RESUMEN
RATIONALE: Studies employing the Iowa Gambling Task (IGT) demonstrated that areas of the frontal cortex, including the ventromedial prefrontal cortex, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex, and anterior cingulate cortex (ACC), are involved in the decision-making process. However, the precise role of these regions in maintaining optimal choice is not clear. OBJECTIVES: We used the rat gambling task (rGT), a rodent analogue of the IGT, to determine whether inactivation of or altered dopamine signalling within discrete cortical sub-regions disrupts decision-making. METHODS: Following training on the rGT, animals were implanted with guide cannulae aimed at the prelimbic (PrL) or infralimbic (IL) cortices, the OFC, or the ACC. Prior to testing, rats received an infusion of saline or a combination of baclofen and muscimol (0.125 µg of each/side) to inactivate the region and an infusion of a dopamine D2 receptor antagonist (0, 0.1, 0.3, and 1.0 µg/side). RESULTS: Rats tended to increase their choice of a disadvantageous option and decrease their choice of the optimal option following inactivation of either the IL or PrL cortex. In contrast, OFC or ACC inactivation did not affect decision-making. Infusion of a dopamine D2 receptor antagonist into any sub-region did not alter choice preference. CONCLUSIONS: Online activity of the IL or PrL cortex is important for maintaining an optimal decision-making strategy, but optimal performance on the rGT does not require frontal cortex dopamine D2 receptor activation. Additionally, these results demonstrate that the roles of different cortical regions in cost-benefit decision-making may be dissociated using the rGT.
Asunto(s)
Conducta Animal/efectos de los fármacos , Toma de Decisiones/efectos de los fármacos , Lóbulo Frontal/efectos de los fármacos , Agonistas de Receptores de GABA-A/farmacología , Muscimol/farmacología , Animales , Baclofeno/farmacología , Conducta de Elección/efectos de los fármacos , Antagonistas de los Receptores de Dopamina D2/farmacología , Agonistas de Receptores GABA-B/farmacología , Juego de Azar , Masculino , Ratas , Ratas Long-EvansRESUMEN
Autoinhibitory serotonin 1A receptors (5-HT(1A)) in dorsal raphé nucleus (DRN) have been implicated in chronic depression and in actions of selective serotonin reuptake inhibitors (SSRI). Due to experimental limitations, it was never studied at single-cell level whether changes in 5-HT(1A) receptor functionality occur in depression and during SSRI treatment. Here we address this question in a social stress paradigm in rats that mimics anhedonia, a core symptom of depression. We used whole cell patch-clamp recordings of 5-HT- and baclophen-induced G-protein-coupled inwardly rectifying potassium (GIRK) currents as a measure of 5-HT(1A)- and GABA(B) receptor functionality. 5-HT(1A)- and GABA(B) receptor-mediated GIRK-currents were not affected in socially stressed rats, suggesting that there was no abnormal (auto)inhibition in the DRN on social stress. However, chronic fluoxetine treatment of socially stressed rats restored anticipatory behavior and reduced the responsiveness of 5-HT(1A) receptor-mediated GIRK currents. Because GABA(B) receptor-induced GIRK responses were also suppressed, fluoxetine does not appear to desensitize 5-HT(1A) receptors but rather one of the downstream components shared with GABA(B) receptors. This fluoxetine effect on GIRK currents was also present in healthy animals and was independent of the animal's "depressed" state. Thus our data show that symptoms of depression after social stress are not paralleled by changes in 5-HT(1A) receptor signaling in DRN neurons, but SSRI treatment can alleviate these behavioral symptoms while acting strongly on the 5-HT(1A) receptor signaling pathway.
Asunto(s)
Fluoxetina/uso terapéutico , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/fisiología , Núcleos del Rafe/efectos de los fármacos , Receptor de Serotonina 5-HT1A/fisiología , Receptores de GABA-B/fisiología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Estrés Fisiológico/tratamiento farmacológico , Análisis de Varianza , Animales , Baclofeno/farmacología , Conducta Animal , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Agonistas del GABA/farmacología , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Potenciales de la Membrana/efectos de la radiación , Neuronas/efectos de los fármacos , Neuronas/fisiología , Técnicas de Placa-Clamp , Núcleos del Rafe/fisiopatología , Ratas , Ratas Wistar , Serotonina/farmacologíaRESUMEN
The influence of housing temperature in early life on subsequent growth and development of broiler chickens was investigated. Hatchlings were exposed to an ambient temperature of 34 degrees C (NT) or 28 degrees C (LT) on d 1. Both temperature regimes decreased with 1 degrees C per day for 5 d. At d 6 the ambient temperature of the LT group was increased to the same ambient temperature as the NT group. At d 29 all chickens were exposed to 10 degrees C for 7 d. Navel temperature was lower in the LT group than in the NT group from d 2 to 5. Body weight of the chickens was higher in the NT group than in the LT group and the difference between both groups increased in time. Temperature treatment during the early post-hatching period did not result in a long-term alternation in organ development, haematocrit value, energy and protein metabolism or the occurrence of ascites. Although not significantly, the course of metabolism suggested that early thermal treatment had long-term effects. Before cold treatment in week 5, the NT group showed higher values for energy and protein metabolism than the LT group, but during cold exposure, the opposite was found. We concluded that exposure of chickens to a moderate reduction in house temperatures during early post-hatching life seemed to have long-term negative effects on the performance of these chickens, but, on the other hand, it seemed that these chickens were better prepared to withstand cold challenge later in life.