Changes in 3H-spiperone, 3H-WB 4101 and 3H-dihydroalprenolol bindings to brain membranes produced by postnatal pretreatment with chlorpromazine in adult rats.
In order to elucidate possible mechanisms of the learning deficit produced by postnatal pretreatment with chlorpromazine (CPZ), changes in catecholamine receptors in the rat brain were investigated. Male neonates of Wistar strain rats were given s.c. 2 mg/kg/day of CPZ for 7 successive days from days 6 to 12 after birth. Effect of the postnatal pretreatment with CPZ on saturation constants for specific bindings of 3H-spiperone, 3H-WB 4101 and 3H-dihydroalprenolol, respectively, in 8 brain regions was investigated at 60 days after birth. Significant decreases in Bmax values of 3H-WB 4101 binding sites in the cortex, thalamus, hypothalamus, mid brain and medulla oblongata/pons and decreases in Kd values of the binding sites in thalamus, hypothalamus and mid brain were observed in CPZ-pretreated rats when compared with corresponding Bmax and Kd values obtained in saline-pretreated rats. Furthermore, significant decreases in both Bmax and Kd values of 3H-DHA binding sites in the thalamus were detected in CPZ-pretreated rats when compared with those obtained in saline-pretreated rats. However, no alterations in 3H-spiperone binding sites in all brain regions were found between CPZ- and saline-pretreated rats. These results suggest that the learning deficit observed in CPZ-pretreated rats may be produced by a functional disorder of catecholaminergic, in particular alpha 1-noradrenergic neurons in the brain.
Hayashi
T
T
Kunihara
M
M
Tadokoro
S
S
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000526:Alprenolol / Q000031:analogs & derivatives*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002090:Butyrophenones / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology*; D004082:Dihydroalprenolol / Q000378:metabolism*; D004146:Dioxanes / Q000378:metabolism*; D004147:Dioxins / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D002090:Butyrophenones; D004146:Dioxanes; D004147:Dioxins; D013134:Spiperone; D004082:Dihydroalprenolol; D000526:Alprenolol; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D002746:Chlorpromazine