Most cited article - PubMed ID 30949045
The Cannabinoid CB1 Antagonist TM38837 With Limited Penetrance to the Brain Shows Reduced Fear-Promoting Effects in Mice
In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood.
- Keywords
- 2-arachidonoylglycerol (2-AG), AM251, MAM model, cannabinoid CB1 receptor, endocannabinoid system, schizophrenia,
- MeSH
- Rats MeSH
- Methylazoxymethanol Acetate * MeSH
- Disease Models, Animal MeSH
- Rats, Sprague-Dawley MeSH
- Receptor, Cannabinoid, CB1 MeSH
- Schizophrenia * chemically induced drug therapy genetics MeSH
- Pregnancy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Methylazoxymethanol Acetate * MeSH
- Receptor, Cannabinoid, CB1 MeSH