Effects of Rimonabant on learning and memory of rats with olfactory bulbectomy

Abstract

Olfactory bulbectomy (OBX) is an experimental model of depression, which has recently been used as a model of Alzheimer's disease due to the development of neurodegenerative changes in the brain. The OBX model in rodents is accompanied by biochemical, morphological and structural changes in the brain, as well as by many behavioral changes. A common finding in the OBX model are memory deficits, which are present in both depressive disorders and neurodegenerative diseases. There is evidence that the memory-impairing effect of cannabinoids is associated with activation of the cannabinoid CB1 receptors in the brain. The aim of the present study was to investigate the effects of the CB1 antagonist Rimonabant (SR 141716A) administered intragastrically daily for 14 days on the memory processes of OBX rats, tested in a passive avoidance (PA) paradigm. Rimonabant was administered to OBX rats, divided into three experimental groups: before OBX; immediately after OBX (1-14 days); with the presence of a depressive-like state (14-28 days after OBX). Rimonabant showed a tendency to improve the learning and memory of sham-operated controls, whereas no significant change in the behavioral responses was observed upon administration 14 days before OBX. However, Rimonabant, administered immediately after OBX completely prevented the development of memory deficit in a PA test, while its administration 14-28 days after OBX ameliorated the memory disturbances induced by bulbectomy. The results indicate that the CB1 antagonist Rimonabant may ameliorate the development of a memory deficit in OBX rats.