Temporally Graded Retrograde Amnesia of Contextual Fear after Hippocampal Damage in Rats: Within-Subjects Examination

Five experiments studied retrograde impairments in Pavlovian fear conditioning following prolonged exposure to the opioid receptor agonist morphine. Injections of morphine commencing 1-7 days but not 14 days after conditioning produced amnesia for that conditioning episode. This amnesia was (a) selective such that morphine impaired freezing to the conditioning context but not to the auditory conditioned stimulus, (b) independent of the interval between the last injection of morphine and test, and (c) accompanied by a failure of contextual discrimination. Context preexposure protected context conditioning and discrimination from the amnestic effects of morphine. These results show that retrograde deficits in contextual fear conditioning are mediated by failures to consolidate a contextual representation.

Rationale and Objectives-With prescriptions of stimulants on the rise, it is important to examine the cognitive effects of low and moderate doses of stimulants, rather than only those typical of addicts.Methods-The present study examined the effects a range of doses (0.005 -8 mg/kg) of damphetamine sulfate on cued and contextual Pavlovian fear conditioning in mice.Results-In agreement with previous research, subjects administered a moderately high dose of amphetamine (8 mg/kg) pre-training, typical of what addicts might take, displayed impaired memory when tested, off-drug. Alternately, subjects injected with a very low dose of amphetamine (0.005, 0.025, or 0.05 mg/kg), pre-training, similar to the therapeutic doses for attention deficit hyperactivity disorder, displayed enhanced memory when tested, off-drug. A control study showed these effects were not due to state-dependent learning.Conclusions-Thus, dose is a critical determinant of the cognitive effects of psychostimulants.

Muscarinic-cholinergic antagonism produces learning and memory deficits in a wide