ArticlePsychopharmacology2016
Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism.
Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Prenatal stress and fluoxetine exposure in BTBR and B6 mice differentially affects autism-like behaviors in adult male and female offspring.Physiology & behavior · 2025Article
- Functional Food Nutrients, Redox Resilience Signaling and Neurosteroids for Brain Health.International journal of molecular sciences · 2024Review
- Prolonged HPA axis dysregulation in postpartum depression associated with adverse early life experiences: A cross-species translational study.Nature. Mental health · 2024Article
- Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target.Science advances · 2024Article
- Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling.Molecular autism · 2023Article
- Maturation of nucleus accumbens synaptic transmission signals a critical period for the rescue of social deficits in a mouse model of autism spectrum disorder.Molecular brain · 2023Article
- Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR andFrontiers in neuroscience · 2023Article
- Neuroanatomical changes of ionotropic glutamatergic and GABAergic receptor densities in male mice modeling idiopathic and syndromic autism spectrum disorder.Frontiers in psychiatry · 2023Article
- Morphine reduces the interest for natural rewards.Psychopharmacology · 2022Article
- Social deficits in BTBR T+ Itpr3tf/J mice vary with ecological validity of the test.Genes, brain, and behavior · 2022Article
- GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAPharmacology & therapeutics · 2022Review
- The eIF4E homolog 4EHP (eIF4E2) regulates hippocampal long-term depression and impacts social behavior.Molecular autism · 2020Article
- Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism.Molecular psychiatry · 2020Article
- Behavioral Evaluation of Angelman Syndrome Mice at Older Ages.Neuroscience · 2020Article
- Evaluation of a TrkB agonist on spatial and motor learning in theLearning & memory (Cold Spring Harbor, N.Y.) · 2020Article
- Vitexin Possesses Anticonvulsant and Anxiolytic-Like Effects in Murine Animal Models.Frontiers in pharmacology · 2020Article
- Hypothesis-driven investigations of diverse pharmacological targets in two mouse models of autism.Autism research : official journal of the International Society for Autism Research · 2019Article
- Reduced Neurosteroid Exposure Following Preterm Birth and Its' Contribution to Neurological Impairment: A Novel Avenue for Preventative Therapies.Frontiers in physiology · 2019Review
- MeCP2 isoform e1 mutant mice recapitulate motor and metabolic phenotypes of Rett syndrome.Human molecular genetics · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationaleAbnormalities in excitatory/inhibitory neurotransmission are hypothesized to contribute to autism spectrum disorder (ASD) etiology. BTBR T (+) Itpr3 (tf) /J (BTBR), an inbred mouse strain, displays social deficits and repetitive self-grooming, offering face validity to ASD diagnostic symptoms. Reduced GABAergic neurotransmission in BTBR suggests that GABAA receptor positive allosteric modulators (PAMs) could improve ASD-relevant BTBR phenotypes. The neuroactive steroid ganaxolone acts as a PAM, displaying anticonvulsant properties in rodent epilepsy models and an anxiolytic-like profile in the elevated plus-maze.
objectivesWe evaluated ganaxolone in BTBR and C57BL/6J mice in standardized assays for sociability and repetitive behaviors. Open field and anxiety-related behaviors were tested as internal controls and for comparison with the existing neuroactive steroid literature.
resultsGanaxolone improved aspects of social approach and reciprocal social interactions in BTBR, with no effect on repetitive self-grooming, and no detrimental effects in C57BL/6J. Ganaxolone increased overall exploratory activity in BTBR and C57BL/6J in the open field, social approach, and elevated plus-maze, introducing a confound for the interpretation of social improvements. Allopregnanolone and diazepam similarly increased total entries in the elevated plus-maze, indicating that behavioral activation may be a general property of GABAA receptor PAMs in these strains.
conclusionsGanaxolone shows promise for improving sociability. In addition, ganaxolone, as well as other GABAA receptor PAMs, enhanced overall BTBR activity. The translational implications of specific sociability improvements and nonspecific behavioral activation by ganaxolone in the BTBR model remain to be determined. Future studies to explore whether PAMs provide a novel profile with unique benefits for ASD treatment will be worthwhile.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.