Oakley S. Ray

Brain stimulation reward „Thresholds” self-determined in rat

SummaryThe self-stimulation technique of Olds is modified to permit a continuous determination of the smallest current levels that will produce a rewarding effect by stimulating positive brain sites. The animal receives brief brain shocks that decrease in intensity in small steps by operating one lever, and indicates which current step stimulated insufficiently by resetting the current at a second lever. Preliminary data suggest that the technique will provide a valuable tool for the investigation of the central nervous system actions of drugs.

Behavioral, pharmacological, and biochemical analysis of genetic differences in rats

Several strains of commercially available rats were studied which showed clear behavioral differences in activity and in shock avoidance behavior. Intensive study of two behaviorally very different strains, F-344 and Zivic-Miller, shows that their differences in shuttle box avoidance acquisition is genetic and is based on their activity response to shock stress rather than to a difference in general learning ability. Drug administration and lesion studies suggested that the behavioral differences were due to differences in brain monoamine responses to shock stress. Biochemical studies of brain serotonin, norepinephrine, and dopamine turnover following stress support this concept.

Reinforcement Magnitude as a Determinant of Performance Decrement after Electroconvulsive Shock

The intensity of a foot shock may be a determinant of the rate at which an avoidance response becomes resistant to disruption by electroconvulsive shock. Mice were trained, one trial a day, in a passive avoidance learning task, with one of three foot-shock intensities. Electroconvulsive shock was administered at various intervals after each trial. At all foot-shock intensities, electroconvulsive shock given 10 seconds after each training trial was eflective in disrupting learning. Where electroconvulsive shock was given at longer intervals after each trial, those animals learning at low intensities of foot shock showed greater impairment of performance than those learning at high intensities.

An analysis of the facilitation of avoidance acquisition produced by d-amphetamine and scopolamine

Albino rats from an inbred strain (F344s) and a random bred Sprague-Dawley derivative (ZMs) were administered intraperitoneal injections of either saline, 1.0 mg/kg d -amphetamine, 0.6 mg/kg scopolamine, or a combination of both drugs (0.5 mg/kg d -amphetamine plus 0.3 mg/kg scopolamine) 30 min prior to daily sessions of 25 trials on a brightness discrimination, active-avoidance task in completely automated Y-mazes. For the ZMs, all drug treatments significantly facilitated acquisition of the avoidance response. This facilitation was due to increase in active responses (incorrect avoidances, intertrial crosses, intertrial motor activity) which provided a behavioral baseline which was compatible with learning the requirements of the task. The major effect of the drugs on the F344s, who normally avoid well, was a disruption of behavior in the Combination group, indicating the importance of assessing the behavioral baseline which exists prior to drug administration. Discontinuation of drug treatment resulted in disruption of avoidance performance which was most pronounced in the ZM rats. In addition, drug termination produced disruption of discrimination performance, providing further evidence that the behavioral decrement was due to dissociation (stimulus change) between the drug and nondrug states.

Permanent facilitation of avoidance behavior by d-amphetamine and scopolamine.

Scopolamine (0.3, 0.6, 1.2, 2.4, 4.8 mg/kg) or d-amphetamine (0.25, 0.50, 1.00, 2.00, 4.00 mg/kg) was administered daily to independent groups of rats 30 min prior to training in a discriminated, Y-maze avoidance task. A dose-dependent relationship was found between amount of avoidance facilitation and drug dosage. Discontinuation of the drug following asymptotic performance resulted in a decrement in avoidance which varied as a function of the acquisition dosage. Results from a second experiment using the same task indicated that gradually reducing the dosage on consecutive training days rather than abruptly discontinuing the drug was more effective in producing permanent avoidance facilitation in the non-drug condition.

Self-Regulation of Brain-Stimulating Current Intensity in the Rat

A modification of the self-stimulation technique of Olds enabled rats to regulate and maintain at a preferred level the amount of brain-stimulating current they received as reinforcement for lever pressing. The method used two levers to deliver brief brain shocks: each response at one lever increased the current intensity a small step and each response at the other lowered it one step.

Chlorpromazine and amphetamine effects on three operant and on four discrete trial reinforcement schedules

Several doses of chlorpromazine (CPZ) and amphetamine (AMP) were given to rats trained on one of three operant schedules of reinforcement (VI 60″, FI 60″, or FR 100) or one of three discrete trial schedules (conditioned approach, CA; conditioned discrimination, CD; or stimulus self selection, SSS). The discrete trial procedures were more resistant to disruption by CPZ than were the operant schedules. AMP facilitated behavior only in the VI and FI schedules and had differential effects in the CD schedule (milk reward showed much greater resistance to disruption than water rewarded behavior). AMP was also given to Ss trained to respond on one of three response levers for milk, water or food reinforcement. Food responding was most disrupted while milk responding was least disrupted. It is concluded that depressants—like CPZ—can be studied equally well in many behavioral procedures while compounds which activate—like amphetamine—require a variety of behavioral procedures to show their many different effects.

THE EFFECTS OF TRANQUILIZERS ON POSITIVELY AND NEGATIVELY MOTIVATED BEHAVIOR IN RATS.

SummaryPrevious work using conditioned avoidance procedures to study the actions of tranquilizers frequently failed to determine whether the effect of these drugs in blocking the negatively motivated avoidance behavior was due to nonspecific effects on motor activity and/or stimulus input. The procedure used here differentiated these effects by combining conditioned approach and conditioned avoidance trials in a single experimental session, and by studying drug action when the animals were running under no shock, extinction conditions. The results showed clearly that appropriate doses of meprobamate, chlorpromazine and reserpine act primarily on the negatively motivated behavior and at these doses did not have a general effect on motor acticity or stimulus input.

Performance as a function of drug, dose, and level of training.

Chlorpromazine (CPZ) at 1.0, 2.0 and 3.0 mg/kg and LSD-25 at 0.05, 0.10, and 0.15 mg/kg were administered to Ss given varying amounts of training on a discrete trial conditioned approach procedure. Both CPZ and LSD-25 showed significant dose-response effects, i.e., as dose increased, degree of behavioral depression increased. There was no relationship between the LSD-25 induced depression and the amount of training but CPZ showed significantly less effect on highly trained behavior than on moderately or minimally trained behavior.

Time Factors in Interhemispheric Transfer of Learning

Single-trial interhemispheric transfer of a discrimination task engram was studied by eliciting spreading depression unilaterally during acquisition of the discrimination. Complete transfer to the untrained side occurred after one trial with both hemispheres functional, if 10 minutes elapsed between this trial and the elicitation of spreading depression in the trained side. If depression was elicited 15 seconds after the trial no transfer occurred. correct response highly probable.