Nimodipine facilitates retention of the classically conditioned nictitating membrane response in aged rabbits over long retention intervals.

Aged rabbits initially underwent 18 days of acquisition of the classically conditioned nictitating membrane response (NMR) using a tone conditioned stimulus (CS) and an air puff unconditioned stimulus (UCS). They were then treated with a low or high dose of nimodipine or a vehicle for 90 days. During this time no further CS-UCS pairings were presented. They underwent testing for retention of the conditioned response (CR) at 30 and 90 days. Retention testing consisted of 20 presentations of the CS alone. Rabbits in the control condition retained 46.4% of their predrug levels of conditioned responding and rabbits receiving the low dose of nimodipine retained 37.3% of their predrug levels after 30 days. After 90 days, retention in these animals declined to 8.1% and 14.1%, respectively. In contrast, rabbits receiving the high dose of nimodipine retained 85% of their predrug learning at 30 days with little decline at 90 days (77.1%). Nonassociative factors such as sensitivity to the CS or UCS could not explain these effects.

Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

Disruption of human eyeblink conditioning after central cholinergic blockade with scopolamine.

Human (Homo sapiens) volunteers (N = 72) received saline, a low dose of oral scopolamine (0.6 mg), a high dose of oral scopolamine (1.2 mg), or a peripheral analogue (glycopyrrolate). They then underwent classical conditioning of the eyeblink response to a tone conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS) in a delay conditioning paradigm. There was a dose-related decline in acquisition of the conditioned response. These drug-induced conditioning deficits were similar to those previously reported in rabbit eyeblink conditioning and could not be attributed to such nonassociative factors as changes in auditory thresholds to the tone CS, magnitude of reflexive blinks to the airpuff UCS, or to changes in spontaneous blink rates.

Classical conditioning in patients with Alzheimer's disease: a multiday study.

Previous studies demonstrated that patients with Alzheimer's disease (AD) do not acquire the classically conditioned eyeblink response. These studies, however, were only tested over a single conditioning session and, hence, raise the question of whether AD patients are capable of acquiring the response if sufficient training is given. This question may be of some importance whether AD patients can ultimately acquire the response has implications for the underlying neurobiological deficit in disrupted conditioning in AD. This study tested AD patients and age-matched controls over 4 days. As in previous studies, AD patients performed significantly worse than controls on Day 1, but by Day 4, they were not significantly different from controls. Subsequent testing indicated that these effects were not due to nonassociative variables such as changes in sensitivity to stimuli or disruption of the motor response. Also, it was reported that neither AD patients nor controls showed any evidence of acquisition in an explicitly unpaired paradigm, suggesting that neither pseudoconditioning nor sensitization is contributory. Data are discussed in terms of the possible role of the hippocampus in mediating conditioning deficits in AD patients.