EVIDENCE TO SUGGEST THAT AGONIST MODULATION OF HYPERLOCOMOTION IS VIAPOSTSYNAPTIC DOPAMINE D-2 OF D-3 RECEPTORS

It has been suggested that a sub-population of dopamine D-3 receptors is located pre-synaptically and these serve as autoreceptors in dopami ne projection areas such as the nucleus accumbens/ventral striatum. To study further the physiological role and synaptic location of the dop amine D-3 receptor, we have investigated the in vivo effect of the D-3 /D-2 receptor agonist quinelorane on amphetamine-induced hyperactivity and extracellular dopamine release from the nucleus accumbens of the conscious rat. Amphetamine increased dopamine release to 202 +/- 34% o f pre-injection control values, but quinelorane at 2.5 mu g/kg, a dose which effectively blocked amphetamine-induced hyperlocomotion, had no significant effect on amphetamine-induced dopamine release. These dat a suggest that hyperlocomotion is mediated via postsynaptic rather tha n pre-synaptic dopamine receptors. Since quinelorane has significant a ffinity for the dopamine D-3 receptor, these effects may be via post-s ynaptic D-3 receptors; however, D-2 receptor effects cannot be disrega rded. In summary, these data indicate that the quinelorane effect on a mphetamine-stimulated hyperlocomotion is not mediated via D-3 or D-2 a utoreceptors, but rather a population of receptors located post-synapt ically, which appear to mediate the inhibition of rat locomotor activi ty. (C) 1997 Elsevier Science Ltd.