Timothy F. Elsmore

SYNWORK1: A PC-based tool for assessment of performance in a simulated work environment

SYNWORK1 is a computer-based performance task that requires subjects to work simultaneously on four distinct subtasks involving memory, arithmetic processing, and visual and auditory monitoring. Difficulty levels, the payoff matrix, feedback levels, and component subtask mix are user selectable. Detailed data are automatically collected, and a suite of data analysis programs is available. SYNWORK1 is being used in sleep-deprivation and circadian desynchronization experiments and in a variety of clinical research applications. Representative data from a sleep-deprivation experiment are presented to demonstrate the sensitivity of the technique. The strategy used for programming concurrent tasks on a PC is described.

Inhibition of Normal Growth by Chronic Administration of Δ-9-Tetrahydrocannabinol

Body weight, food and water intake, and feces weight of 20 albino rats were recorded daily for 70 days. On days 11 to 40, 12 rats received behaviorally effective doses of Δ-9-tetrahydrocannabinol, either orally or intraperitoneally. These rats ate significantly less than placebo-dosed controls during the treatment period, and gained significantly less weight. Food intake recovered in the 30-day posttreatment period, but the former drug group still weighed less than the controls on day 70. In addition, all rats who had received intraperitoneal injections of Δ-9-tetrahydrocannabinol showed evidence of chronic diffuse nonsuppurative peritonitis.

Reduction of heroin intake in baboons by an economic constraint

Baboons earned their total food ration in a situation where they were periodically given an opportunity to choose between food and an intravenous infusion of heroin. As the number of daily choices was restricted, food intake remained relatively constant, while heroin intake decreased dramatically.

Δ9-Tetrahydrocannabinol: Dose-Related Effects on Timing Behavior in Chimpanzee

Δ9-Tetrahydrocannabinol, at doses within the effective range for humans, was administered orally to chimpanzees with stable, efficient timing performances maintained by multilink chained schedules of food reinforcement. Reinforcements decreased with increasing dose, because of decreased frequencies of total operant timing responses and decreased accuracy of the timing performances which did occur. Higher doses exerted an effect for up to 3 days.

Effects of delta-9-tetrahydrocannabinol on temporal and auditory discrimination performances of monkeys

In two experiments, macaques were trained to respond differentially to either the duration of a visual stimulus or to the frequency of an auditory clicker. In the duration discrimination experiment, delta-9-tetrahydrocannabinol (delta-9-THC) was administered acutely in doses from 1 to 16 mg/kg, producing dose-related decrements in accuracy of the discrimination performance, and a reduction in the rate at which the animals initiated discrimination trials. In both the duration and auditory discrimination experiments, chronic daily administrations of 2 to 16 mg/kg of delta-9-THC produced an initial decrement in accuracy and rate of trial initiation. Both measures showed some development of tolerance, tending to return to baseline levels, however, the time course of tolerance was different for the measures, with the rate of trial initiation recovering more quickly than accuracy. No differences in response to the drug were attributable to the different modalities used in these two experiments.

Environmental influences on the development of tolerance to the effects of physostigmine on schedule-controlled behavior

The influence of environmental variables on the development of tolerance to physostigmines effects in rats was examined using multiple fixed-ratio, extinction schedules of food presentation. Initial administration of physostigmine (0.4 mg/kg) produced nearly maximal decreases in the number of food pellets delivered, running response rate, and overall response rate, under multiple FR 10, EXT and multiple FR 50, EXT schedules. With repeated administration, tolerance to physostigmines effects was observed when 10 responses were required to produce reinforcement but was not observed when 50 responses were required to produce reinforcement. Tolerance under the multiple FR 10, EXT schedule of reinforcement was also observed when physostigmine was administered post-session. When tolerance was acquired, it was retained for up to 25 drug-free days. These results suggest that tolerance to physostigmines effects on schedule-controlled behavior is strongly influenced by response requirement, independent of physostigmine-induced reinforcement loss. Additionally, tolerance is not dependent on experience with the schedule while under the effects of physostigmine, and is retained for a substantial period of time in the absence of continued physostigmine administration.

Shock-elicited fighting and delta-9-tetrahydrocannabinol.

The frequency with which electric shock to the feet elicited fighting in five pairs of albino rats was not altered significantly by intraperitoneal injections of delta-9-tetrahydrocannabinol (THC) in doses ranging from 0.064–6.4 mg/kg, although chlordiazepoxide reduced the frequency of such fighting in a dose-related manner. This finding held true despite manipulations of THC vehicle, injection-test interval, and the previous drug experience of the subjects. In contrast, doses of 4.0 mg/kg produced a striking reduction in lever-pressing maintained by an FI 60″ schedule of food reinforcement.

Relationship of the behavioral effects of aprophen, atropine and scopolamine to antagonism of the behavioral effects of physostigmine

Behavioral effects of aprophen, atropine and scopolamine, in rats, were examined under a multiple schedule of food presentation and at different injection-test times. The effects of the varied treatments were compared to the ability of the drugs, under identical conditions, to prevent the behavioral effects of the anticholinesterase, physostigmine. Potencies of the antagonists to decrease response rates varied across three log units. All three antagonists produced dose-related attenuation of the response suppressant effects of physostigmine. In general, aprophen was a better antagonist than scopolamine or atropine. It blocked behavioral effects of physostigmine across a wider range of doses than the other compounds, and did so with less behavioral disruption. Although substantial differences between the three antagonists were observed, the behavioral effects of all three antagonists (when administered alone) were positively correlated with their efficacy as antagonists of the response suppressant effects of physostigmine.

Reduction of predatory aggression of rats following administration of delta-9-tetrahydrocannabinol

Abstract Twenty rats were individually tested for the occurence of an attack upon a turtle 1, 2, 4, and 8 hours after intraperitoneal injections of either placebo or a 6.4 mg/kg dose of Δ:9-tetrahydrocannabinol. In comparison to days when the rat received placebo injections, the percentage of attacks at 1 and 2 hours post-injection was significantly less on days when the Δ:9-THC was administered, while at 4 and 8 hours post-injection there was no significant difference between the percentage of attacks on either drug or placebo days. The data support previous research that shows that under certain conditions Δ:9-THC has the effect of reducing aggressive behavior.

Central vs peripheral anticholinergic effects on repeated acquisition of behavioral chains

Monkeys that were required to repeatedly learn new sequences of responses to obtain food were injected with 0.2 mg/kg of atropine sulfate or methylatropine nitrate. Effects lasted 8 to 12 hr following injection. Both drugs decreased the rate at which the animals worked, but only atropine sulfate increased the number of attempts required to solve the problem and decreased overall accuracy, suggesting a peripheral mode of action for rate-decreasing effects, and a central mode of action for effects of atropine on qualitative aspects of performance.