7-OH-DPAT differentially reverses clozapine- and haloperidol-induced increases in Fos-like immunoreactivity in the rodent forebrain.
The pattern of neurons which display haloperidol-induced Fos-like immunoreactivity 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 receptor. These neuroanatomical correlations suggest that haloperidol and clozapine may elevate Fos-like immunoreactivity by blocking D2 and D3 receptors respectively. In order to test this hypothesis, the abilities of prior administration of the D3 receptor-preferring agonist 7-hydroxy-N,N'-di-n-propyl-2-aminotetraline (7-OH-DPAT) to competitively reverse haloperidol- and clozapine-induced increases in Fos-like immunoreactivity 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 the number of neurons that displayed clozapine-induced Fos-like immunoreactivity 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 immunoreactivity. In contrast, the increases in Fos-like immunoreactivity in the major island of Calleja, nucleus accumbens and striatum (medial and dorsal aspects) induced by haloperidol (0.1 mg/kg, s.c.) were only reduced by the high dose of 7-OH-DPAT (0.5 mg/kg, s.c.). Hence, clozapine-induced increases in Fos-like immunoreactivity were more readily reversed by 7-OH-DPAT than elevations in Fos-like immunoreactivity produced by haloperidol. These results suggest that D3 receptor blockade plays a larger role in mediating clozapine- than haloperidol-induced increases in Fos-like immunoreactivity.
Vahid-Ansari
F
F
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Robertson
G S
GS
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D006220:Haloperidol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D016548:Prosencephalon / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D016760:Proto-Oncogene Proteins c-fos; D013764:Tetrahydronaphthalenes; D003024:Clozapine; D006220:Haloperidol; C031349:7-hydroxy-2-N,N-dipropylaminotetralin