RESUMEN
Converging lines of evidence suggest that oligomers of amyloid-beta play a role in the cognitive impairment characteristic of Alzheimer's disease, but only three studies have provided experimental evidence of such impairment. To provide additional information about the effects of these oligomers on memory, the present study examined the memory of groups of rats exposed to ICV injections of the culture media (CM) of Chinese Hamster Ovary cells that were (7PA2) and were not (CHO-) transfected with a human mutation of amyloid precursor protein that appears to cause early-onset Alzheimer's disease. The 7PA2 CM, which contained concentrations of soluble amyloid-beta oligomers physiologically relevant to those found in human brain, significantly disrupted working memory in rats tested in a radial-arm maze. In contrast, CHO- CM, which did not contain such oligomers, had no effect on memory. The disruptive effects of 7PA2-derived amyloid-beta oligomers, evident 2h after exposure, disappeared within a day. These findings are compared to results from 7PA2 CM tested under a complex procedure thought to measure aspects of executive function. The results confirm the disruptive effects of low-n amyloid-beta oligomers and extend them to a well-established rat model of memory.
Asunto(s)
Péptidos beta-Amiloides/toxicidad , Conducta Animal/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Conducta Animal/fisiología , Western Blotting , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Células CHO , Cricetinae , Cricetulus , Medios de Cultivo Condicionados/metabolismo , Medios de Cultivo Condicionados/toxicidad , Femenino , Humanos , Inyecciones Intraventriculares , Masculino , Peso Molecular , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/toxicidad , Ratas , Ratas Sprague-Dawley , TransfecciónRESUMEN
To examine whether CS-US pairing probability, hence rate (or probability) of food delivery, modulated the effects of cocaine, pigeons were exposed to an autoshaping procedure in which 6-s red, green, and white illuminations of a response key were immediately followed by response-independent food delivery with a probability of 1.0, 0.5, and 0.25, respectively. Substantial responding occurred at all probabilities. Pre- and post-chronic administrations of cocaine (1.0-17.8 mg/kg) produced dose-dependent decreases in mean percent trials (key illuminations) with a response and total responses per session at all probabilities. In general, sensitivity to the drug was lowest at the highest probability, suggesting that rate (or probability) of food delivery influenced the behavioral effects of cocaine.
Asunto(s)
Cocaína/farmacología , Condicionamiento Operante/efectos de los fármacos , Animales , Columbidae , Interpretación Estadística de Datos , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos/fisiología , Alimentos , Refuerzo en PsicologíaRESUMEN
Separate groups of 16 rats received 0, 40, 60, or 80 mg/kg dextromethorphan prior to a 2-h response-acquisition session during which responses on one lever produced food (reinforcement lever, RL, responses) after a 15-s resetting delay and responses on the other lever cancelled food deliveries earned by RL responses, but otherwise had no programmed consequences. When compared to the 0 mg/kg dose, the 40, 60, and 80 mg/kg doses significantly decreased the latency to the tenth RL response, which has been used previously as an index of response acquisition [Pallares, MA, Nadal, RA, Silvestro, JS, Ferre, NS. Effects of ketamine, a noncompetitive NMDA antagonist, on the acquisition of the lever-press response in rats. Physio Behav 1995; 57:389-392.]. Only the 80 mg/kg dose, however, significantly reduced the total number of food pellets earned, the total number of RL responses, or the total number of rats that met the criterion for response acquisition. The present results indicate that dextromethorphan can disrupt initial response acquisition (i.e., learning) with positive reinforcement, although the dose that did so depended on the measure used to index performance. Moreover, the effects of the drug did not appear to reflect specific learning impairment, but rather more general disruption of behavior.
Asunto(s)
Analgésicos Opioides/farmacología , Condicionamiento Operante/efectos de los fármacos , Dextrometorfano/farmacología , Refuerzo en Psicología , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacosRESUMEN
Ten participants from an online community of fiction writers were exposed to a treatment package intended to increase their writing productivity. The package consisted of graphic feedback provided through a Web page, praise for goal completion delivered via e-mail, and editing of manuscripts by other members of the community dependent on the completion of word-count goals. A multiple baseline design across groups was used to evaluate the effects of the intervention, which was successful in increasing the number of words written.
Asunto(s)
Eficiencia , Internet/estadística & datos numéricos , Escritura , HumanosRESUMEN
Pigeons were exposed to a repeated acquisition procedure in which no delays were imposed and rate of responding was relatively high. They also were exposed to conditions in which delays were arranged between trials within chains or between completed chains, and rates of responding were lower. Number of trials, rate of reinforcement, difficulty of the discrimination, and motivating operations were held constant. Terminal accuracy was highest under the no-delay condition, in which rate of responding was highest. Effects of trial spacing on retention were mixed and depended on whether delays were imposed between trials within chains or between completed chains. These findings provide basic-research support for the rapid presentation of trials in direct instruction and for rate building in precision teaching.