Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice.
A B Klein, Martin A. Santini, Susana Aznar, Gitte M. Knudsen, M Rios
Neuroscience September 1, 2010 DOI: 10.1016/j.neuroscience.2010.05.054 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Mutant mice with central depletion of BDNF (BDNF(2L/2LCk-cre)) and wildtype mice |
| Measures | [(3)H]-MDL100907 autoradiography, [(3)H]-WAY100635 autoradiography, 5-HT2A and 5-HT1A mRNA expression, 5-HT2C content, head-twitch response (HTR), ear-scratch response (ESR) |
| Topics | Serotonin |
| Key findings | BDNF-depleted mice showed lower frontal cortical 5-HT2A receptor binding but higher hippocampal 5-HT2A binding, and decreased hippocampal 5-HT1A binding with unchanged frontal 5-HT1A binding, paralleled by mRNA changes. Functionally, DOI-induced ear-scratch responses were diminished while head-twitch responses were unaffected, which the authors interpret as context-dependent effects of deficient BDNF signaling on the serotonin receptor system. |
Abstract
Changes in brain-derived neurotrophic factor (BDNF) expression have been implicated in the etiology of psychiatric disorders. To investigate pathological mechanisms elicited by perturbed BDNF signaling, we examined mutant mice with central depletion of BDNF (BDNF(2L/2LCk-cre)). A severe impairment specific for the serotonin 2A receptor (5-HT(2A)R) in prefrontal cortex was described previously in these mice. This is of much interest, as 5-HT(2A)Rs have been linked to neuropsychiatric disorders and anxiety-related behavior. Here we further characterized the serotonin receptor alterations triggered by BDNF depletion. 5-HT(2A) ([(3)H]-MDL100907) and 5-HT(1A) ([(3)H]-WAY100635) receptor autoradiography revealed site-specific alterations in BDNF mutant mice. They exhibited lower 5-HT(2A) receptor binding in frontal cortex but increased binding in hippocampus. Additionally, 5-HT(1A) receptor binding was decreased in hippocampus of BDNF mutants, but unchanged in frontal cortex. Molecular analysis indicated corresponding changes in 5-HT(2A) and 5-HT(1A) mRNA expression but normal 5-HT(2C) content in these brain regions in BDNF(2L/2LCk-cre) mice. We investigated whether the reduction in frontal 5-HT(2A)R binding was reflected in reduced functional output in two 5-HT(2A)-receptor mediated behavioral tests, the head-twitch response (HTR) and the ear-scratch response (ESR). BDNF(2L/2LCk-cre) mutants treated with the 5-HT(2A) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) showed a clearly diminished ESR but no differences in HTR compared to wildtypes. These findings illustrate the context-dependent effects of deficient BDNF signaling on the 5-HT receptor system and 5-HT(2A)-receptor functional output.
Comparable studies
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| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
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| 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 6
- 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review. ACS Pharmacology & Translational Science June 14, 2024
- Automated Computer Software Assessment of 5-Hydroxytryptamine 2A Receptor-Mediated Head Twitch Responses from Video Recordings of Mice ACS Pharmacology & Translational Science April 8, 2022
- [Neurotrophic mechanisms of psychedelic therapy]. Biologie aujourd'hui 2019
- Changing your mind: neuroplastic mechanisms underlying the therapeutic effect of psychedelics in depression, PTSD, and addiction Progress in Neuro-Psychopharmacology and Biological Psychiatry October 1, 2025
- The renaissance in psychedelic research: What do preclinical models have to offer. Progress in Brain Research 2018
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