ArticlesAnxiolytic-Like Effects of Perospirone, a Novel Serotonin-2 and Dopamine-2 Antagonist (SDA)-Type Antipsychotic Agent
Section snippets
Subjects
The subjects were male Lister hooded rats (Nihon Dobutu, Japan), each weighing 180.5–317.5 g at the beginning of the experiments. The rats were group housed in a ventilated, temperature (23 ± 2°C)- and humidity (55 ± 10%)-controlled animal care room under a standard 12 L:12 D cycle (lights on at 0800 h, lights off at 2000 h), with free access to food and water. The housing conditions of the rats complied with the institutional guidelines of Sumitomo Pharmaceuticals Research Center.
Apparatus
The CDB test
Conditioned Defensive Burying Test
As shown in Fig. 1, there was a significant dose-related differential response to the shock and shock-control probes in animals treated with the anxiolytic diazepam [dose × probe type interaction: F(4, 90) = 3.316, p < 0.0139]. The time spent in burying the shock probe was dose dependently decreased by diazepam, F(4, 45) = 4.284, p < 0.0051, whereas that of the shock-control probe was not affected. Diazepam did not depress the motility (Fig. 2). Thus, diazepam dose dependently inhibited CDB at
Discussion
The principle findings of the present study were three fold: (a) the anxiolytic diazepam significantly inhibited CDB of the probe previously paired with the aversive stimulus (i.e., shock probe) and significantly prolonged the time spent in active SI between naive rats in the brightly illuminated, novel environment; (b) the SDA-type antipsychotic perospirone, but not the conventional antipsychotic haloperidol, mimicked the effects of diazepam by significantly inhibiting CDB at 0.3 and 1 mg/kg,
Acknowledgements
The authors thank Yoko Ueda, Hitomi Ohki, and Yasuyo Ogiu for their technical and administrative assistance.
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