Prepulse inhibition of the acoustic startle response is disrupted by N-ethyl-3,4-methylenedioxyamphetamine (MDEA) in the rat.
N-Ethyl-3,4-methylenedioxyamphetamine (MDEA) is a derivative of methylenedioxyamphetamine (MDA), a substituted amphetamine with demonstrated abuse liability. MDA, MDEA and a third substituted amphetamine, methylenedioxymethamphetamine (MDMA), all produce a destructive action on central serotonin neurons and appear to induce some similar behavioral effects. The present study investigated the effects of racemic MDEA and its stereoisomers on prepulse inhibition of the acoustic startle response, a behavioral model of sensorimotor gating that is sensitive to psychostimulant drugs. Rats were subjected to 122 dB[A] acoustic noises, some of which were preceded by a weak 80 dB[A] prepulse noise. In vehicle-injected control rats, the prepulse induced a significant decrease in startle amplitude when compared to trials in which startle stimuli were not preceded by prepulses. Administration of racemic MDEA (0.3-10.0 mg/kg) and (+) MDEA (0.1-3.0 mg/kg) induced a significant attenuation in prepulse inhibition, while (-) MDEA (0.3-10.0 mg/kg) did not. Racemic MDMA (0.3-10.0 mg/kg) produced similar though not significant effects. These results confirm a stimulant-like behavioral effect of MDEA despite its relatively modest effects on dopamine markers, and support findings that the (+) stereoisomers of substituted amphetamines are more potent than tha (-) stereoisomers in producing psychostimulant-like biochemical and behavioral effects.
Department of Psychiatry, University of California, San Diego, La Jolla 92093.
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Mansbach
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Braff
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Geyer
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000161:Acoustic Stimulation; D000662:Amphetamines / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D007536:Isomerism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000187:drug effects*
D000662:Amphetamines; D015104:3,4-Methylenedioxyamphetamine; C051800:3,4-methylenedioxyethamphetamine