The effect of cocaine and other local anesthetics on central dopaminergic neurotransmission.
The effects of cocaine on dopaminergic function in the rat were compared with those of other local anesthetics having an esteratic linkage (dimethocaine, procaine) or an amide linkage (lidocaine). By means of reverse-phase HPLC with electrochemical detection and gas chromatography-mass spectrometry, levels of dopamine (DA) and its metabolites 3-methoxytyramine (3-MT) and dihydroxyphenylacetic acid were quantified in the striatum, nucleus accumbens and prefrontal cortex after i.p. injection of the drugs or saline. Time course and dose response studies determined the effects of the drugs on these parameters of dopaminergic function. These studies provide strong evidence that the three esteratic local anesthetics cocaine, dimethocaine and procaine all increase the synaptic presence of DA, as reflected in increased levels of 3-MT and the ratio of 3-MT to DA, in the striatum, nucleus accumbens and prefrontal cortex. Surprisingly, procaine had an equal or greater effect than cocaine and dimethocaine on 3-MT levels and the ratio 3-MT/DA. The effects of these drugs on dihydroxyphenylacetic acid, an indicator of intraneuronal metabolism of DA, were more variable. However, the amidergic local anesthetic lidocaine did not affect DA metabolism. Although the exact mechanisms behind the dopaminergic activities of procaine and dimethocaine remain unknown, it is clear that these drugs, as well as cocaine, activate dopaminergic systems in the intact animal.
Graham
J H
JH
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
Maher
J R
JR
Robinson
S E
SE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D000779:Anesthetics, Local; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D003042:Cocaine; C001746:3-methoxytyramine; D004298:Dopamine