Evidence to suggest that agonist modulation of hyperlocomotion is via post-synaptic dopamine D2 or D3 receptors.
It has been suggested that a sub-population of dopamine D3 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 D3 receptor, we have investigated the in vivo effect of the D3/D2 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% of pre-injection control values, but quinelorane at 2.5 micrograms/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 D3 receptor, these effects may be via post-synaptic D3 receptors; however, D2 receptor effects cannot be disregarded. In summary, these data indicate that the quinelorane effect on amphetamine-stimulated hyperlocomotion is not mediated via D3 or D2 autoreceptors, but rather a population of receptors located post-synaptically, which appear to mediate the inhibition of rat locomotor activity.
Thorn
L
L
SmithKline Beecham, Harlow, U.K. Lynn_Thorn-1@sbphrd.com
Ashmeade
T E
TE
Storey
V J
VJ
Routledge
C
C
Reavill
C
C
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000187:drug effects; D050637:Receptors, Dopamine D3
D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D011804:Quinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000661:Amphetamine; D004298:Dopamine; C047726:quinelorane