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

Abstract 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 μg/kg significantly facilitated retention: the effects were approximately 10-fold more potent than those of EPI obtained with similar experimental conditions. The α-adrenergic antagonists prazosin (α 1 ; 3.0 mg/kg; i.p.), yohimbine (α 2 ; 3.0 mg/kg; i.p.) and phentolamine (α 1 andα 2 ; 3.0 mg/kg; i.p.) did not block the enhancement of retention induced by either DPE (10.0 μg/kg; i.p.) or EPI (0.1 mg/kg; i.p.). However, the β-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 β-adrenergic antagonist, attebuated the effects of EPI but not those DPE. These findings suggest the DPE-induced enhancement of memory involves central β- but not α-adrenergic mechanisms while EPI's effects are initiated by activation of peripheral β-adrenergic systems.