Concurrent blockade of beta-adrenergic and muscarinic receptors disrupts working memory but not reference memory in rats.

In order to clarify the interactions between monoaminergic and cholinergic systems in working and reference memory functions, the effects of administration of the alpha, beta-adrenergic, D1-, D2-dopaminergic or serotonergic receptor antagonist together with the muscarinic receptor antagonist scopolamine on this behavior were examined using a three-panel runway task. Both in working and reference memory tasks, the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) was significantly increased by 0.32 mg/kg scopolamine, but not by the doses up to 0.18 mg/kg. The beta-adrenergic antagonist propranolol at 10 mg/kg had no effect on the number of working memory errors. Combined administration of 10 mg/kg propranolol and scopolamine at 0.1 and 0.18 mg/kg significantly increased the number of working memory errors. However, in a reference memory task, propranolol at 10 mg/kg did not affect the number of errors, whether administered alone or together with 0.1 mg/kg scopolamine. Other monoaminergic receptor antagonists, including the alpha-adrenergic antagonist phentolamine (3.2 and 10 mg/kg), D1-antagonist SCH23390 (0.032 and 0.056 mg/kg). D2-antagonist sulpiride (100 mg/kg) and serotonin antagonist cinanserin (10 and 32 mg/kg) had no significant effect on working or reference memory errors, whether they were administered independently or in combination with scopolamine at 0.1 mg/kg. These results suggest that beta-adrenergic/muscarinic interactions play an important role in mediating processes involved in working memory performance of rats.