In vivo microdialysis evidence for transient dopamine release by benzazepines in rat striatum

The effects of benzazepine derivatives on extracellular levels of dopamine (DA) and L-3,4-dihydroxy-phenylacetic acid (DOPAC) in the dorsal striatum of freely moving rats were studied using in vivo microdialysis. Direct injection of SKF-38393 (0.5 or 1.5 micrograms/0.5 microliter), a selective D1 receptor agonist, into the striatum through a cannula secured alongside a microdialysis probe produced a rapid dose-dependent transient increase in striatal DA efflux and a more gradual reduction in efflux of DOPAC. The rapid increase in DA efflux was not affected by infusion of tetrodotoxin (TTX; 2 microM) or Ca(2+)-free Ringer's solution and occurred after either enantiomer of SKF-38393. A TTX-insensitive increase in DA level similar to that induced by SKF-38393 was also seen after other benzazepines acting as agonists (SKF-75670 and SKF-82958, each 1.5 micrograms in 0.5 microliter) and antagonists (SCH-23390, 1.5 micrograms in 0.5 microliter) at the D1 receptor and after (+)-amphetamine. These effects were inhibited by infusion of nomifensine (100 microM). It is concluded that the transient increases in striatal DA efflux seen after intrastriatal injection of SKF-38393 and other benzazepines are not mediated by presynaptic D1 receptors but by an amphetamine-like action on the dopamine transporter.