Effect of inhibiting enkephalin catabolism in the VTA on motor activity and extracellular dopamine.
The mixed inhibitor of enkephalin catabolism, kelatorphan, was microinjected into the ventral tegmental area (VTA) of rats to determine if endogenous enkephalins can modulate dopamine transmission in the mesoaccumbens projection. The concentration of extracellular dopamine content in the nucleus accumbens was monitored using in vivo microdialysis simultaneously with measuring motor behavior. Kelatorphan microinjection into the VTA produced a dose-related increase in motor activity and extracellular dopamine in the nucleus accumbens. While the change in extracellular dopamine was modest as compared to exogenous stimulation by a mu agonist such as DAMGO, there was a marked increase in the extracellular content of dopamine and serotonin metabolites. This suggests that mesoaccumbens dopamine transmission is under tonic control of endogenous enkephalins at the ventral tegmental area level.
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Département de Pharmacochimie Moléculaire et Structurale, U266 INSERM, URA D1500 CNRS, Faculté de Pharmacie, Paris, France.
Kalivas
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Duffy
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Roques
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D000595:Amino Acid Sequence; D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D008297:Male; D008845:Microinjections; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000378:metabolism
D004151:Dipeptides; D004745:Enkephalins; C042591:kelatorphan; D004298:Dopamine