ACTIVATION OF POSTSYNAPTIC STRIATAL DOPAMINE-RECEPTORS, MONITORED BY EFFLUX OF CAMP INVIVO

Intracerebral dialysis was used to monitor the change of extracellular concentration of striatal cAMP in rats anaesthetised with chloral hydrate. Forskolin (1-10 μM), an activator of adenylate cyclase, caused a concentration-dependent increase in efflux of cAMP, which was decreased by (+)PHNO (10 μM), an effect probably mediated by D2 sites, since (-)-sulpiride, a D2 receptor antagonist prevented these effects. Dopamine (1-100 μM) also increased the efflux of cAMP but only when the activity of monoamine oxidase and reuptake of dopamine were concomitantly blocked. The D1 receptor agonist SKF 38393 (1-100 μM) caused a concentration-dependent increase in efflux of cAMP, which was blocked by the D1 receptor antagonist SCH 23390 (1-100 μM), but was unaffected by the D2 receptor antagonist sulpiride (10 μM) or by depletion of the concentration of striatal dopamine after pretreatment with 6-hydroxydopamine. Taken together, these results indicate that intracerebral dialysis may be used to monitor the interaction of drugs with post-synaptic dopamine receptors in vivo. © 1990.