RESUMEN
Galanin (GAL) impairs performance on cognitive tasks when administered centrally to rats. GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits on the probe trial of the Morris water maze spatial learning task, on the social transmission of food preference olfactory memory task, and on the trace cued fear conditioning emotional learning and memory task. Knockout mice deficient in the GAL-R1 receptor subtype were normal on most memory tasks, while showing a small deficit in trace cued fear conditioning, suggesting a selective role for the GAL-R1 in aversive memories, and implicating other GAL receptor subtypes in spatial learning and olfactory social memory. The growing body of rodent literature implicating excess GAL in cognitive impairment is relevant to the overexpression of GAL in the basal forebrain during the progression of Alzheimer's disease.
Asunto(s)
Trastornos del Conocimiento/fisiopatología , Galanina/genética , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Receptor de Galanina Tipo 1/genética , Animales , Galanina/metabolismo , Ratones , Ratones Noqueados , Ratones Transgénicos , Receptor de Galanina Tipo 1/metabolismoRESUMEN
The neuropeptide galanin induces performance deficits in a wide range of cognitive tasks in rodents. Three G-protein-coupled galanin receptor subtypes, designated GAL-R1, GAL-R2 and GAL-R3, have been cloned. The present study examined the role of GAL-R1 in cognition by testing mice with a null mutation in Galr1 on several different types of learning and memory tasks. Assessments of general health, neurological reflexes, sensory abilities and motor functions were conducted as control measures. Mutant mice were unimpaired in social transmission of food preference and the Morris water maze. In tests of fear conditioning, mutant mice were unimpaired in a delay version of cued fear conditioning. However, mice homozygous for the null mutation were impaired in a trace version of cued fear conditioning. Mutant mice were unimpaired in contextual fear conditioning, whether training was by the delay or trace protocol. General health, neurological reflexes, sensory abilities and motor functions did not differ across genotypes, indicating that the trace fear conditioning deficit was not an artifact of procedural disabilities. The findings of normal performance on several cognitive tasks and a selective deficit in trace cued fear conditioning in homozygous GAL-R1 mutant mice are discussed in terms of hypothesized roles of the GAL-R1 subtype. The generally normal phenotype of GAL-R1 null mutants supports the use of this line for identification of the receptor subtypes that mediate the cognitive deficits produced by exogenous galanin.
Asunto(s)
Memoria/fisiología , Receptor de Galanina Tipo 1/deficiencia , Animales , Condicionamiento Psicológico/fisiología , Femenino , Aprendizaje/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Desempeño Psicomotor/fisiología , Receptor de Galanina Tipo 1/genéticaRESUMEN
Galanin is a neuropeptide that inhibits the evoked release of several neurotransmitters, inhibits the activation of intracellular second messengers, and produces deficits in a variety of rodent learning and memory tasks. To evaluate the actions of galanin on encoding, consolidation, and storage/retrieval, galanin was acutely administered to Sprague-Dawley rats at time points before and after training trials in the Morris water maze. Intraventricular administration of galanin up to 3h after subjects had completed daily training trials in the Morris water task impaired performance on the probe trial, indicating that galanin-blocked consolidation. Pretreatment with an adenylate cyclase activator, forskolin, prevented the deficits in distal cue learning produced by galanin. Di-deoxyforskolin, an inactive analog of forskolin, had no effect. These results provide the first evidence that galanin interferes with long-term memory consolidation processes. A potential mechanism by which galanin produces this impairment may involve the inhibition of adenylate cyclase activity, leading to inhibition of downstream molecular events that are necessary for consolidation of long-term memory.
Asunto(s)
Galanina/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Retención en Psicología/efectos de los fármacos , Adenilil Ciclasas/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Colforsina/farmacología , Inyecciones Intraventriculares , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , AguaRESUMEN
Galanin inhibits the release of several neurotransmitters and produces performance deficits in a variety of spatial and aversive learning and memory tasks. The experiments in this study investigated the role galanin has in emotional learning and memory using a standard delay cued and contextual fear conditioning task. Rats were administered galanin into the lateral ventricles before training, and scored for freezing behavior in the same context and in a novel context with and without an auditory cue (CS) that had been paired previously with an aversive stimulus (US). Galanin-overexpressing transgenic mice were tested in an identical behavioral protocol. The galanin-administered rats and the transgenic mice were not significantly different from their respective controls on this task. A more challenging trace cued and contextual fear conditioning procedure was administered to separate groups of galanin-treated rats and galanin-overexpressing transgenic mice. Subjects were trained with the same CS and US, however, a 2.5-sec delay was inserted between CS offset and US onset. Following the trace conditioning, rats administered galanin and mice overexpressing galanin both exhibited significantly less freezing to the CS in the novel context as compared with their control groups. These results indicate that the observed disruption of cued fear conditioning was specific to the more difficult trace conditioning task. These findings are the first demonstration that galanin impairs performance on an emotional memory task and support the hypothesis that galanin-induced deficits are specific to more difficult cognitive tasks.