RESUMEN
RATIONALE: The cholinergic system is linked extensively to memory, but its exact role remains controversial. In particular, scopolamine-induced impairment in rodents is not task specific, which may be due to difficulty in developing rodent protocols to assess deficits in recent memory, in which the remembered event is brief and distinct, and/or to non-specific behavioral impairment. OBJECTIVES: The present study sought to determine whether scopolamine-induced deficits in recent memory, using a working memory task, could be dose-specifically dissociated from deficits in associative memory in dogs. METHODS: A Latin-square design was used to determine the effect of scopolamine (5, 10 and 15 microg/kg; SC) on a variable delayed-non-matching-to-position (DNMP) task, which assesses visuospatial working memory. Subsequently, the minimal effective dose (15 microg/kg; SC) was administered prior to testing on a landmark discrimination task, which provides a measure of allocentric spatial ability, a black-white discrimination task, an oddity discrimination task and tests of exploratory behavior. We also investigated the effects of a 30 microg/kg dose (SC) on tests of oddity discrimination and behavioral activity. RESULTS: A 15 microg/kg dose produced significant impairment on the DNMP task, but did not affect performance of any discrimination task and did not alter behavior on tests of open field or curiosity. A 30 microg/kg dose caused disruption on discrimination performance and on open field measures. CONCLUSIONS: Working memory performance is most sensitive to scopolamine-induced impairment and can be dissociated from scopolamine-induced deficits in discrimination performance and non-cognitive behaviors. The present results indicate that scopolamine-induced impairments of working memory in the dog can serve as a model of age-related cholinergic dysfunction.
Asunto(s)
Aprendizaje Discriminativo/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Antagonistas Muscarínicos , Escopolamina , Trastornos de la Visión/inducido químicamente , Envejecimiento/psicología , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Femenino , Masculino , Trastornos de la Memoria/psicología , Antagonistas Muscarínicos/administración & dosificación , Recompensa , Escopolamina/administración & dosificación , Trastornos de la Visión/psicologíaRESUMEN
Recent work in our laboratory has investigated and modeled subcellular calcium compartmentation and Ca2+ movement under steady-state control conditions. This experimental study is directed to the further description and quantitation of cellular calcium compartmentation patterns and movements as correlated with contraction in neonatal rat cardiac myocytes in culture under a variety of calcium loading conditions. Compartmental contents were assessed after incubations in various [Ca2+]o, 0 Na+/1 mM Ca2+, and 10 microM ouabain/1.0 mM Ca2+ test solutions. The cellular components investigated include sarcolemmal bound, sarcoplasmic reticulum (SR), and mitochondrial calcium. The results indicate that 1) sarcolemmal calcium binding is insensitive to changes in [Ca2+]o in the range tested (0.25-6.0 mM) while highly sensitive to changes in [Na+]i; 2) SR is sensitive to both changes in [Ca2+]o and [Na+]i and exhibits a maximum loading capacity of approximately 750 micromol Ca2+/kg dw; 3) in the [Ca2+]o range between 0.25 and 2.0 mM, contractile amplitude is proportional to SR content; 4) the mitochondria comprise a high-capacity calcium-containing compartment that is sensitive to changes in [Ca2+]o but does not reach saturation under the conditions tested (0.25-8.0 mM [Ca2+]o); 5) SR calcium is divided into at least two functionally discrete pools, one of which is available for release to the myofilaments during a normal ICa-triggered contraction and other of which is caffeine releasable but unavailable for release to the myofilaments during a normal triggered release; and 6) mitochondrial calcium serves as a reservoir of calcium capable of replenishing and/or augmenting SR stores with anywhere from 10% to 50% of mitochondrial calcium cycling through SR calcium compartments.