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Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release.
Neuropsychopharmacology. 1993 May; 8(3):201-11.N

Abstract

The locomotor hyperactivity induced by 3,4-methylene-dioxymethamphetamine (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-HT1C/2 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.

Authors+Show Affiliations

Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093-0804.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8099482

Citation

Rempel, N L., et al. "Serotonin1B Receptor Activation Mimics Behavioral Effects of Presynaptic Serotonin Release." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 8, no. 3, 1993, pp. 201-11.
Rempel NL, Callaway CW, Geyer MA. Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release. Neuropsychopharmacology. 1993;8(3):201-11.
Rempel, N. L., Callaway, C. W., & Geyer, M. A. (1993). Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 8(3), 201-11.
Rempel NL, Callaway CW, Geyer MA. Serotonin1B Receptor Activation Mimics Behavioral Effects of Presynaptic Serotonin Release. Neuropsychopharmacology. 1993;8(3):201-11. PubMed PMID: 8099482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release. AU - Rempel,N L, AU - Callaway,C W, AU - Geyer,M A, PY - 1993/5/1/pubmed PY - 1993/5/1/medline PY - 1993/5/1/entrez SP - 201 EP - 11 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 8 IS - 3 N2 - The locomotor hyperactivity induced by 3,4-methylene-dioxymethamphetamine (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-HT1C/2 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. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/8099482/Serotonin1B_receptor_activation_mimics_behavioral_effects_of_presynaptic_serotonin_release_ DB - PRIME DP - Unbound Medicine ER -