AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents
| Autor: | Michal Arad, Jeanne Stemmelin, Caroline Cohen, Yaw Senyah, Beth Borowsky, Philippe Pichat, Stevens Rachel, Amaya De Levie, Segev Barak, Odessa Giardino, Guy Griebel, Geoffrey B. Varty, Robert E. Featherstone, Ina Weiner, Mark D. Black, Nancy Rogacki |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Psychosis Cannabinoid receptor medicine.medical_treatment Conditioning Classical Drug Evaluation Preclinical Mice Inbred Strains Pharmacology Anxiety Weight Gain Rats Sprague-Dawley Mice Cognition Receptor Cannabinoid CB1 mental disorders medicine Animals Antipsychotic Effects of cannabis Catalepsy Sulfonamides Behavior Animal Hydrocarbons Halogenated musculoskeletal neural and ocular physiology food and beverages Psychotomimetic medicine.disease Endocannabinoid system Rats Amphetamine Disease Models Animal nervous system Acoustic Stimulation Schizophrenia Evoked Potentials Auditory lipids (amino acids peptides and proteins) Drug Therapy Combination Cannabinoid Psychology medicine.drug Antipsychotic Agents |
| Zdroj: | Psychopharmacology. 215(1) |
| ISSN: | 1432-2072 |
| Popis: | The psychotomimetic effects of cannabis are believed to be mediated via cannabinoid CB1 receptors. Furthermore, studies have implicated CB1 receptors in the pathophysiology of schizophrenia.These studies investigated the effects of the CB1 receptor antagonist, AVE1625, in acute pharmacological and neurodevelopmental models of schizophrenia. AVE1625 was administered to rodents alone or as a co-treatment with clinically used antipsychotic drugs (APDs).The antipsychotic potential of AVE1625 was tested using psychotomimetic-induced hyperactivity and latent inhibition (LI) deficit models. The procognitive profile was assessed using hole board, novel object recognition, auditory evoked potential, and LI techniques. In addition, the side-effect profile was established by measuring catalepsy, antipsychotic-induced weight gain, plasma levels of prolactin, and anxiogenic potential.AVE1625 (1, 3, and 10 mg/kg ip), reversed abnormally persistent LI induced by MK-801 or neonatal nitric oxide synthase inhibition in rodents, and improved both working and episodic memory. AVE1625 was not active in positive symptom models but importantly, it did not diminish the efficacy of APDs. It also decreased catalepsy and weight gain induced by APDs, suggesting that it may decrease APD-induced extrapyramidal side effects (EPS) and compliance. Unlike other CB1 antagonists, AVE1625 did not produce anxiogenic-like effects.These preclinical data suggest that AVE1625 may be useful to treat the cognitive deficits in schizophrenia and as a co-treatment with currently available antipsychotics. In addition, an improved side-effect profile was seen, with potential to ameliorate the EPS and weight gain issues with currently available treatments. |
| Databáze: | OpenAIRE |
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