The effect of the antipsychotic drug mosapramine on the expression of Fos protein in the rat brain - Comparison with haloperidol, clozapine and risperidone

In this study, we examined the effect of the acute p.o. administration of t he antipsychotic drug mosapramine, as well as the antipsychotic drugs cloza pine, haloperidol and risperidone, on the expression of Fos protein in the medial prefrontal cortex, nucleus accumbens and dorsolateral striatum of ra t brain. The administration of mosapramine (1 or 3 mg/kg) significantly inc reased 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 prot ein positive neurons in the nucleus accumbens. The acute administration of 10 mg/kg of mosapramine significantly increased the number of Fos protein p ositive neurons in all brain regions. The acute administration of clozapine (30 mg/kg), similarly to mosapramine at lower doses (1 or 3 mg/kg), signif icantly 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 striatu m, but not medial prefrontal cortex. The acute administration of risperidon e (0.3 or 1 mg/kg) did not affect the number of Fos protein positive neuron s in the medial prefrontal cortex, nucleus accumbens or dorsolateral striat um of rat brain, whereas a 3 mg/kg dose of risperidone significantly increa sed the number of Fos protein positive neurons in all brain regions. These results suggest that the ability of mosapramine to enhance expression of Fo s protein in the medial prefrontal cortex may contribute to a clozapine-lik e profile with respect to actions on negative symptoms in schizophrenia. Fu rthermore, the lack of effect of low doses of mosapramine on Fos protein ex pression in the dorsolateral striatum, an area believed to play a role in m ovement, suggests that it may have a lower tendency to induce neurological side effects. (C) 2000 Elsevier Science Inc. All rights reserved.