Therapeutic effects of levothyroxine in a rat model of scopolamine-induced cognitive impairment: An electrophysiological, behavioral, and biochemical study

Scopolamine (SCOP), an anticholinergic drug, is commonly used for inducing a cognitive deficiency in experimental animal models. Ninety six Wistar male rats were divided into six groups [Control, Control + Levothyroxine (L-T4, 100), SCOP + Vehicle, SCOP + L-T4 (50 and 100), SCOP + donepezil (DP)]. During 21 consecutive days, SCOP (1 mg/kg, i.p.) was used with the purpose of inducing an animal model of cognitive impairment. Thirty min after the administration of SCOP, animals were treated with 50 and 100 mg/kg L-T4, 3 mg/kg of DP, or normal saline for 21 days. The behavioral (passive avoidance and spatial memory, anxiety, depression, locomotion, and motor coordination), and electrophysiological (hippocampal long-term potentiation (LTP)) assessments, as well as biochemical changes, were estimated. Results indicated that the indices of depression/anxiety, spatial/passive avoidance memory, motor coordination, LTP records (amplitude and slope), and antioxidant enzyme activity were significantly decreased in SCOP groups in comparison with the control. Compared to the control group, L-T4 (50 and 100 mg/kg) treated rats showed significant improvements in memory and learning deficits, anxiety, all LTP parameters, and the antioxidant enzyme concentrations. The cerebral contents of tumor necrosis factor-alpha (TNF-α) in the L-T4 and DP treated groups were significantly lower than that of the SCOP + Veh group (p < 0.01). This research showed that the L-T4 prevented the disruption of synaptic plasticity and cognitive deficiencies induced by SCOP. The beneficial effects of L-T4 may be due to a decrease in the concentration of TNF-α and enhancement of the antioxidant content in the hippocampus.