Water maze impairments after combined depletion of somatostatin and serotonin in the rat

This study examined the effect of both separate and combined depletion of brain somatostatin and serotonin on acquisition of the water maze (WM) task. Naive male Long-Evans rats received injections of p-chlorophenylalanine (PCPA; 500 mg/kg x 2) to deplete serotonin or cysteamine (90 or 200mg/kg) to deplete somatostatin, or both treatments prior to spatial and reversal training in the water maze. Some rats first received Morris' nonspatial pretraining to train them in the behavioral strategies that are required for successful spatial place learning in this task, prior to drug treatment and spatial training. A detailed behavioral analysis indicated that somatostatin or serotonin depletion alone caused little or no impairment in naive animals. Depletion of both somatostatin and serotonin in naive rats impaired performance, with differences in the impairments that depended on the dose of cysteamine. Nonspatially pretrained rats were not impaired. Thus, neither somatostatin nor serotonin alone is crucial or the water maze task, but impairments occur if both somatostatin and serotonin are depleted in naive rats. The results indicate that some of the performance impairment was due to strategies impairment rather than a spatial place learning impairment. Depletion of both somatostatin and serotonin in naive rats produces results comparable to the spatial navigation deficits seen in some Alzheimer patients and suggests that combinations of antagonist treatments may better model this disorder than single antagonist treatments do. (c) 2007 Elsevier B.V. All rights reserved.