Striatal homogenates from animals chronically treated with haloperidol stimulate dopamine and GABA uptake in cultures of rostral mesencephalic tegmentum.
The effect of pharmacologic denervation of striatal tissue on the production of growth promoting factors was examined in a cell culture system. Relative to saline-treated controls, rats were rendered behaviorally hypersensitive to a subsequent apomorphine challenge by 2 months of chronic treatment with haloperidol. Four days following chronic treatment, the animals were killed and the striata and cerebella were homogenized in Hank's Balanced Salt solution. The supernatants of these crude homogenates were then added to E-13 rostral mesencephalic tegmentum cultures for 6 days. Within 24 h, the haloperidol-treated striatal supernatants induced an overt increase in culture growth relative to all other supernatants. After 6 days, cultures incubated with haloperidol-treated striatal supernatants exhibited a significant increase in dopamine and GABA uptake relative to cultures incubated with all other supernatants. This effect was observed in the presence and absence of glia. The relative degree of this increased uptake was dependent upon the amount of haloperidol-treated striatal supernatant added. Boiling the supernatant removed the growth promoting effect. These results suggest that pharmacologic denervation of striatal tissue leads to a "target-specific" increase in growth promoting activity that may play a role in the pharmacologic and behavioral effects of haloperidol.
Carvey
P M
PM
Department of Neurological Sciences, Rush-Presbyterian St. Lukes Medical Center, Chicago, Illinois.
Ptak
L R
LR
Kao
L
L
Klawans
H L
HL
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003714:Denervation; D004298:Dopamine / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects; D013681:Tegmentum Mesencephali / Q000166:cytology* / Q000254:growth & development; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics* / Q000494:pharmacology
D005680:gamma-Aminobutyric Acid; D006220:Haloperidol; D004298:Dopamine