement animal/effets des médicaments et des substances chimiques , Buspirone/pharmacologie , Système nerveux central/effets des médicaments et des substances chimiques , Dexfenfluramine/toxicité , Dextrométhorphane/toxicité , Fluoxétine/pharmacologie , Mâle , Propranolol/pharmacologie , Rats , Rat Wistar , Sérotonine/physiologie , Agonistes des récepteurs de la sérotonine/toxicité , SyndromeRÉSUMÉ
Isatin (2,3-dioxoindole), one of the components of tribulin, which has been postulated to function as an endogenous marker of stress and anxiety, was shown to induce a dose-related attenuation of learning acquisition in an active avoidance test and inhibition of learning retention, or memory, in a step-down passive avoidance paradigm and transfer latency in an elevated plus-maze, in rats. Earlier studies have indicated that isatin functions as a 5-hydroxytryptamine (5-HT)3 receptor agonist in its anxiogenic activity in rats and is an antagonist at mammalian atrial natriuretic peptide (ANP) receptors. Since 5-HT3 receptor antagonists and centrally administered ANP have been shown to facilitate learning and memory, the observed memory dysfunction induced by isatin can be attributed to its receptor activity at 5-HT3 and ANP receptors. The investigation also indicates that anxiogenic agents are likely to disrupt memory functions.