RESUMEN
1. Hypothalamic insulin (HI) is well known for its role in feeding regulation. In addition, its concentration is modified in response to meals. Recent studies suggest that brain insulin participates in memory processes, possibly through stimulation by glucose. 2. The present microdialysis study focused on local in vivo regulation of HI by glucose and on the effects of aging on HI, since aging is characterized by deterioration of memory, body weight regulation, and central glucose utilization. Glucose (8 mM) infused for 5 min increased extracellular HI levels rapidly, by 4.6-fold, and cerebellar insulin levels by 0.4-fold only, suggesting a specific area-dependent regulation of HI by glucose. Neither insulinemia nor glycemia were affected, suggesting a central mechanism. The same dose of glucose induced a modest (0.4-fold), delayed (45 min) increase in hypothalamic serotonin, suggesting that the effect of glucose on HI is independent of a previously defined local serotonin-induced insulin release. HI levels in old normal weight rats were half the levels of young rats. In genetically old obese (fa/fa) Zucker rats, HI concentration was 30% of that in young normal rats, suggesting a deterioration of HI availability when aging and obesity are combined. 3. The above results, in line with recent considerations on a potential role of central insulin in learning and memory, suggest particular effects of HI on feeding and memory and probably on a specific "memory for food."
Asunto(s)
Conducta Alimentaria/fisiología , Insulina/fisiología , Aprendizaje/fisiología , Memoria/fisiología , Factores de Edad , Envejecimiento/metabolismo , Envejecimiento/fisiología , Animales , Conducta Alimentaria/efectos de los fármacos , Glucosa/administración & dosificación , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Inyecciones Intraventriculares , Insulina/metabolismo , Aprendizaje/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Microdiálisis , Obesidad/metabolismo , Potasio/administración & dosificación , Ratas , Ratas Mutantes , Ratas Wistar , Ratas Zucker , Serotonina/metabolismoRESUMEN
OBJECTIVE: The obesity of the Zucker rat is associated with numerous metabolic and neurochemical disturbances involving the central transmitters regulating feeding behaviour. Among them, the release of satiety-related monoamines from the median hypothalamus in response to a meal is enhanced in obese, as compared to normal, rats as though larger amounts of these amines were necessary to bring about satiety in obese rats. Besides, the obese Zucker rat has often been described as shorter-living than its lean congener. One of the reasons for the shorter longevity of the obese rat was investigated in this study: it could be an aggravation of its obesity-related central disturbances with age. METHODS: We assessed the response to a meal of the hypothalamic monoamines, dopamine and serotonin, in young (four month old) and old (twelve month old) lean (Fa-Fa) and obese (fa-fa) Zucker rats. The in vivo technique of microdialysis was used to combine behavioural recordings and continuous neurochemical assays. RESULTS: The exacerbation of monoamine release observed in young obese rats in response to a meal was no longer found in old obese rats. Serotonin increase during a meal weakened with aging, especially in obese rats. Dopamine (DA) response to a meal was completely reversed in old obese rats, with a decrease instead of the increase observed in the three other groups. CONCLUSION: The decrease of monoaminergic response to a meal with age is apparently the opposite to the enhanced release related to obesity. However, this does not correspond to an amelioration of the hyperphagia of the obese rats with age, as we could observe in parallel behavioural experiments, but rather to a decrease in neurotransmitter metabolism and thus in neuronal functioning.