5-HT modulation of auditory and visual sensorimotor gating: II. Effects of the 5-HT2A antagonist MDL 100,907 on disruption of sound and light prepulse inhibition produced by 5-HT agonists in Wistar rats.
R A Padich, T C McCloskey, J H Kehne
Psychopharmacology March 1996 DOI: 10.1007/bf02245610 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rodents (preclinical animals used in prepulse inhibition testing) |
| Interventions | MDL 100 907 haloperidol fenfluramine MDMA DOI |
| Dose | 0.04 mg/kg, IP (MDL 100,907 ED50) |
| Measures | prepulse inhibition (auditory and visual) |
| Topics | Serotonin |
| Key findings | MDL 100,907 blocked the disruption of auditory prepulse inhibition produced by fenfluramine, MDMA, and DOI, indicating that these effects result from 5-HT2A receptor stimulation. Haloperidol did not alter these disruptions, suggesting no direct or indirect D2 receptor involvement. The receptor(s) underlying fenfluramine- or MDMA-induced disruption of visual prepulse inhibition remain unidentified. |
Abstract
Increasing evidence suggests an important role of 5-HT, and 5-HT2A receptors in particular, in the etiology and treatment of schizophrenia. The prepulse inhibition paradigm is used as a model for sensorimotor gating processes that are disrupted in schizophrenia. The present study used the selective serotonin2A (5-HT2A) antagonist and putative antipsychotic agent MDL 100,907 to evaluate the contribution of 5-HT2A receptors to the disruptions of prepulse inhibition produced by several 5-HT agonists. The D2 antagonist haloperidol was used to evaluate a possible interaction with dopamine neurons. Sound or light prepulses were used to measure the generality of these drug effects on cross-modal prepulse inhibition. In the first study, MDL 100,907 antagonized the disruptions of auditory prepulse inhibition produced by the 5-HT releasing agents fenfluramine and 3,4-methylenedioxymethamphetamine (MDMA). These effects on prepulse inhibition were modality-specific in that MDL 100,907 did not reverse the effects of the 5-HT releasers on visual prepulse inhibition. Haloperidol did not alter the disruptive effects of MDMA or fenfluramine on either auditory or visual prepulse inhibition. In the second study, the direct acting 5-HT2A/2C receptor agonist/hallucinogen (+)1-4-iodo-2,5-dimethoxyphenyl-2-aminopropane (DOI) consistently disrupted auditory prepulse inhibition, and this effect was blocked by MDL 100,907 but not by haloperidol. A dose-response analysis demonstrated that MDL 100,907 potently antagonized DOI disrupted auditory prepulse inhibition, with an ED50 of 0.04 mg/kg, IP. DOI did not consistently disrupt visual prepulse inhibition. In summary, these data indicate that, at least under the conditions of the present studies, the disruptions of auditory prepulse inhibition produced by fenfluramine, MDMA, and DOI result from stimulation of 5-HT2A receptors. Furthermore, these disruptions do not involve direct or indirect stimulation of D2 receptors. The identity of the 5-HT receptor(s) underlying the disruptive effects of fenfluramine or MDMA on visual prepulse inhibition has not yet been identified. MDL 100,907 may be generally useful in CNS disorders in which excessive 5-HT2A receptor tone disrupts sensory gating processes.
Comparable studies
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| Study | Year | Design | Participants |
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| 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 29
- Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers Neuropsychopharmacology September 28, 2011
- The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval Neuropsychopharmacology February 14, 2007
- Brain mechanisms of hallucinogens and entactogens Dialogues in Clinical Neuroscience December 31, 2001
- Topographic pharmaco‐EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers British Journal of Clinical Pharmacology June 1, 2002
- Effect of Hallucinogens on Unconditioned Behavior Current Topics in Behavioral Neurosciences 2016
and 24 more in the library
Cites 3
- The substituted amphetamines 3,4-methylenedioxymethamphetamine, methamphetamine, p-chloroamphetamine and fenfluramine induce 5-hydroxytryptamine release via a common mechanism blocked by fluoxetine and cocaine European Journal of Pharmacology May 1, 1992
- 5-HT modulation of auditory and visual sensorimotor gating: I. Effects of 5-HT releasers on sound and light prepulse inhibition in Wistar rats. Psychopharmacology March 1996
- Effects of the serotonin releasers 3,4-methylenedioxymethamphetamine (MDMA), 4-chloroamphetamine (PCA) and fenfluramine on acoustic and tactile startle reflexes in rats. Journal of Pharmacology and Experimental Therapeutics 1992