Modulation of memory by post-training epinephrine: involvement of cholinergic mechanisms

Extensive evidence indicates that memory storage can be modulated by peripheral epinephrine as well as by drugs affecting the muscarinic cholinergic system. Low doses of epinephrine (Epi) facilitate memory while high doses induce amnesia. Retention is enhanced by post-training administration of cholinergic muscarinic agonists and impaired by antagonists. The present experiments examined the interaction of peripheral Epi and cholinergic drugs in memory modulation. Male CFW mice (60 days old) were trained on an inhibitory avoidance response (IA) or a Y-maze discrimination response (YMD), injected (IP) immediately post-training and tested 24 h later. In the Y-maze task, retention was assessed by discrimination reversal training. Findings obtained in the two tasks were comparable. Epi (IA: 3.0 micrograms/kg; YMD: 30.0 micrograms/kg) potentiated the memory-enhancing effect of low doses of oxotremorine (Otm) (IA: 16; YMD: 5.0 micrograms/kg) and physostigmine (Phy) (6.8 and 22.0 micrograms/kg for both IA and YMD). The memory-facilitating effect of Otm (50.0 micrograms/kg) was not blocked by an amnestic dose of Epi (IAT: 0.3 mg/kg; YMD: 1.0 mg/kg). Retention was not affected when these amnestic doses of Epi were administered together with a memory-facilitating dose of Phy (68.0 micrograms/kg). In contrast, atropine (IA: 10.0 mg/kg; YMD: 3.0 mg/kg) completely blocked the facilitatory effect of Epi (IA: 10.0 micrograms/kg; YMD: 300 micrograms/kg). These findings indicate that, when administered in low doses, Epi interacts with Otm and Phy. However, cholinergic drugs can block both the memory-enhancing and the memory-impairing effects of Epi. The findings suggest that Epi may modulate memory through cholinergic systems.