Differential effects of scopolamine and mecamylamine on working and reference memory in the rat

The effects of the muscarinic antagonist scopolamine (0.1-0.6 mg/kg, IP) and the nicotinic antagonist mecamylamine (1-10 mg/kg) were compared in T-maze alternation and discrimination tasks in the rat. Scopolamine dose dependently disrupted performance on the alternation task and potentiated the increase in errors made in controls when the delay between forced and choice runs was increased from 0 to 30 s. Mecamylamine disrupted performance at the 10-mg/kg dose only and dose dependently inhibited the increase in errors made in controls when the delay between forced and choice runs was increased to 30 s. In simple T-maze discrimination, only the 0.6-mg/kg dose of scopolamine disrupted performance of the task, while mecamylamine at both 5 and 10 mg/kg disrupted task performance. These results confirm that working memory tasks are more sensitive to central muscarinic blockade than reference memory tasks. They also demonstrate that in delay conditions working memory performance is enhanced following central nicotinic blockade while reference memory performance is disrupted. This suggests that centrally active muscarinic and nicotinic antagonists have dissociable effects on memory processes in the rat.