Decreased responsiveness to low doses of apomorphine after dopamine agonists and the possible involvement of hyposensitivity of dopamine 'autoreceptors'.

Apomorphine in low dosage (0.3 mg/kg) inhibits climbing behavior, a stereotyped motor activity, in mice. Pretreatment with apomorphine in low doses (0.125 or 0.25 mg/kg) or with piribedil (25 mg/kg), a weak dopamine agonist, results in a less marked inhibitory effect of the test dose of apomorphine. Apomorphine in low dosage or piribedil are also able to antagonize the increase in striatal homovanillic acid elicited by treatment with gammabutyrolactone. Thus, low stimulation of dopamine receptors can regulate the synthesis and release of dopamine even in the absence of impulse flow in dopaminergic neurons, and the initial stimulation of the receptors mediating such effects may lead to a state of hyposensitivity to further stimulation. The hypothesis that such receptors are autoreceptors is discussed.