Serotonergic functions in arousal and motor activity.
Behavioural Brain Research 1996 DOI: 10.1016/0166-4328(96)00065-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA para-chloroamphetamine (PCA) alpha-ethyltryptamine RU 24969 amphetamine |
| Topics | Serotonin |
| Key findings | The authors argue that the predominant effect of serotonin releasers is locomotor activation, apparently mediated via postsynaptic 5-HT1B receptors, suggesting some endogenous serotonergic systems may normally activate rather than suppress motor output. Direct 5-HT1 and 5-HT2 agonists decrease locomotion, while indirect agonists such as MDMA increase it and reduce investigation, effects distinguished from dopamine releasers. |
Abstract
Changes in motor activity have long been used to characterize the effects of serotonergic manipulations. The prevailing view has been that serotonin typically inhibits motor output, often in reciprocity with catecholaminergic systems. Recent findings, however, indicate that the release of presynaptic serotonin by indirect agonists leads to a profound locomotor activation. Studies were performed in a behavioral pattern monitor (BPM). The BPM is an automated holeboard/activity apparatus measuring 30.5 x 61 cm, that allows detailed sequential analyses of both locomotor and investigatory behaviors. When tested under comparable conditions, direct agonists at both 5-HT1 and 5-HT2 receptors decrease locomotor activity in rats. With hallucinogenic 5-HT2 agonists, this effect is dependent upon the novelty of the test environment, indicating that these compounds increase the responsiveness of the animal to the threatening aspects of the novel environment. Indirect serotonin agonists, however, increase locomotor activity and decrease investigation of discrete stimuli in the environment. The activating effects of indirect agonists such as 3,4-methylenedioxy-methamphetamine (MDMA), para-chloroamphetamine (PCA), or alpha-ethyltryptamine are dependent upon the release of serotonin from presynaptic terminals and are mimicked by direct agonists at 5-HT1B receptors. Both behavioral analyses and studies with synthesis inhibitors and receptor antagonists clearly distinguish the MDMA-induced hyperactivity from that induced by amphetamine-like releasers of dopamine. Further supporting the relevance of 5-HT1B receptors to the activating effects of serotonin-releasing agents, MDMA exhibits reciprocal cross-tolerance with the 5-HT1B agonist RU 24969, but not with either 5-HT1A or 5-HT2 agonists or amphetamine. Thus, studies of locomotor and investigatory responses can be used to demonstrate and differentiate the effects of direct agonists at 5-HT1A, 5-HT1B, and 5-HT2 receptors as well as indirect serotonin agonists. The fact that the predominant effect of serotonin releasers is locomotor activation, apparently mediated via post-synaptic 5-HT1B receptors, suggests that some endogenous serotonergic systems may normally activate rather than suppress motor output.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 13
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- 3,4-Methylenedioxymethamphetamine (Ecstasy) Inhibits Dyskinesia Expression and Normalizes Motor Activity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Primates Journal of Neuroscience October 8, 2003
- Direct effects of 3,4‐methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphé nucleus slices Synapse April 27, 2000
- An Appraisal of the Pharmacological and Toxicological Effects of a Single Oral Administration of 3,4‐Methylenedioxymethamphetamine (MDMA) in the Rat Pharmacology & Toxicology May 1, 1997
- Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies Addiction Research & Theory 2002
and 8 more in the library
Cites 14
- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class Journal of Medicinal Chemistry October 1, 1986
- 5HT-2 mediation of acute behavioral effects of hallucinogens in rats Psychopharmacology March 1, 1990
- Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists. Psychopharmacology 1991
- Cross-tolerance studies of serotonin receptors involved in behavioral effects of LSD in rats. Psychopharmacology January 1994
- Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release. Neuropsychopharmacology May 1, 1993
and 9 more in the library