Memory-enhancing effects of post-training dipivefrin and epinephrine: involvement of peripheral and central adrenergic receptors

These experiments examined the effects, in mice, of post-training i.p. injections of dipivefrin (DPE), a lipophilic prodrug of epinephrine, and epinephrine (EPI) on 48-h retention assessed in inhibitory avoidance and Y-maze discrimination tasks. DPE, in doses of 0.3-10 micrograms/kg significantly facilitated retention: the effects were approximately 10-fold more potent than those of EPI obtained with similar experimental conditions. The alpha-adrenergic antagonists prazosin (alpha 1; 3.0 mg/kg; i.p.), yohimbine (alpha 2; 3.0 mg/kg; i.p.) and phentolamine (alpha 1 and alpha 2; 3.0 mg/kg; i.p.) did not block the enhancement of retention induced by either DPE (10.0 micrograms/kg; i.p.) or EPI (0.1 mg/kg; i.p.). However, the beta-adrenergic antagonist propranolol (2.0 mg/kg; i.p.) attenuated the effects of both DPE and EPI. Sotalol (2.0 mg/kg; i.p.), a peripherally-acting beta-adrenergic antagonist, attenuated the effects of EPI but not those of DPE. These findings suggest the DPE-induced enhancement of memory involves central beta- but not alpha-adrenergic mechanisms while EPI's effects are initiated by activation of peripheral beta-adrenergic systems.