Decreased adenosine cyclic 3',5'-monophosphate phosphodiesterase activity in rat straitum following chronic haloperidol treatment.
The possible involvement of cyclic nucleotide phosphodiesterase (PDE) in the supersensitivity to dopamine-receptor agonists after chronic treatment with neuroleptic drugs has been studied. Rats were given haloperidol in the drinking water for 18 days and finally injected i.p. with 10 mg/kg haloperidol. During and after this treatment the low Km form of the cyclic AMP PDE in a 10,000 g supernatant of the striata was reduced. The loss in enzyme activity was associated with a change in the chromatographic behaviour on DEAE-cellulose. The difference between control- and haloperidol-treated rats was most pronounced in the presence of 1 mM ethylene glycol-bis(aminoethylether)tetraacetic acid (EGTA) and was essentially abolished at 1 mM Ca++. This decrease in cyclic AMP PDE may explain some of the supersensitivity to dopamine-receptor agonists observed following chronic neuroleptic treatment.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D002848:Chromatography, DEAE-Cellulose; D003342:Corpus Striatum / Q000201:enzymology*; D004533:Egtazic Acid / Q000494:pharmacology; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D013997:Time Factors
D011954:Receptors, Dopamine; D004533:Egtazic Acid; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006220:Haloperidol