7-OH-DPAT DIFFERENTIALLY REVERSES CLOZAPINE-INDUCED AND HALOPERIDOL-INDUCED INCREASES IN FOS-LIKE IMMUNOREACTIVITY IN THE RODENT FOREBRAIN

The pattern of neurons which display haloperidol-induced Fos-like immu noreactivity closely matches the distribution of striatal D2 dopamine receptors, whereas clozapine-induced Fos-like immunoreactivity occurs primarily in regions that contain high levels of the D3 dopamine recep tor. These neuroanatomical correlations suggest that haloperidol and c lozapine may elevate Fos-like immunoreactivity by blocking D2 and D3 r eceptors respectively. In order to test this hypothesis, the abilities of prior administration of the D3 receptor-preferring agonist 7-hydro xy-N,N'-di-n-propyl-2-aminotetraline (7-OH-DPAT) to competitively reve rse haloperidol- and clozapine-induced increases in Fos-like immunorea ctivity were compared. Administration of 7-OH-DPAT (0.05 mg/kg, s.c.) 30 min before clozapine (20 mg/kg, s.c.) produced a 60% reduction in t he number of neurons that displayed clozapine-induced fos-like immunor eactivity in the major island of Calleja, nucleus accumbens and medial aspect of the striatum, while prior administration of 0.5 mg/kg (s.c. ) of 7-OH-DPAT completely reversed these increases in Fos-like immunor eactivity. In contrast, the increases in Fos-like immunoreactivity in the major island of Calleja, nucleus accumbens and striatum (medial an d dorsal aspects) induced by haloperidol (0.1 mg/kg, s.c.) were only r educed by the high dose of 7-OH-DPAT (0.5 mg/kg,s.c.). Hence, clozapin e-induced increases in Fos-like immunoreactivity were more readily rev ersed by 7-OH-DPAT than elevations in Fos-like immunoreactivity produc ed by haloperidol. These results suggest that D3 receptor blockade pla ys a larger role in mediating clozapine- than haloperidol-induced incr eases in Fos-like immunoreactivity.