RESUMO
RATIONALE: The neuropeptide galanin has been implicated in a wide range of pathological conditions in which frontal and temporal structures are compromised. It works through three subtypes of G-protein-coupled receptors. One of these, the galanin receptor 1 (Gal-R1) subtype, is densely expressed in the ventral hippocampus (vHC) and ventral prefrontal cortex (vPFC); two brain structures that have similar actions on behavioral control. We hypothesize that Gal-R1 contributes to cognitive-control mechanisms that require hippocampal-prefrontal cortical circuitry. OBJECTIVE: To examine the effect of local vHC and vPFC infusions of M617, a Gal-R1 agonist, on inhibitory mechanisms of response control. METHODS: Different cohorts of rats were implanted with bilateral guide cannulae targeting the vPFC or the vHC. Following infusion of the Gal-R1 agonist, we examined the animals' behavior using a touchscreen version of the 5-choice reaction time task (5-choice task). RESULTS: The Gal-R1 agonist produced opposing behaviors in the vPFC and vHC, leading to disruption of impulse control when infused in the vPFC but high impulse control when infused into the vHC. This contrast between areas was accentuated when we added variability to the timing of the stimulus, which led to long decision times and reduced accuracy in the vPFC group but a general improvement in performance accuracy in the vHC group. CONCLUSIONS: These results provide the first evidence of a selective mechanism of Gal-R1-mediated modulation of impulse control in prefrontal-hippocampal circuitry.
Assuntos
Galanina/análogos & derivados , Hipocampo/fisiologia , Comportamento Impulsivo/fisiologia , Córtex Pré-Frontal/fisiologia , Receptor Tipo 1 de Galanina/agonistas , Receptor Tipo 1 de Galanina/fisiologia , Animais , Bradicinina/administração & dosagem , Bradicinina/análogos & derivados , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Relação Dose-Resposta a Droga , Galanina/administração & dosagem , Galanina/fisiologia , Hipocampo/efeitos dos fármacos , Comportamento Impulsivo/efeitos dos fármacos , Infusões Intraventriculares , Masculino , Fragmentos de Peptídeos/administração & dosagem , Estimulação Luminosa/métodos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Long-Evans , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologiaRESUMO
The present experiments have been carried out in order to study (comparatively) oxidative stress and its consequences (i.e. modifications of DNA bases and/or DNA fragmentation), cell cycle progression (through two generations) and apoptosis in C6 glioma cells (with normal p53 status) and p53-null mouse embryonic fibroblasts (MEF) after incubation with fumonisin B(1) (FB(1)). Further endpoints, including protein and DNA syntheses as well as cytotoxicity, have been also studied. The results show that FB(1) (incubation) produced a significant increase of malondialdehyde (MDA) production (suggestive of lipid peroxidation) which was prevented by antioxidant agents in both cell types. Moreover, FB(1) induced a significant and dose-related increase of 8-OH-dG and DNA fragmentation in both C6 glioma and MEF cells. Unlike MEF cells, apoptotic C6 glioma cells were observed after FB(1) incubation. Moreover, suppression of cell cycle progression was observed in C6 glioma but not in MEF cell incubated with FB(1). The results suggest a possible loss of protective mechanisms (such as p53-dependent apoptosis and cell cycle arrest) in FB(1)-damaged MEF cells and confirm that cells lacking of mechanisms governed by p53 gene would be more susceptible to neoplastic cascade or mutation following DNA lesions induced by this mycotoxin.