Some behavioral effects of hallucinogens are mediated by a postsynaptic serotonergic action: evidence from single unit studies in freely moving cats.
J Heym, K Rasmussen, B L Jacobs
European Journal of Pharmacology May 18, 1984 DOI: 10.1016/0014-2999(84)90030-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment (pharmacological antagonist study in cats) Peer reviewed |
|---|---|
| Population | Cats |
| Interventions | Mianserin Ketanserin Metergoline LSD DOM Lisuride Apomorphine |
| Dose | 1.0 mg/kg mianserin, ketanserin, or metergoline; LSD 50 micrograms/kg; DOM 250 micrograms/kg; lisuride 50 micrograms/kg; apomorphine 4 mg/kg |
| Measures | cat limb flick response, mesencephalic serotonergic neuron discharge |
| Topics | Serotonin |
| Key findings | Serotonin receptor antagonists at behaviorally inactive doses blocked the limb flick response to LSD and DOM but not to lisuride or apomorphine, and mianserin blocked LSD's behavioral effect without altering LSD-induced depression of serotonergic neuron firing. The authors conclude that hallucinogen behavioral, and possibly psychoactive, effects are attributable to action at 5HT2 receptors, presumably located postsynaptically. |
Abstract
Although central serotonergic systems appear to be linked importantly to the mechanism of action of a variety of hallucinogenic drugs, the nature of this interaction has remained unclear. In the present study, the question of whether the critical link is presynaptic or postsynaptic was examined in cats. Behaviorally inactive doses (1.0 mg/kg) of the serotonin receptor antagonists mianserin, ketanserin or metergoline effectively blocked behavior, as measured by the cat limb flick response, elicited by either LSD (50 micrograms/kg) or DOM (250 micrograms/kg) but not that resulting either from lisuride (50 micrograms/kg) or a high dose of apomorphine (4 mg/kg). Pretreatment with 1.0 mg/kg of mianserin, which completely attenuated LSD's behavioral effect, failed to alter LSD-induced depression of mesencephalic serotonergic neuron discharge. These results demonstrate that at least some of the behavioral effects of LSD can be blocked by pharmacological antagonism of postsynaptic serotonin receptors which leaves LSD's presynaptic effect unaffected. Thus, the behavioral, and possibly psychoactive, effects of hallucinogens appear to be attributable to an action at 5HT2 receptors, presumably located postsynaptically.
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 10
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD) Psychopharmacology 1987
- Serotonin and the Action of LSD in the Brain Psychiatric Annals March 1, 1994
- Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists Psychopharmacology November 1, 1987
- Alpha-adrenergic and 5-HT2-serotonergic effects of some beta-phenylethylamines on isolated rat thoracic aorta. General pharmacology 1994
and 5 more in the library
Cites 7
- Prevention of the serotonin syndrome in rats by repeated administration of monoamine oxidase inhibitors but not tricyclic antidepressants. Psychopharmacology 1982
- Role of serotonin in the discriminative stimulus properties of mescaline Pharmacology, Biochemistry, and Behavior May 1, 1975
- DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines. European Journal of Pharmacology January 21, 1983
- Dissociations between the effects of hallucinogenic drugs on behavior and raphe unit activity in freely moving cats. Brain Research June 1, 1981
- The discriminative stimulus properties of 2,5-dimethoxy-4-methylamphetamine (DOM): differentiation from amphetamine. Psychopharmacology 1980
and 2 more in the library