Efecto del 2-aminoindano rígido, derivado del acenafteno, sobre la conducta estereotipada de ratas. Papel del sistema dopaminérgico cerebral. / Effect of the rigid 2-aminoindano, derived from acenaphthene, on stereotyped behavior in rats. Role of brain dopaminergic system.
Abstract
Resumen.
Las enfermedades neurodegenerativas y neuropsiquiátricas se encuentran directamente relacionadas con alteraciones o disfuncionalidad del sistema dopaminérgico central. Entre las primeras encontramos la enfermedad de Parkinson (EP), la disquinesia tardía, el síndrome de Tourette, la Corea de Huntington (EH), y entre las segundas la Esquizofrenia (EZ), la adicción, la manía, la depresión, y los desórdenes de la alimentación. Con el fin de contribuir con el arsenal terapéutico que permita restaurar la homeostasis de la neurotransmisión dopaminérgica central, se evaluó farmacológicamente el clorhidrato del 1-amino-6,7,8,8a-tetrahidroacenafteno 2 (Ja116a) mediante la cuantificación de sus efectos sobre la conducta estereotipada de ratas. Se emplearon ratas machos de la cepa Sprague-Dawley, a las que se les implantó una cánula intracerebroventricular (ICV). El compuesto 2 (Ja116a) fue administrado por vía ICV (5µg/5µL y 50µg/5µL), en presencia o ausencia de apomorfina (APO), haloperidol (HAL), buspirona (BUS) o ziprasidona (ZIP); o por vía intraperitoneal (IP) (1mg/Kg) en ratas tratadas con APO o HAL. Igualmente, un grupo de ratas fue sometido a denervación dopaminérgica central mediante la 6OH-dopamina (6OHDA). Los resultados mostraron que Ja116a induce una conducta estereotipada de roídas y olfateos (sistema extrapiramidal) y acicalamientos y lamidas (sistema límbico), efectos que fueron bloqueados por el HAL y reducidos por la buspirona y la 6OHDA. Estos hallazgos indican que Ja116 actúa principalmente como un agonista dopaminérgico postsináptico, por lo que podría proponerse como un fármaco novedoso para el tratamiento de enfermedades neurodegenerativas tales como la Enfermedad de Parkinson.
Abstract.
Neurodegenerative and neuropsychiatric diseases are directly related to alterations or dysfunction of the central dopaminergic system. Among the first are Parkinson’s disease (PD), tardive dyskinesia, Tourette’s syndrome, Huntington’s chorea (HD), and among the second, Schizophrenia (EZ), addiction, mania, depression, and eating disorders. In order to contribute to the therapeutic arsenal that allows restoring the homeostasis of central dopaminergic neurotransmission, 1-amino-6,7,8,8a-tetrahydro acenaphthene 2 hydrochloride (Ja116a) was pharmacologically evaluated by quantification of its effects on stereotyped behavior in rats. Male Sprague-Dawley rats were used and were implanted with an intracerebroventricular cannula (ICV). Compound Ja116a was ICV administered (5µg/5µL and 50µg/5µL), in the presence or absence of apomorphine (APO); haloperidol (HAL); buspirone (BUS) or ziprasidone (ZIP); or intraperitoneally (IP) (1mg/Kg) in rats treated with APO or HAL. Similarly, a group of rats was subjected to central dopaminergic denervation by 6OH-dopamine (6OHDA). The results show that Ja116a induces a stereotypical behavior of gnawing and sniffing (extrapyramidal system) and grooming and licking (limbic system), effects that were blocked by HAL and reduced by buspirone and 6OHDA. These findings indicate that Ja116 acts mainly as a postsynaptic dopaminergic agonist, so it could be proposed as a novel drug for the treatment of neurodegenerative diseases such as Parkinson’s disease.
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References
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