Anxiolytic activity of E-5842, a potential atypical antipsychotic, in the isolation-induced ultrasonic vocalizations of rat pups
X. Codony, A. Fisas, M. Jané, A.J. Farré and X. Guitart
Central Nervous System, Laboratorios Dr. Esteve, S.A., Barcelona, Spain
Rationale
Ultrasonic vocalization (USV) in rat pups is a well-accepted model with which to identify anxiolytic drugs, representing a measure that is relatively independent of additional behavioral and physiological variables. Anxiolytic drugs, such as benzodiazepine receptor agonists or 5-HT1A agonists, are active in this model - but so too are the mixed antidepressant/anxiolytic drugs, including the selective serotonin re-uptake inhibitors, fluoxetine and paroxetine. The potential atypical antipsychotic E-5842 has been shown to possess anxiolytic properties in different animal models. The present study was undertaken to compare the activity of E-5842 to that of several typical and atypical antipsychotics, using diazepam as a reference compound.
Methods
Each rat pup (~14 days old, either male or female) was separated from the dam. Its body temperature was taken and negative geotaxis evaluated. The pup was then isolated in a glass tube, and the number of USVs it produced were recorded using the UltraVox software system.
Results
As expected, diazepam reduced USV. E-5842 also reduced USV at concentrations of 1.5, 3.0 and 0.6 mg/kg. The antipsychotics, haloperidol and clozapine, did not reduce USV, but olanzapine, risperidone and chlorpromazine did. These results do not allow us to distinguish the typical from the atypical antipsychotics, though the anxiolytic-like activity has been postulated to be a distinction between them. Their effects on body temperature and negative geotaxis will also be reported, reflecting no relationship between them and USV.
Conclusions
E-5842 is active in the USV model of anxiety, reducing the number of calls in a dose-dependent manner. Its effects on USV do not seem to be related to changes in body temperature or motor impairment. These data may support the idea that the USV-reducing effect is a specific property of drugs with anxiolytic capabilities, highlighting the anxiolytic-like properties of E-5842.
Paper presented at Measuring Behavior 2002 , 4th International Conference on Methods and Techniques in Behavioral Research, 27-30 August 2002, Amsterdam, The Netherlands