Increased or decreased locomotor response in rats following repeated administration of apomorphine depends on dosage interval

Abstract

Administration of drugs that reduce the influence of dopamine at its receptor site can lead to postsynaptic supersensitivity, whereas treatment with dopamine (DA) agonists can cause postsynaptic subsensitivity. Both unaltered and enhanced postsynaptic responses to DA have been shown after pretreatment with DA agonists. In the present manuscript pretreatment with apomorphine, a dopaminergic agonist, is shown to induce either increased or reduced locomotor activity. When a drug-free period between successive injections was allowed, apomorphine induced an enhanced locomotor response, whereas a reduced response occurred when each dose was injected before the previous apomorphine dose had been completely metabolized. Pretreatment with both high (1 and 3 mg/kg) and low (0.05 mg/kg) apomorphine doses enhanced the response. Apomorphine treatment that caused enhanced locomotor responses did not modify the stereotypy response to the drug. Similar enhanced or reduced response were found in rats with partial lesions of the nigrostriatal system. These altered responses to DA agonists may have important clinical consequences. The present data also suggest the existence of a different DA systems for locomotor and stereotypy actions of dopaminergic agonists.