Multiple injections of thyrotropin releasing hormone fail to reverse learning and memory deficits in rats with lesions of the nucleus basalis of meynert

The learning and memory enhancing effects of thyrotropin releasing hormone (TRH) was examined in an animal model of Alzheimer's disease. Adult rats were prepared with either sham surgeries or cholinergic lesions of the nucleus basalis of Meynert (nbM). Subjects were injected (ip) with one of three doses of TRH (0, 5, 10 mg/kg) starting on the day of surgery and continuing once every other day for a total of four injections. Performance (four trials/day for 4 days, 30 in inter-trial interval) in a Morris water maze was assessed one week after the last TRH injection (i.e., 2 weeks postoperatively). Latency to find the hidden platform served as the dependent variable. Results indicated that damage to the nbM impaired task performance in that animals with nbM lesions generally required more time to find the platform and showed less trial-to-trial improvement. Treatment with TRH failed to reverse this lesion-induced deficit. These results suggest that multiple injections of TRH do not provide residual protection against the deleterious effects on learning and memory produced by cholinergic lesions of the basal forebrain. Other doses and administration parameters, however, need to be studied in order to determine the generalizability of these findings. (C) 2002 Elsevier Science B.V. All rights reserved.