ABSTRACT
Resumen: El objetivo principal de la presente investigación fue evaluar los efectos del agonista 5-HT2C Ro 60-0175 en la expresión de la sensibilización locomotora inducida por la administración de etanol. Además, también se evaluaron los efectos del antagonista 5-HT2C SB 242084 sobre los efectos del Ro 60-0175 en la sensibilización locomotora producida por etanol para determinar si los efectos del Ro 60-0175 resultan de una acción específica sobre los receptores 5-HT2C. Diferentes grupos de ratas se sometieron al desarrollo de sensibilización locomotora producida por etanol. En las pruebas de expresión de la sensibilización locomotora se evaluaron los efectos del Ro 60-0175 y del SB 242084 sobre la sensibilización locomotora producida por etanol. Adicionalmente se evaluó el pretratamiento con SB 242084 sobre los efectos del Ro 60-0175 en la sensibilización locomotora producida por etanol. Los resultados mostraron que el Ro 60-0175 disminuyó la sensibilización locomotora producida por etanol y que este efecto fue prevenido por el pretratamiento con SB 242084. Estos resultados sugieren que los receptores 5-HT2C juegan un papel modulatorio en la sensibilización locomotora producida por etanol.
Abstract: The main goal of the present research was to evaluate the effects of 5-HT2C receptor agonist Ro 60-0175 on the expression of ethanol-induced locomotor sensitization. In order to determine if these effects result from a specific action of Ro 60-0175 on 5-HT2C receptors, we also examined the effects of the selective 5-HT2C receptor antagonist SB 242084 on Ro 60-0175's effects on the ethanol-induced locomotor sensitization. Different groups of rats were subjected to development of ethanol-induced locomotor sensitization. On the expression tests of the locomotor sensitization the effects of the Ro 60-0175 and SB 242084 on the ethanol-induced locomotor sensitization were evaluated. In addition, the pretreatment with SB 242084 on the effects of Ro 60-0175 on the ethanol-induced locomotor sensitization was also evaluated. The results showed that Ro 60-0175 produced a dose-dependent prevention of the expression of ethanol-induced locomotor sensitization. This effect was reversed by administration of SB 242084. These data suggest that 5-HT2C receptors play a regulatory role on ethanol-induced locomotor sensitization.
ABSTRACT
This study investigated the effects of two selective serotonin2C (5-hydroxytryptamine, 5-HT2C) receptor-acting compounds into the ventral hippocampus (VH) of rats exposed to the elevated plus-maze (EPM). In the first experiment, rats were exposed to the EPM 10 min following VH infusions of either vehicle or the selective 5-HT2C-receptor agonist RO-60-0175 (0.3, 1.0, 3.0 and 10.0µg). In addition to conventional parameters of open arm exploration (i.e. percentages of open arm entries and of time spent in these arms), risk assessmentrelated behaviors were recorded as anxiety-like measures in EPM scoring. RO-60-0175 selectively decreased open arm exploration at the dose of 1.0 µg, while inducing locomotor-suppressant effects at the two highest doses. In the second experiment, VH infusions of the selective 5-HT2C antagonist RS 102221 (0.75, 1.25 and 2.5 µg) did not affect open arm exploration, while reducing risk assessment in the closed ones. This behavioral profile of risk assessment is suggestive of an anxiolytic-like action. These results further corroborate our previous findings showing that VH 5-HT2C receptor activation elicits anxiogenic-like and locomotor-suppressant effects, and suggest that the selective blockade of this receptor is accompanied by an anxiolytic-like action as detected by ethologically derived measures in the EPM.