The effect of clozapine on Fos protein immunoreactivity in the rat forebrain is not mimicked by the addition of α1-adrenergic or 5HTZ receptor blockade to haloperidol

The involvement of α1-adrenergic and 5HT2-receptor blockade in the induction of Fos protein produced by the ‘atypical’ neuroleptic clozapine was investigated in the rat forebrain. The Fos protein immunohistochemical technique has been used to identify the anatomical substrate underlying the effects of typical and atypical neuroleptics. Clozapine (20 mg/kg) induced a significantly higher Fos protein immunoreactivity response in the medial prefrontal cortex and a significantly lower response in the dorsolateral striatum compared to the effect of haloperidol (1 mg/kg). The a,-adrenergic antagonist prazosin (0.3 and 1.0 mg/kg) and the 5HT2 antagonist ritanserin (1 and 3 mg/kg) did not increase Fos protein immunoreactivity by themselves and did not mimic the clozapine response when co-administered with haloperidol (1 mg/kg). Consequently, this study suggests that neither α1-adrenergic receptor blockade nor the 5HT2-receptor blockade accounts for the unique Fos protein expression pattern produced by clozapine.