RESUMO
RATIONALE: Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. OBJECTIVES: We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. METHODS: Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. RESULTS: A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. CONCLUSIONS: The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.
Assuntos
Canabidiol/farmacologia , Transtornos Cognitivos/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Animais , Canabidiol/administração & dosagem , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Sobrecarga de Ferro/complicações , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Ratos , Ratos WistarRESUMO
Here we show that a systemic injection of the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) ameliorated an aging-associated deficit in object recognition memory in rats when the injection was given immediately, but not 6h after training. NaB had no effect in younger rats with normal memory retention. The results indicate that HDACis can ameliorate aging-related memory impairments by influencing the early consolidation phase of memory formation.
Assuntos
Butiratos/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Reconhecimento Psicológico/efeitos dos fármacos , Animais , Butiratos/administração & dosagem , Butiratos/farmacologia , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/farmacologia , Injeções Intraperitoneais , Masculino , Ratos , Ratos WistarRESUMO
Alterations in attachment behavior might play a role in the dysfunction in social behavior displayed by autistic infants. Here we show that neonatal gastrin-releasing peptide receptor (GRPR) blockade induces a reduction in maternal odor preference, a task involving attachment behavior, in infant rats. These findings provide the first evidence that the GRPR regulates odor preference, supporting the view that the GRPR is involved in attachment and social behaviors.
Assuntos
Bombesina/análogos & derivados , Comportamento de Escolha/efeitos dos fármacos , Odorantes , Fragmentos de Peptídeos/farmacologia , Receptores da Bombesina/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Aprendizagem da Esquiva/efeitos dos fármacos , Bombesina/farmacologia , Masculino , RatosRESUMO
Abnormally high levels of iron are observed in the brain of patients suffering from neurodegenerative disorders. The mechanisms involved in iron accumulation in neurodegenerative disorders remain poorly understood. In the present study we investigated the effects of aging and neonatal iron overload on the mRNA expression of proteins critically involved in controlling iron homeostasis. Wistar rat pups received a single daily dose of vehicle or iron (10 mg/kg of b.w. of Fe(2+)), at postnatal days 12-14. The expression of Transferrin Receptor (TfR), H-Ferritin, and IRP2 were analyzed by a semi-quantitative reverse transcriptase polymerase chain reaction assay in cortex, hippocampus and striatum of rats sacrificed at three different ages (15-day-old; 90-day-old and 2-year old rats). Results indicate that TfR, H-ferritin, and IRP2 mRNA expression was differentially affected by aging and by neonatal iron treatment in all three brain regions. These findings might have implications for the understanding of iron homeostasis misregulation associated with neurodegenerative disorders.