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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2023.tde-10112023-163259
Document
Author
Full name
Núbia Barros Pereira da Silva
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2023
Supervisor
Committee
Guimaraes, Elaine Aparecida Del Bel Belluz (President)
Sales, Amanda Juliana
Thomas, Liana Melo
Title in Portuguese
Catalepsia induzida por haloperidol: eficácia do canabigerol isolado e associado ao canabidiol
Keywords in Portuguese
Antipsicótico típico
Canabinoides
Catalepsia
Serotonina
Abstract in Portuguese
O haloperidol é um composto antipsicóticos típico utilizado no tratamento dos sintomas negativos da esquizofrenia. Apesar dos seus benefícios apresenta efeitos secundários, induzindo a catalepsia em roedores, distúrbio motor denominado parkinsonismo induzido por drogas. O canabidiol (CBD) e o canabigerol (CBG) são compostos canabinoides não psicotomiméticos extraídos da planta Cannabis sativa. Há evidências que estes compostos atuem como antipsicóticos atípicos em roedores e humanos. Neste estudo, investigamos se o CBG isoladamente ou a combinação CBG/CBD apresenta efeito benéfico neste distúrbio motor induzido pelo haloperidol (0,3mg/kg; s.c). Avaliamos se o CBG preveniria a catalepsia induzida por haloperidol e a indução da proteína c-Fos no corpo estriado. Para isso, camundongos Suíços machos adultos receberam pré-tratamento com CBG nas doses 0,3, 1,0, 3,0 ou 10 mg/k (i.p) 15 minutos antes do haloperidol. A dose de CBG (0,3mg/kg) atenuou a catalepsia. O tratamento com haloperidol aumentou a expressão da proteína c-Fos no estriado não alcançando significância estatística. O pré-tratamento com CBG nas diferentes doses não alterou a expressão da proteína c-Fos. Avaliamos possível efeito de combinações CBD/CBG utilizando diferentes doses de cada composto. CBG 3mg/kg + CBD 15mg/kg doses que administradas separadamente não apresentaram efeito, quando combinados atenuaram a catalepsia induzida pelo haloperidol sendo este efeito bloqueada pelo inibidor de receptor 5-HT1A (WAY100635, 0,1 mg/kg). Em contraste, o CBG na dose de 10mg/kg bloqueou o efeito anticataléptico do CBD 30mg/kg. Em conclusão, o CBG modula a catalepsia induzida pelo haloperidol e os compostos combinados apresentaram efeitos opostos dependendo das doses utilizadas. Os resultados sugerem que a interação depende da dose dos canabinoides e envolve a participação de receptores serotonérgicos.
Title in English
Haloperidol- induced catalepsy: efficacy of cannabigerol isolate and associated with cannabidiol
Keywords in English
Cannabinoids
Catalepsy
Serotonin
Typical antipsychotic
Abstract in English
Haloperidol is a typical antipsychotic compound used to treat the negative symptoms of schizophrenia. Despite its benefits it has side effects, inducing catalepsy in rodents, a motor disorder called drug-induced Parkinsonism. Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotomimetics cannabinoid compounds extracted from the Cannabis sativa plant. There is evidence that these compounds act as atypical antipsychotics in rodents and humans. In this study, we investigated whether CBG alone or the combination CBG/CBD shows beneficial effect in this motor disorder induced by haloperidol (0.3mg/kg; s.c). We evaluated whether CBG would prevent haloperidol-induced catalepsy and c-Fos protein induction in the striatum. To this end, adult male Swiss mice received CBG pretreatment at doses of 0.3, 1.0, 3.0 or 10 mg/k (i.p) 15 min before haloperidol. The CBG dose (0.3mg/kg) attenuated catalepsy. Haloperidol treatment increased c-Fos protein expression in striatum not reaching statistical significance. CBG pre-treatment at different doses did not alter c-Fos protein expression. We evaluated possible effect of CBD/CBG combinations using different doses of each compound. CBG 3mg/kg + CBD 15mg/kg doses that administered separately showed no effect, when combined attenuated haloperidol-induced catalepsy being this effect blocked by 5-HT1A receptor inhibitor (WAY100635, 0.1 mg/kg). In contrast, CBG at a dose of 10mg/kg blocked the anti-cataleptic effect of CBD 30mg/kg. In conclusion, CBG modulates haloperidol-induced catalepsy and the combined compounds showed opposite effects depending on the used doses. The interaction depends on the dose of the cannabinoids and involves the participation of serotonergic receptors.
 
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Publishing Date
2023-12-18
 
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