Approche psychobiologique du vieillissement cérébral chez le rat : implications et modulations cholinergiques

Doctorat en sciences médicales -- UCL, 198

AIRES DE RÉSIDENCE PRÉFÉRENTIELLES D'UN GROUPE DE VACHES LAITIÈRES EN STABULATION LIBRE

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Cholinergic blockade and response timing in rats

The effects of central cholinergic blockade on the temporal regulation of behaviour were studied with a two-level DRL schedule. Five-month-old male Wistar rats had to press lever A and then wait for a minimum of 5 s before pressing lever B to obtain the reinforcer (sweetened milk). After a stable baseline performance, subjects were injected in random order with the general cholinergic blocker, scopolamine, 0.15 and 0.5 mg/kg, the peripheral cholinergic blocker, methylscopolamine, 0.15 and 0.5 mg/kg, and a combination of the cholinesterase inhibitor, physostigmine, 0.2 mg/kg, and scopolamine, 0.5 mg/kg. Each drug treatment was separated by 2 days of saline treatment. Results showed that scopolamine at 0.5 mg/kg significantly impaired the temporal regulation of the A-B response sequence: the median A-B inter-response time (IRT) was shortened and the coefficient of variation of the A-B IRT distribution was increased, thus revealing a loss in the sensitivity to time. This disruption of accurate timing behaviour lowered efficiency. The drug changed neither the duration of the B-A interval nor the A-B response rate, but significantly increased the rate of the superfluous B-B sequences. Methylscopolamine was without effects and physostigmine totally or partially reversed all the scopolamine effects. These results suggest that scopolamine at 0.5 mg/kg specifically affected the mechanism(s) underlying response timing, and that the effects were not secondary to changes in activity or motivation. They partly corroborate data obtained in other procedures and support the idea that the central cholinergic system is involved in the temporal regulation of behaviour

Anhedonic-like traits and lack of affective deficits in 18-month-old C57BL/6 mice: Implications for modeling elderly depression.

The prevalence of depression increases with aging. We hypothesized that like humans, old animals exhibit anhedonic-like behavior, along with signs of behavioral despair. In rodents, anhedonia, a reduced sensitivity to reward, which is listed as a core feature of major depression in the DSM-IVR, can be measured by a decrease in intake of and preference for sweet solutions. Here, sucrose intake, forced swimming, immobility in the modified tail suspension test, novelty exploration, grooming, anxiety and locomotor activity were compared in naive 3- and 18-month-old male C57BL/6 mice. The absolute amounts and the ratio of consumed 1% sucrose solution to water intake was significantly smaller in 18-month-old mice than in 3-month-old mice. The consumption of 5%-sucrose solution requiring high levels of drinking effort, novelty exploration in two setups and grooming behavior in the splash test were reduced in older animals. Analysis of other behaviors suggested that the above-mentioned signs of anhedonic-like traits were unlikely to be attributable to the potential effect of aging on metabolic needs for water, taste perception, motor capabilities or the induction of essential anxiety and neophobia. A 4-week treatment with the antidepressant imipramine (7mg/kg/day) or dimebon, a compound with suggested neuroprotective proneurogenic properties (1mg/kg/day) restored sucrose intake and preference in 18-month-old mice. Meanwhile, young and old mice showed no differences in the parameters of behavioral despair evaluated in the forced swim and modified tail suspension tests. Thus, the behavioral profile of aged mice parallels that of humans with elderly depression, in whom the symptoms of hedonic deficits typically outweigh affective disturbances. The assessment of anhedonic-like traits with the sucrose preference test in 18-month-old mice will be useful in preclinical studies of elderly depression

Effects of enriched environments with different durations and starting times on learning capacity during aging in rats assessed by a refined procedure of the Hebb-Williams maze task

Cognitive function as measured by the Hebb-Williams maze task was examined in Fischer 344 male rats that had been exposed to an enriched environment for periods of variable duration and at different starting ages. In one experiment, rats were exposed to environmental enrichment from weaning until the age of 2.5, 15, or 25 months. The results of 12 problems of the Hebb-Williams maze task showed that the enriched rearing condition improved the learning ability in all the age groups; however, factor analysis and ANOVA demonstrated that four of the 12 maze problems were not suitable for detecting the effect of age under different environmental conditions. Reanalysis of the results obtained with the other eight maze problems more clearly revealed both the effects of rearing condition and aging. The latter analysis demonstrated that the learning rate of rats reared under enriched conditions was faster than that of rats reared under standard social conditions. Short-term (3-month) exposure also had positive effects on cognitive function in both adult (11-month-old) and aged (22-month-old) animals. The effect of long-term exposure to an enriched environment starting at weaning was much greater than that of short-term exposure in aged. rats, whereas the effects of both long-term and short-term exposure were almost the same in adult rats. These results show that aged animals still have appreciable plasticity in cognitive function, and suggest that environmental stimulation could benefit aging humans as well. (C) 2002 Wiley-Liss, IncIn: Journal of Neuroscience Research, vol. 70, nr. 3, pp. 340-346Cognitive function as measured by the Hebb-Williams maze task was examined in Fischer 344 male rats that had been exposed to an enriched environment for periods of variable duration and at different starting ages. In one experiment, rats were exposed to environmental enrichment from weaning until the age of 2.5, 15, or 25 months. The results of 12 problems of the Hebb-Williams maze task showed that the enriched rearing condition improved the learning ability in all the age groups; however, factor analysis and ANOVA demonstrated that four of the 12 maze problems were not suitable for detecting the effect of age under different environmental conditions. Reanalysis of the results obtained with the other eight maze problems more clearly revealed both the effects of rearing condition and aging. The latter analysis demonstrated that the learning rate of rats reared under enriched conditions was faster than that of rats reared under standard social conditions. Short-term (3-month) exposure also had positive effects on cognitive function in both adult (11-month-old) and aged (22-month-old) animals. The effect of long-term exposure to an enriched environment starting at weaning was much greater than that of short-term exposure in aged. rats, whereas the effects of both long-term and short-term exposure were almost the same in adult rats. These results show that aged animals still have appreciable plasticity in cognitive function, and suggest that environmental stimulation could benefit aging humans as well. (C) 2002 Wiley-Liss, IncOnderzoeksbibliografie Frank OdbergHerkomst: Onderzoeksbibliografie van em. prof. dr. Frank O. Ödberg, verbonden aan de Vakgroep Voeding, Genetica en Ethologie van de Faculteit Diergeneeskund