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

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In order to clarify the interactions between monoaminergic and cholinergic systems in working and reference memory functions, the effects of administration of the α, β-adrenergic, D 1-, D 2-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 β-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 α-adrenergic antagonist phentolamine (3.2 and 10 mg/kg), D 1-antagonist SCH23390 (0.032 and 0.056 mg/kg), D 2-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 β-adrenergic/muscarinic interactions play an important role in mediating processes involved in working memory performance of rats.