Retrograde amnesia: Lack of attenuation with centrally administered adrenergic antagonists

Previous results indicate that pretraining peripheral injections of any of several adrenergic receptor antagonists can attenuate retrograde amnesia. The present experiment was an attempt to determine whether the attenuation of amnesia was due to peripheral or central actions of the adrenergic antagonists. This experiment examined the effects of intracerebroventricular (ICV) injections of these antagonists on the amnesia produced by supraseizure electrical stimulation of frontal cortex. Thirty minutes prior to training, rats received an ICV injection of an α-adrenergic (phenoxybenzamine, phentolamine, or piperoxane) or a β-adrenergic antagonist (propranolol) through a cannula in the lateral ventricle. After one-trial inhibitory (passive) avoidance training, the animals received stimulation of frontal cortex at an intensity that produces brain seizures and amnesia. The antagonists did not, in general, attenuate the amnesia produced by frontal cortex stimulation. One drug, propranolol, did attenuate the amnesia but this agent also impaired the brain seizure itself. Thus, the results suggest that adrenergic antagonists act to block the production of retrograde amnesia by interfering with peripheral aminergic responses to memory-impairing treatments.