Nucleus accumbens opiate-dopamine interactions and locomotor activation in the rat: evidence for a pre-synaptic locus.
Locomotor activation produced by the indirect dopamine (DA) agonist amphetamine is reversed by the opiate-receptor antagonist naloxone. Since amphetamine-stimulated locomotion results from the release of DA within the nucleus accumbens (N.Acc.), it is possible that these effects of naloxone result either from a decrease in the pre-synaptic release of DA within the N.Acc. or from a disruption of the effects of DA at, or distal to, the post-synaptic DA receptor. In the present study, we investigated the effects of naloxone on the locomotor-activating properties of dopamine injected directly into the nucleus accumbens. Naloxone (0-2 mg/kg) had no significant effect of DA-stimulated locomotion; the lowest dose of naloxone tested (0.5 mg/kg) was shown to significantly disrupt the locomotor activation produced by amphetamine (0.5 mg/kg). In separate animals, very high doses of naloxone (5.0 mg/kg) had no significant effect on locomotor activation produced by the DA receptor agonist apomorphine in rats following 6-hydroxydopamine (6OHDA) denervation of the N.Acc. These results indicate that naloxone must disrupt amphetamine-stimulated locomotion through its action presynaptic to N.Acc. DA receptors.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology* / Q000502:physiology; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D006892:Hydroxydopamines; D009270:Naloxone; D016627:Oxidopamine; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine