Effects of the serotonin releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and fenfluramine on acoustic and tactile startle reflexes in rats.
J H Kehne, T C McCloskey, Vicki L. Taylor, Christine K. Black, Gina M. Fadayel, C J Schmidt
Journal of Pharmacology and Experimental Therapeutics 1992 DOI: 10.1016/s0022-3565(25)11255-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 4-chloroamphetamine (PCA) 3 4-methylenedioxymethamphetamine (MDMA) fenfluramine (FEN) MDL 27 777A fluoxetine haloperidol d-amphetamine 5 7-dihydroxytryptamine |
| Dose | 20 mg/kg of MDMA |
| Duration | 3.5-hr test session |
| Topics | Serotonin MDMA |
| Keywords | Animals Rats, inbred strains P-chloroamphetamine Fenfluramine Fluoxetine 5,7-dihydroxytryptamine Indenes N-methylaspartate Reflex, acoustic Touch Dose-response relationship, drug Male Reflex, startle |
| Key findings | PCA and MDMA produced similar prolonged, dose-related excitation of acoustic and tactile startle reflexes that was mediated by central serotonin pathways, including ascending dorsal raphe and descending spinal projections, whereas fenfluramine did not excite startle and tended to depress acoustic startle. The authors suggest differences in neurochemical properties or patterns of serotonin release may underlie these distinct behavioral profiles. |
Abstract
The substituted amphetamines 4-chloroamphetamine (PCA), 3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine (FEN) share the common neurochemical action of acutely releasing central serotonin (5-HT), and yet their behavioral effects are quite different. The present study evaluated the effects of these compounds on acoustic and tactile startle reflexes. PCA and MDMA were qualitatively similar in producing dose-related increases in acoustic and tactile startle reflexes that were slow in onset, but sustained throughout the 3.5-hr test session. Changes in motor activity did not account for the observed excitation of startle. In marked contrast to MDMA and PCA, FEN did not alter tactile startle and tended to depress acoustic startle. The excitatory effect of 20 mg/kg of MDMA was prevented by the 5-HT uptake blockers MDL 27,777A and fluoxetine. MDMA excitation was not affected by a dose of the dopamine antagonist haloperidol that attenuated the startle-enhancing effect of d-amphetamine. MDMA excitation was greatly attenuated by a general depletion of central 5-HT produced by prior intraventricular injection of the 5-HT neurotoxin 5,7-dihydroxytryptamine. PCA and MDMA excitations of startle were attenuated in rats specifically depleted of spinal 5-HT or in rats with radio frequency lesions of the dorsal raphe nucleus. Thus, PCA and MDMA have similar prolonged excitatory effects on startle reflexes that are mediated by ascending (dorsal raphe) and descending (spinal) pathways, whereas FEN differs in its lack of excitation of startle. Differences in the neurochemical properties of these compounds or their patterns of 5-HT release may underlie their different behavioral profiles.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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