In this study, we examined the effect of the acute p.o. administration of the
antipsychotic drug mosapramine, as well as the
antipsychotic drugs clozapine,
haloperidol and
risperidone, on the expression of Fos
protein in the medial prefrontal cortex, nucleus accumbens and dorsolateral striatum of rat brain. The administration of
mosapramine (1 or 3 mg/kg) significantly increased the number of Fos
protein positive neurons in the medial prefrontal cortex, but not in the dorsolateral striatum. In addition,
mosapramine (1, 3 or 10 mg/kg) produced a dose-dependent increase in the number of Fos
protein positive neurons in the nucleus accumbens. The acute administration of 10 mg/kg of
mosapramine significantly increased the number of Fos
protein positive neurons in all brain regions. The acute administration of
clozapine (30 mg/kg), similarly to
mosapramine at lower doses (1 or 3 mg/kg), significantly increased the number of Fos
protein positive neurons in the medial prefrontal cortex and nucleus accumbens, but not dorsolateral striatum. In contrast,
haloperidol (0.3 mg/kg) significantly increased the number of Fos
protein positive neurons in the nucleus accumbens and dorsolateral striatum, but not medial prefrontal cortex. The acute administration of
risperidone (0.3 or 1 mg/kg) did not affect the number of Fos
protein positive neurons in the medial prefrontal cortex, nucleus accumbens or dorsolateral striatum of rat brain, whereas a 3 mg/kg dose of
risperidone significantly increased the number of Fos
protein positive neurons in all brain regions. These results suggest that the ability of
mosapramine to enhance expression of Fos
protein in the medial prefrontal cortex may contribute to a
clozapine-like profile with respect to actions on negative symptoms in
schizophrenia. Furthermore, the lack of effect of low doses of
mosapramine on Fos
protein expression in the dorsolateral striatum, an area believed to play a role in movement, suggests that it may have a lower tendency to induce neurological side effects.