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.
Tomiyama
K
K
Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan.
Koshikawa
N
N
Funada
K
K
Oka
K
K
Kobayashi
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007267:Injections; D008297:Male; D017551:Microdialysis; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013779:Tetrodotoxin / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D013779:Tetrodotoxin; D000661:Amphetamine; D004298:Dopamine