THE EFFECT OF COCAINE AND OTHER LOCAL-ANESTHETICS ON CENTRAL DOPAMINERGIC NEUROTRANSMISSION

The effects of cocaine on dopaminergic function in the rat were compar ed with those of other local anesthetics having an esteratic linkage ( dimethocaine, procaine) or an amide linkage (lidocaine). By means of r everse-phase HPLC with electrochemical detection and gas chromatograph y-mass spectrometry, levels of dopamine (DA) and its metabolites 3-met hoxy-tyramine (3-MT) and dihydroxyphenylacetic acid were quantified in the striatum, nucleus accumbens and prefrontal cortex after i.p. inje ction of the drugs or saline. Time course and dose response studies de termined the effects of the drugs on these parameters of dopaminergic function. These studies provide strong evidence that the three esterat ic local anesthetics cocaine, dimethocaine and procaine all increase t he synaptic presence of DA, as reflected in increased levels of 3-MT a nd the ratio of 3-MT to DA, in the striatum, nucleus accumbens and pre frontal cortex. Surprisingly, procaine had an equal or greater effect than cocaine and dimethocaine on 3-MT levels and the ratio 3-MT/DA. Th e effects of these drugs on dihydroxyphenylacetic acid, an indicator o f intraneuronal metabolism of DA, were more variable. However, the ami dergic local anesthetic lidocaine did not affect DA metabolism. Althou gh the exact mechanisms behind the dopaminergic activities of procaine and dimethocaine remain unknown, it is clear that these drugs, as wel l as cocaine, activate dopaminergic systems in the intact animal.