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Rewarding Effects of N-Methyl-1-(4-Methoxyphenyl)-2-Aminopropane (PMMA) in Mice: Roleof Modifications of Dopamine System Mediated through its Monoamine Oxidase Inhibition

Masahiko Funada, Naoya Aoo and Kiyoshi Wada

Background: N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA) is a structurally abbreviated congener of methamphetamine that is abused as a “designer drug”. The aim of the present study was to investigate the behavioral and neurochemical properties of PMMA in mice.

Methods: Using conditioned place preference paradigm, the rewarding effect of PMMA were examined in the ICR mice. As neurochemical study, we examined the effect of PMMA on monoamine transmission and monoamine oxidase (MAO) activity in the mouse limbic forebrain tissue (containing the nucleus accumbens).

Results: PMMA (1-30 mg/kg) produced a significant heperlocomotion and conditioned place preference. The hyper locomotion and rewarding effects of PMMA were completely suppressed by the dopamine D1 receptor antagonist SCH23390, but were not modified by the dopamine D2 receptor antagonist sulpiride or the 5-HT2 receptor antagonist ketanserin.

PMMA also significantly increased the dopamine and 3-methoxytyramine (3MT) contents in the limbic forebrain. On the other hand, the levels of the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and Homovanillic acid (HVA) were markedly reduced by PMMA in a dose-dependent manner. Monoamine oxidase (MAO) activities in the limbic forebrain were suppressed by PMMA treatment (0.04-4mM).

Conclusion: The present findings demonstrated that the dopamine D1 receptors might be involved in the expression of PMMA-induced heperlocomotion and the rewarding effects of the drug. Furthermore, the MAO-inhibitory effects of PMMA may play an important role in the PMMA-induced elevation of dopamine transmission. These behavioral and neurochemical data indicate that PMMA has a psychic dependence liability.