Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

There is evidence that GABA-ergic as well as 5-HT-ergic neurotransmitter system are involved in the mechanism of behavioural effects of benzodiazepines. A dependence is developing during their repeated administration with behavioural signs upon withdrawal which include anxiety and increased aggressivity. We are experienced with such effects in our model of anxiety and aggression in singly-housed male mice on social dyadic interactions with non-aggressive group-housed partners. Thus, we have decided for testing of possible positive influences of serotonergics with differential 5-HT receptor subtypes occupancy on the occurrence of increased either defensive-escape behaviour (anxiety) or aggressivity in singly-housed mice during the withdrawal of repeated administration of diazepam. Selected were serotonergics reported as potential antianxiety or antiaggressive agents: the selective serotonin reuptake inhibitor fluoxetine, 5-HT1A/1B agonist eltoprazine, adrenergic-beta/5-HT1B antagonist isamoltane, 5-HT2A/2C antagonist ketanserine and D2 receptor antagonist with 5-HT influences (mainly at 5-HT3 receptors) tiapride. All these drugs administered 3 days prior to withdrawal of repeated diazepam treatment suppressed a rapid return (or even 'rebound phenomenon') to either aggressive or defensive-escape behavioural activities in singly-housed mice. The presented results bring a suggestion that the selected serotonergics might be useful in the prevention and perhaps also the treatment of behavioural signs of benzodiazepine withdrawal. (Supported by the grant No. 3426-3 from the IGA MZ ÈR.)

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Poster Number PAsulcova0517
Keywords: diazepam, dependence, withdrawal, serotonergics