Evidence for an irreversible interaction of bromocryptine with central dopamine receptors

Summary The effects of the dopamine agonist bromocryptine on several measures dopaminergic function were assessed in the rat. Following inhibition of impulse flow with -butyrolactone, and after dopa decarboxylase inhibition, dopa accumulation and its reversal by dopamine agonists is easily studied. In this model, bromocryptine (10 mg/kg, i.p.) caused a significant decrease in dopa accumulation in both the striatum and olfactory tubercle which was prevented, but not reversed, by the dopamine antagonist (+)-butaclamol (4 mg/mg, i.p.). The inactive isomer, (–)-butaclamol was without effect. Analysis of in vitro ³H-spiperone binding 2 h after bromocryptine (10 mg/kg, i.p.) revealed a 30% decrease in the number of striatal dopamine receptors labelled (B_max), with no change in receptor affinity for ³H-spiperone. No changes in binding were seen when animals were sacrificed 30 min or 48 h after bromocryptine. In extracellular single unit recording experiments, bromocryptine-induced depression of nigrostriatal dopamine cell firing was found to be largely reversible by the dopamine antagonist haloperidol when injected within 5 min of intravenous bromocryptine. However, when haloperidol was injected more than 20 min after bromocryptine, no reversal of bromocryptine-induced depression of cell firing was obtained. These results strongly suggest that bromocryptine interacts in an irreversible fashion with central dopaminergic receptors.