Evidence to Suggest that Agonist Modulation of Hyperlocomotion is Via Post-synaptic Dopamine D 2 or D 3 Receptors

Abstract

It has been suggested that a sub-population of dopamine D 3 receptors is located pre-synaptically and these serve as autoreceptors in dopamine projection areas such as the nucleus accumbens/ventral striatum. To study further the physiological role and synaptic location of the dopamine D 3 receptor, we have investigated the in vivo effect of the D 3/D 2 receptor agonist quinelorane on amphetamine-induced hyperactivity extracellular dopamine release from the nucleus accumbens of the conscious rat. Amphetamine increased dopamine release to 202 ± 34% of pre-injection control values, but quinelorane at 2.5 μg/kg, a dose which effectively blocked amphetamine-induced hyperlocomotion, had no significant effect on amphetamine-induced dopamine release. These data suggest that hyperlocomotion is mediated via post-synaptic rather than pre-synaptic dopamine receptors. Since quinelorane has significant affinity for the dopamine D 3 receptor, these effects may be via post-synaptic D 3 receptors; however, D 2 receptor effects cannot be disregarded. In summary, these data indicate that the quinelorane effect on amphetamine-stimulated hyperlocomotion is not mediated via D 3 or D 2 autoreceptors, but rather a population of receptors located post-synaptically, which appear to mediate the inhibition of rat locomotor activity. © 1997 Elsevier Science Ltd.