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ABSTRACT The locomotor hyperactivity induced by 3,4-methylenedioxymethamphetamine (MDMA) and related drugs in rats appears to be due to the drug-induced release of presynaptic serotonin

(5-HT). Thus, these drugs increase locomotor activity by acting as indirect 5-HT agonists. The subtype of 5-HT receptor upon which this released 5-HT acts postsynaptically to produce the

activating effect of MDMA-like drugs is not known. When tested under conditions in which MDMA increases locomotion, direct agonists at both 5-HT1A and 5-HT1C12 receptors consistently

decrease locomotion. Hence, the present experiments tested the hypothesis that the hyperactivity produced by the release of endogenous 5-HT is due to the activation of 5-HT1B receptors.

Using the Behavioral Pattern Monitor (BPM), the profile of behavioral effects of a 5-HT1B agonist, 5-methoxy-3(1,2,3,6)tetrahydropyridin- 4yl)-1H-indole (RU 24969), was compared to that

previously described for MDMA and related indirect 5-HT agonists. The BPM provided detailed information regarding the amount and qualitative patterning of locomotor activity and

investigatory responses in rats. Various doses of RU 24969 (1.25 to 5 mg/kg) were administered to naive male rats 10 minutes prior to placement in the test chambers. As previously reported

for MDMA, locomotor activity increased with dose, and investigatory rearings and holepokes decreased. The hyperactivity was characterized by repetitive spatial patterns of locomotion that

were qualitatively similar to those produced by indirect 5-HT agonists such as MDMA and dissimilar to those produced by indirect dopamine (DA) agonists such as amphetamine. Pretreatment with

racemic propranolol but not (+)propranolol antagonized the hyperactivity induced by RU 24959. Fluoxetine, a 5-HT reuptake inhibitor, failed to block the locomotor activating effects of RU

24969. These findings confirm the similarity between the behavioral effects of RU 24969 and indirect 5-HT agonists and suggest that the locomotor hyperactivity produced by both RU 24969 and

MDMA is mediated by the activation of 5-HT1B receptors. Although the effects of MDMA on 5-HT1B receptors are secondary to its ability to release presynaptic 5-HT, the activation produced by

RU 24969 appears to be a consequence of its direct agonist effects. SIMILAR CONTENT BEING VIEWED BY OTHERS EFFECTS OF ACUTE AND CHRONIC ADMINISTRATION OF TRACE AMINE-ASSOCIATED RECEPTOR 1

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Article Open access 19 September 2024 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * From the Department of Psychiatry, School of Medicine, University of California, San Diego, La

Jolla, California Nancy L. Rempel B.A., Clifton W. Callaway Ph.D. & Mark A. Geyer Ph.D. Authors * Nancy L. Rempel B.A. View author publications You can also search for this author

inPubMed Google Scholar * Clifton W. Callaway Ph.D. View author publications You can also search for this author inPubMed Google Scholar * Mark A. Geyer Ph.D. View author publications You

can also search for this author inPubMed Google Scholar ADDITIONAL INFORMATION Address reprint requests to: Mark A. Geyer, Ph.D., Department of Psychiatry, 0804, University of California,

San Diego, La Jolla, California 92093-0804. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Rempel, N., Callaway, C. & Geyer, M. Serotonin1B Receptor

Activation Mimics Behavioral Effects of Presynaptic Serotonin Release. _Neuropsychopharmacol_ 8, 201–211 (1993). https://doi.org/10.1038/npp.1993.22 Download citation * Received: 11 October

1991 * Revised: 07 July 1992 * Accepted: 09 July 1992 * Issue Date: 01 May 1993 * DOI: https://doi.org/10.1038/npp.1993.22 SHARE THIS ARTICLE Anyone you share the following link with will

be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt

content-sharing initiative KEYWORDS * Locomotor activity * Serotonin * Investigatory behavior * Holeboard * RU 24969 * MDMA * Serotonin1B receptors