5-HT modulation of auditory and visual sensorimotor gating: I. Effects of 5-HT releasers on sound and light prepulse inhibition in Wistar rats.
J H Kehne, R A Padich, T C McCloskey, Vicki L. Taylor, C J Schmidt
Psychopharmacology March 1996 DOI: 10.1007/bf02245609 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Wistar rats |
| Interventions | p-chloroamphetamine 3 4-methylenedioxymethamphetamine N-ethyl-3 fenfluramine clonidine MDL 28 618A |
| Dose | 10 mg/kg p-chloroamphetamine (neurotoxic dose) |
| Topics | Serotonin |
| Key findings | All four serotonin-releasing agents produced dose-related disruptions of auditory and visual prepulse inhibition in rats, with p-chloroamphetamine the most potent. Two manipulations that reduce serotonin release or deplete cortical serotonin attenuated fenfluramine's disruptive effect on prepulse inhibition but not its effect on baseline startle, indicating serotonin mediates the gating disruption. The authors argue these data support a potential role of excessive serotonin activity in the disrupted sensory gating seen in schizophrenia. |
Abstract
Increasing evidence suggests an important role for serotonin (5-HT) neurons 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 assessed the general role of 5-HT in modulating auditory and visual prepulse inhibition in Wistar rats. A general overactivation of central serotonerigic pathways was produced pharmacologically by four different agents which all shared the common property of releasing 5-HT, i.e., p-chloroamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-3,4-methylenedioxymethamphetamine, or fenfluramine. Within each test session, both sound and light prepulses were used to obtain a cross-modal assessment of auditory and visual sensory gating processes. All four 5-HT releasing agents produced dose-related disruptions of auditory and visual prepulse inhibition, with p-chloroamphetamine being the most potent. The releasers depressed baseline to varying degrees. The alpha 2-adrenergic agonist clonidine decreased baseline startle without substantially disrupting prepulse inhibition, demonstrating that the two effects were dissociable. Using fenfluramine as the most selective 5-HT releaser, two approaches were used to demonstrate 5-HT mediation of its disruptive effect on prepulse inhibition. In the first approach, the selective 5-HT uptake blocker MDL 28,618A was used to prevent fenfluramine-induced 5-HT release. In the second approach, prior exposure to a neurotoxic dose of p-chloroamphetamine (10 mg/kg) was used to produce a substantial, sustained depletion of cortical 5-HT, presumably reflecting the loss of 5-HT terminals. Both approaches reduced the disruptive effect of fenfluramine on auditory and visual prepulse inhibition, thereby demonstrating 5-HT mediation of these effects. Neither manipulation significantly affected the depressant effect of fenfluramine on startle baseline, demonstrating that the baseline-reducing and prepulse inhibition-reducing effects of fenfluramine could be dissociated. MDL 28,618A alone did not affect prepulse inhibition or basal startle levels, demonstrating an important functional difference between pharmacologically induced 5-HT uptake blockade and 5-HT release. In summary, these data indicate that serotonergic overactivation can disrupt auditory and visual sensorimotor gating as measured using sound and light prepulse inhibition in rats. These data support a potential role of excessive 5-HT activity as a contributing factor to disrupted sensory gating processes seen in schizophrenia and possibly other neuropsychiatric disorders.
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 7
- Acute Psychological and Neurophysiological Effects of MDMA in Humans Journal of Psychoactive Drugs June 1, 2002
- Mephedrone (4-Methylmethcathinone): Acute Behavioral Effects, Hyperthermic, and Pharmacokinetic Profile in Rats Frontiers in Psychiatry January 10, 2018
- Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies Addiction Research & Theory 2002
- Plasticity of the acoustic startle reflex in currently abstinent ecstasy (MDMA) users. Psychopharmacology May 2004
- Prepulse inhibition and habituation of acoustic startle response in male MDMA ('ecstasy') users, cannabis users, and healthy controls. Neuropsychopharmacology May 2004
and 2 more in the library
Cites 10
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Subjective Reports of the Effects of MDMA in a Clinical Setting Journal of Psychoactive Drugs October 1, 1986
- 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
- Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Use: Effects on Mood and Neuropsychological Function? The American Journal of Drug and Alcohol Abuse 1992
- ECSTACY: A Review of MDMA and MDA The International Journal of Psychiatry in Medicine December 1, 1987
and 5 more in the library