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Effects of the serotonin releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and fenfluramine on acoustic and tactile startle reflexes in rats.
J Pharmacol Exp Ther. 1992 Jan; 260(1):78-89.JP

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.

Authors+Show Affiliations

Marion Merrell Dow Research Institute, Cincinnati, Ohio.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1731054

Citation

Kehne, J H., et al. "Effects of the Serotonin Releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and Fenfluramine On Acoustic and Tactile Startle Reflexes in Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 260, no. 1, 1992, pp. 78-89.
Kehne JH, McCloskey TC, Taylor VL, et al. Effects of the serotonin releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and fenfluramine on acoustic and tactile startle reflexes in rats. J Pharmacol Exp Ther. 1992;260(1):78-89.
Kehne, J. H., McCloskey, T. C., Taylor, V. L., Black, C. K., Fadayel, G. M., & Schmidt, C. J. (1992). Effects of the serotonin releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and fenfluramine on acoustic and tactile startle reflexes in rats. The Journal of Pharmacology and Experimental Therapeutics, 260(1), 78-89.
Kehne JH, et al. Effects of the Serotonin Releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and Fenfluramine On Acoustic and Tactile Startle Reflexes in Rats. J Pharmacol Exp Ther. 1992;260(1):78-89. PubMed PMID: 1731054.
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TY - JOUR T1 - Effects of the serotonin releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and fenfluramine on acoustic and tactile startle reflexes in rats. AU - Kehne,J H, AU - McCloskey,T C, AU - Taylor,V L, AU - Black,C K, AU - Fadayel,G M, AU - Schmidt,C J, PY - 1992/1/1/pubmed PY - 1992/1/1/medline PY - 1992/1/1/entrez SP - 78 EP - 89 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 260 IS - 1 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/1731054/Effects_of_the_serotonin_releasers_34_methylenedioxymethamphetamine__MDMA__4_chloroamphetamine__PCA__and_fenfluramine_on_acoustic_and_tactile_startle_reflexes_in_rats_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1731054 DB - PRIME DP - Unbound Medicine ER -