COMPARATIVE BEHAVIORAL AND NEUROCHEMICAL STUDIES WITH A PSYCHOMOTOR STIMULANT, AN HALLUCINOGEN AND 3,4-METHYLENEDIOXY ANALOGS OF AMPHETAMINE

Spontaneous behaviours were assessed in freely moving rats after treat ment with equimolar doses of drugs that share a basic amphetamine stru cture. The drugs used included a psychomotor stimulant [(+)-amphetamin e (AMPH)], an hallucinogen [paramethoxyamphetamine (PMA)] and the enta ctogens 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyam phetamine (MDA) and 3,4-methylenedioxy-N-ethylamphetamine (MDE). A det ailed analysis of the frequency and duration of 30 different behaviour s and the temporal organization of the behaviours was conducted in add ition to measuring motor activity with an automated device. Levels of the biogenic amines and their acid metabolites in discrete brain regio ns and brain drug levels were also obtained. The automated motor activ ity measures discriminated among entactogens, the stimulant and the ha llucinogen, but failed to distinguish between the hallucinogen and veh icle. Principal components analysis and cluster analysis of the freque ncies and durations of the behaviours did not improve the classificati on of the drugs over the automated motor activity measures. Only the c luster analysis of the transitions between individual behaviours succe eded in differentiating the drug classes from each other and from vehi cle treatment. All the behavioural measures classified one entactogen (MDE) as an hallucinogen. Cortical 5-hydroxytryptamine (5-HT) measures grouped MDE with the other entactogens but did not distinguish AMPH f rom vehicle. However, striatal dopamine measures differentiated AMPH f rom vehicle treatment. Variations in the durations of behavioural effe cts across drugs were associated with large differences in drug levels 3 h after injection. Although the neurochemical data provided a class ification system that most closely parallels human subjective effects of these drugs, both the neurochemical and the behavioural measures su pported the existence of an entactogen class distinct from a psychomot or stimulant and an hallucinogen.