RESUMO
Orexin and its receptors are involved in the mechanisms of pathological craving for alcohol and psychoactive drugs. The orexin system is also involved in the mechanisms of non-chemical forms of addiction: binge eating and gambling. The aim of this work was to study the level of orexin receptor mRNA in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior in a model for studying the elements of gambling addiction (a variant of the Iowa Gambling Task test). Brain structures were isolated on the 22nd day of the experiment. The expression of the OX1R gene was higher in the hypothalamus by 122% and in the hippocampus by 149% in rats that preferred to receive a high reward, but with a low probability as compared with a group of animals that preferred a low level of reinforcement, but with a 100% probability. In the prefrontal cortex, on the contrary, no significant changes were observed in the level of OX1R mRNA. The level of OX2R mRNA insignificantly changed in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior. The data indicate involvement of OX1R in the hypothalamus and hippocampus in mechanisms mediating impulsive behavior and the choice of the significance of positive reinforcement in terms of its varying strength and probability.
Assuntos
Encéfalo , Hipotálamo , Animais , Comportamento Impulsivo , Receptores de Orexina/genética , RNA Mensageiro/genética , RatosRESUMO
The neurotransmitter systems of the brain are exposed to dysregulation during alcohol withdrawal. This contributes to the development of the pathological craving for alcohol in which corticotropin-releasing hormone receptors are may be involved. During the period of alcohol withdrawal, the level of CRFR2 mRNA in the ventral tegmental area of the brain on the seventh day of abstinence was significantly increased in comparison with the control group. This supports existing concepts on possible participation in the modulation of dopaminergic and GABA-neural neurons in the ventral tegmental area the brain.
Assuntos
Alcoolismo , Encéfalo/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Síndrome de Abstinência a Substâncias , Animais , Encéfalo/efeitos dos fármacos , Etanol , RNA Mensageiro , RatosRESUMO
Orexin and its receptors were shown to be involved into mechanisms of pathological craving to alcohol. This paper demonstrates that the orexin receptor type 1 (OX1R) mRNA level significantly decreased in the prefrontal cortex of rats chronically (during 6 months) consuming ethanol compared with intact control. The same results were observed on day 1 and day 7 of alcohol withdrawal after chronic alcoholization. On the contrary, in the hippocampus, the OX1R mRNA level increased on day 1 and day 7 of alcohol withdrawal. In the ventral tegmental area, the OX1R mRNA level did not change on the day 1 and day 7 of alcohol withdrawal compared with the groups of chronic alcoholization and intact control. These findings point out involvement of the prefrontal cortex and hippocampus first of all in mechanisms mediating chronic alcohol intoxication. The ventral tegmental area is described as a typical dopaminergic structure providing the executive mechanism of emotion reactions connected with alcohol abuse in particular. It is possibe, that the modulating action of orexins on dopaminergic neurons in this structure does not provide a significant effect on control of emotion reactions in alcoholism.