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.