The role of dopaminergic mechanisms in naloxone-induced inhibition of apomorphine-induced stereotyped behavior

Abstract

Although a number of reports has recently suggested naloxone (NX) might affect dopamine (DA) agonist-elicited behavior, the effect of NX on apomorphine-induced sterotyped behavior (AISB) has not yet been systematically investigated. Doses of NX varying from 0.20 to 20.0 mg/kg were administered prior to the injection of apomorphine (0.5 mg/kg), a directly acting DA agonist, and the effect of NX on AISB was subsequently assessed. A sequential doubling of the dose of NX administered from 0.20 to 3.20 mg/kg generated a partial antagonist curve for AISB which fell in a linear manner from 0.20 to 0.40 mg/kg NX and thereafter became essentially asymptotic with 20 mg/kg producing the same effect on AISB as 0.4 mg/kg. Pretreatment with 0.4 mg/kg NX produced a sigmoidal inhibition of the stereotypy induced by successive doses of apomorphine (0.10–0.25 mg/kg). In a subsequent study, a low dose of NX (0.05 mg/kg) was combined with the specific DA receptor antagonist haloperidol (0.01 or 0.05 mg/kg) to determine if extremely low doses of the two antagonists could act synergistically. This was subsequently confirmed. Moreover, while a low dose of haloperidol (0.20 mg/kg) completely abolished AISB, 100 × this dose of NX (20.0 mg/kg) was only partially effective in this respect, indicating that NX, unlike haloperidol, exerts a partial antagonist effect relative to AISB. Furthermore, the marked synergistic effect of the very low doses of NX and haloperidol on blocking AISB was greater than their additive postsynaptic effects, suggesting that the effect of NX on AISB may in part be presynaptic.