Effects of cocaine on methamphetamine-induced neurochemical changes: characterization of cocaine as a monoamine uptake blocker.

Many of the rewarding aspects of cocaine are thought to be due to the ability of this stimulant to block reuptake of monoamines. However, because of its ability also to cause transmitter release, it is difficult to examine the properties of cocaine as an uptake blocker using in vitro techniques such as tissue slices or synaptosomes. Thus, we have evaluated cocaine as a blocker of dopamine and 5-hydroxytryptamine uptake processes by determining the in vivo effect of concurrent administrations of cocaine on the neurochemical effects of methamphetamine treatments. These findings demonstrated that cocaine like 5-hydroxytryptamine uptake blockers such as citalopram, greatly attenuated or blocked decreases in striatal and cortical tryptophan hydroxylase activities and concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid induced by multiple and single methamphetamine administrations. In contrast to other dopamine uptake blockers, such as amfonelic acid, cocaine did not attenuate the methamphetamine effects on striatal tyrosine hydroxylase activity and the concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid. The neurochemical findings were correlated with behavioral analyses.