Functional tolerance to the hypothermic effect of phenobarbital in rats.

Phenobarbital elicits a hypothermic effect in rats. To determine if functional tolerance develops to this effect on temperature, rats were treated twice daily with IP injections of sodium phenobarbital (PheB) or saline. The PheB doses were increased over 21 days and then were held constant for another 23 days. On the next day (day 45) animals from both groups were given 80, 110 or 160 mg/kg PheB IP and the decrease in rectal temperature after 2 h was determined. Animals were decapitated after the temperature measurement and brain PheB levels were determined. A 1.51-fold shift in the relationship between brain level and response was found for the group given chronic PheB. These results show functional tolerance occurs to the hypothermic effect of PheB. This experiment was done in animals that were on a restricted food regimen. Rats given chronic PheB lost more weight than the group given chronic saline unless extra food was provided. We found that this occurred because the rats given chronic PheB lost more food through the wire cage floor than rats given chronic saline.

Similar development of tolerance to barbital-induced inhibition of avoidance behavior and loss of righting reflex in rats.

In order to determine if tolerance develops to the inhibition of avoidance behavior by the barbiturates, the effects of barbital on avoidance were determined in rats given barbital in their sole source of drinking water for 7 or 33 days. For comparison tolerance to the loss of righting reflex was also determined in other rats at the same time. All rats were trained by one 60-min session in a one-way active avoidance task; they were then put on the chronic drug administration schedule and then tested on the appropriate day after a single IP injection of 250 mg/kg sodium barbital. To assess the degree of tolerance, the brain level of barbital found at the biological endpoint--the loss of avoidance or loss of righting reflex--was compared in the chronic barbital treated rats and controls. A similar degree of tolerance developed to both effects of the drug and it appeared to be as great after 7 as after 33 days of chronic barbital treatment.

Effects of different delay of reinforcement procedures on variable-interval responding.

Two experiments studied responding in the rat when the first bar press after a variable period of time produced a cue light that remained on for either 10, 30, or 100 sec and terminated with the delivery of food. In Experiment I, response rate decreased and time to the first response after reinforcement increased as the delay of reinforcement increased. Similar results were obtained whether the delay consisted of retracting the lever during the delay, a fixed delay with no scheduled consequence for responding, or every response during the delay restarted the delay interval. In Experiment II, fixed-delay and fixed-interval schedules of the same duration during the delay period had no differential effect on either response rate or time to the first response after reinforcement, but differentially controlled responding during the delay periods.

Effects of conditioned reinforcement frequency in an intermittent free-feeding situation.

Key-pecking intermittently produced a set of brief exteroceptive stimulus changes under two-component multiple schedules of conditioned reinforcement. Throughout the study, free access to grain was concurrently provided on an intermittent basis via a variable-interval tape. Free food presentations scheduled by the tape were delivered if no peck had been emitted for 6 sec, and the brief stimulus changes produced by responding under the multiple schedules were those which accompanied food presentation. The second component of each multiple schedule was always associated with a 1-min, variable-interval schedule of conditioned reinforcement. The schedule associated with the first component was systematically varied and conditioned reinforcement was either absent (extinction) or programmed on a 1-, 3-, 6-, or 12-min variable-interval schedule. Under these conditions, rate of responding in the manipulated component decreased monotonically with a decrease in the frequency of conditioned reinforcement. In addition, contrast effects were often obtained in the constant, second component. These results are similar to those obtained with similar multiple schedules of primary reinforcement.