Neurochemical Effects of Methylenedioxymethamphetamine in the Rat: Acute Versus Long-Term Changes

Abstract

Amphetamine-like central stimulants are one of the most well-studied classes of pharmacological agents known today. This is due to the fact that their behavioral activity is believed to be mediated primarily by the monoamines, which themselves have been scrutinized sufficiently to have earned the title “classical transmitters.” In spite of the attention given this class of agents and their relatively well-described neurochemical activities, there remains a great deal about these drugs that we do not understand. The neurotoxicity associated with high doses of many of these agents is one of these unexplained actions. Although the term high dose is used, it is important to point out that these doses are often in the range of which humans are exposed. This is particularly true in the case of 3,4-methylenedioxymethamphetamine (MDMA), as has been described elsewhere in this book. This neurotoxicity of the amphetamines is selective, in that it primarily affects the neuronal systems through which the drugs mediate their behavioral effects, i.e., the monoaminergic systems. Thus amphetamine, which is believed to cause the majority of its stimulant activities through dopamine release, causes persistent damage selectively to dopaminergic processes [1]. Methamphetamine, which is also a potent releaser of 5-HT, is neurotoxic to both the dopaminergic and serotonergic systems [2]. Finally, the selective serotonergic neurotoxicity of p-chloroamphetamine (PCA) correlates with 5-HT release as the presumed basis of most, though not all, of its behavior effects [3].