George A. Heise

Central cholinergic involvement in working memory: Effects of scopolamine on continuous nonmatching and discrimination performance in the rat.

Rats were trained to stable baselines of lever pressing on a variable intertrial interval continuous nonmatching to sample schedule (CNM) or on an analogous discrimination schedule. Scopolamine reduced accuracy of CNM performance to a similar extent over the three intertrial (retention) intervals: 2.5, 5, and 10 s, results indicating that the drug did not affect the time-dependent process of retention in working memory. When baseline levels of performance accuracy were similar in the CNM and discrimination tasks (but stimulus discriminability was greater in the CNM task), scopolamine reduced accuracy equally in the two procedures. Effects of scopolamine on accuracy of noncorrection trial CNM performance were simulated by reducing stimulus discriminability; however, scopolamine disrupted CNM correction trial performance much more than did reductions in stimulus discriminability. It is concluded that scopolamines effects on working memory are not limited to possible effects on stimulus discrimination: Scopolamine may also affect retrieval of response rules from reference memory.

Effects of scopolamine on variable intertrial interval spatial alternation and memory in the rat.

A repeated measures procedure, variable intertrial interval (ITI) spatial alternation, was used to assess scopolamine effects on memory, and to compare effects of the drug on discrimination processes with effects on storage. Rats learned in two stages to press left and right levers in alternation on discrete trials separated by 5 different ITIs ranging from 2.5 to 40 s and presented in random order during the experimental session. In the first stage, alternating discrimination, alternation was controlled by a light on over the correct lever at the time of the trial; in the second stage, variable ITI spatial alternation, a centrally located panel light signalled all trials and alternation was controlled by stimuli from prior trials (‘memory’). Alternation response occurrence declined moderately (but significantly) with increasing ITI duration in both the alternating discrimination and variable ITI spatial alternation stages; response occurrence was also significantly decreased by scopolamine treatment in both stages. Accuracy of alternating discrimination performance was not significantly altered by either ITI duration or scopolamine treatment. Accuracy of variable ITI spatial alternation performance on a trial varied inversely with the duration of the ITI that preceded the trial. Scopolamine treatment significantly reduced accuracy of lever pressing in variable ITI spatial alternation but did not alter the slope of the curves relating accuracy to ITI duration. These effects indicate that the drug impaired discrimination processes but did not alter memory storage.

Effects of scopolamine on components of delayed response performance in the rat

The effects of scopolamine and methyl scopolamine on working memory processes were investigated in a paired trial, go-no go delayed response procedure in which rats initiated their own trials. Drug effects were examined concurrently on performance at three delays--no, 0, and 2.5 sec. Scopolamine disrupted no-delay (discrimination) performance in a dose-related manner. Scopolamine also progressively reduced performance at 0-delay and 2.5 sec delay more than at no-delay, but only at the highest administered dose (0.5 mg/kg). Scopolamine affected sensitivity, but not response bias. Although both scopolamine and methyl scopolamine reduced the probability of trial initiation, only scopolamine disrupted accuracy of performance on the initiated trials.

Effects of scopolamine, atropine, and d-amphetamine on internal and external control of responding on non-reinforced trials.

Rats learned not to respond on non-reinforced trials in a discrete trial situation in which trial responses were reinforced only if preceded by three or more non-response trials. Drug effects were measured: 1) when the same external stimuli were present on all trials and trial responding was therefore controlled by events that occurred prior to the trial (“internal control”); and 2) when the external stimuli on trials on which responding was reinforced were different from the external stimuli present on trials on which responding was not reinforced (“external control”). Scopolamine impaired performance (i.e. reduced the percentage of trial responses that were reinforced) to about the same extent under the internal and external control conditions. d-Amphetamine, on the other hand, impaired nonresponding on trials only under internal control conditions. Atropine affected both internally and externally controlled non-responding but had a greater effect on internally controlled non-responding.

Effects of pesticides and drugs on working memory in rats: Continuous delayed response

Effects of four pesticides (carbaryl, propoxur, chlordimeform, and deltamethrin) and four reference drugs (physostigmine, scopolamine, methscopolamine, and chlordiazepoxide) were measured in two delayed response, working memory procedures: go-no go alternation in which rats initiated their own trials, and spatial reversals. Four of these compounds (carbaryl, propoxur, physostigmine, and scopolamine) were also tested in a go-no go alternation procedure in which animals did not initiate their trials. The pesticides and physostigmine did not selectively affect working memory in any of the procedures: low doses only moderately decreased response accuracy, whereas higher doses suppressed responding indiscriminately. The pesticides and physostigmine had similar effects on go-no go alternation (i.e., working memory) and analogous go-no go discrimination performance. Effects on go-no go alternation performance did not depend on whether the animals initiated their own trials. Scopolamine, in contrast, appeared to disrupt working memory. It profoundly disrupted accuracy at doses that only moderately decreased over-all responding and impaired go-no go alternation accuracy much more than discrimination accuracy.

Effects of pesticides and drugs on working memory in rats: Continuous non-match

Effects of four pesticides (carbaryl, propoxur, chlordimeform, and deltamethrin) and two reference drugs, physostigmine and chlordiazepoxide, were measured on the performance of rats trained on a continuous non-match (CNM) delayed comparison, working memory procedure. These same compounds were also tested in analogous, large and small stimulus difference discrimination (i.e., non working-memory) procedures. The effects of the pesticides and physostigmine on CNM performance were qualitatively similar, and also similar to their effects on discrimination performance. As dosage of these compounds increased, only small effects on accuracy were observed, followed at still larger doses by an abrupt and non-selective decrease in all responding. The pesticides and physostigmine did not selectively affect working memory: the magnitude of their effects did not increase with intertrial interval, and the compounds were equally effective in disrupting discrimination and CNM performance. Effects of chlordiazepoxide on performance in the CNM and discrimination control procedures differed qualitatively from those of the pesticides and physostigmine.

Effects of physostigmine on operant serial discrimination/reversal learning in rats☆

Two experiments examined the effects of physostigmine on acquisition and performance of operant serial reversals by rats. In Experiment 1, four groups of rats (n = 6/group) were injected with either vehicle or 0.03 mg/kg physostigmine five minutes prior to each session, or vehicle or 0.5 mg/kg physostigmine immediately after each session of a three-stimulus (bright, dim or flashing light) repeated discrimination/reversal procedure. Rats treated with physostigmine pre- or postsession learned significantly more reversals over 50 sessions than animals injected with vehicle. Experiment 2 used only two discriminative stimuli, a light and a 2,500 Hz tone. Following establishment of a stable daily reversal baseline, postsession injections of physostigmine significantly increased the number of trials to criterion on the next session compared to each subjects control baseline. Results are attributed to enhanced between-session transfer of previously learned discriminated instrumental responses by physostigmine-treated animals.

Failure of TCAP to facilitate acquisition of double alternation in rats

Abstract Acute injections of tricyanoaminopropene (TCAP) given to adult rats prior to and during training did not affect the rate of acquisition of a go, no-go double alternation sequence. In a second experiment, TCAP was chronically administered to rats commencing prior to parturition. When tested as adults, these rats performed significantly more poorly than a rearing control group on some double alternation acquisition sessions. A third experiment showed that TCAP administration to adult rats did not increase response rates on a continuous avoidance task.