3α5β-Pregnanolone glutamate, a use-dependent NMDA antagonist, reversed spatial learning deficit in an animal model of schizophrenia
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22820236
DOI
10.1016/j.bbr.2012.07.020
PII: S0166-4328(12)00476-7
Knihovny.cz E-resources
- MeSH
- Dizocilpine Maleate MeSH
- Glutamates pharmacology therapeutic use MeSH
- Cognition Disorders complications drug therapy MeSH
- Rats MeSH
- Disease Models, Animal * MeSH
- Motor Activity drug effects MeSH
- Rats, Long-Evans MeSH
- Pregnanolone analogs & derivatives pharmacology therapeutic use MeSH
- Receptors, N-Methyl-D-Aspartate antagonists & inhibitors MeSH
- Schizophrenic Psychology * MeSH
- Schizophrenia complications drug therapy MeSH
- Avoidance Learning drug effects MeSH
- Anxiety complications drug therapy MeSH
- Vocalization, Animal drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 20-oxo-5-pregnan-3-yl-glutamyl 1-ester MeSH Browser
- Dizocilpine Maleate MeSH
- Glutamates MeSH
- Pregnanolone MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
Neuroactive steroids modulate receptors for neurotransmitters in the brain and thus might be efficacious in the treatment of various diseases of the central nervous system such as schizophrenia. We have designed and synthetized a novel use-dependent NMDA receptor antagonist 3α5β-pregnanolone glutamate (3α5β-P-Glu). In this study, we evaluate procognitive properties of 3α5β-P-Glu in an animal model of schizophrenia induced by systemic application of MK-801. The procognitive properties were evaluated using active place avoidance on a rotating arena (Carousel maze). We evaluated effects of 3α5β-P-Glu on the avoidance, on locomotor activity, and anxiety. 3α5β-P-Glu alone altered neither spatial learning nor locomotor activity in control animals. In the model animals, 3α5β-P-Glu reversed the MK-801-induced cognitive deficit without reducing hyperlocomotion. The highest dose of 3α5β-P-Glu also showed anxiolytic properties. Taken together, 3α5β-P-Glu may participate in the restoration of normal brain functioning and these results may facilitate the development of new promising drugs improving cognitive functioning in schizophrenia.
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