Sub-chronic administration of (?)-3-PPP and central dopamine receptor sensitivity changes

Abstract

The effects of sub-chronic treatment with (−)-3-PPP (8 mg/kg, s.c., b.i.d. for 21 days), a dopaminergic agent with mixed agonist/antagonist properties, were investigated by means of behavioural andin vivo biochemical methods. There was no change in basal locomotor activity and central dopamine (DA) synthesis after 24 hours withdrawal. A slight, though significant reduction of the locomotor suppressive effect and of the DA synthesis-stimulating effect of acute (−)-3-PPP challenge doses of 0.125 and 1.0 mg/kg (s.c.), respectively, were demonstrated in (−)-3-PPP-pretreated as compared to vehicle-pretreated rats. No change in either action was evident after acute challenge with 8.0 mg/kg (s.c.) of the drug. The plasma levels of (−)-3-PPP were virtually unchanged by pretreatment with active drug. The findings are discussed in terms of a modest down- and up-regulation of DA autoreceptors and postsynaptic receptors, respectively, induced by the subchronic (−)-3-PPP treatment.