Date of Award
Doctor of Philosophy in Psychology
Nelson F. Smith
Intraperitoneal injection of phenyl-p-benzoquinone (PBQ) was used in three experiments to evaluate its action as a potential model for the study of "pain" processes. Pain is operationally defined as: behavior which would be interpreted as pain related in man, specific actions of analgesic drugs to reduce this behavior, and ability of other pain producing chemicals to substitute for the PBQ treatment. In the first experiment PBQ administration produced dose-dependent writhing in hooded rats. This behavior was blocked by the narcotic analgesic, morphine, also in a dose dependent manner. In the second experiment 20 subjects were trained to respond on a fixed ratio 10 schedule for available for reinforcement. Two manipulanda were available for responding. One of the levers produced reinforcement only following an injection of PBQ, and responses on the other were only reinforced following a saline injection. Observation of performance over many trials indicated that PBQ was acting as a discriminative stimulus by significantly influencing lever choice prior to the delivery of reinforcement. However, the task was acquired with difficulty, was maintained at a low level of accuracy, and PBQ treatment was extremely toxic when given chronically. Procedural changes were incorporated in the third experiment to reduce or eliminate these problems. The dose of PBQ was levered from 1.25 mg/kg to 0.62 mg/kg, and the saline injection was omitted on non-PBQ trials. It was replaced by a handling treatment without injection. Twenty-six of a total of 49 subjects acquired the task, and a level of accuracy vas maintained which permitted the application of experimental treatments. The subjects all met a criterion level of performance of 9 or fewer responses on the incorrect lever prior to the first 10 responses on the correct lever for 8 out of 10 consecutive trial days.
Discrimination of the PBQ injection was dose related, with an ED 50 of 0.21 mg/kg representing the average threshold. Neither decreased toxicity nor increased ease of acquisition resulted from the procedural changes. An injection of saline administered in place of PBQ elicited PBQ -appropriate lever selection in 40% of the subjects; indicating that the discriminative stimulus vas a compound, with PBQ irritation the primary component and probable irritation from the injection procedure a secondary component. Injection of histamine produced PBQ lever selection in a significant majority of the subjects tested. These data suggest that the discriminative property of PBQ treatment is its irritant quality since this action is common to both PBQ and histamine.
To further study the validity of PBQ discrimination as a model of subjectively experienced aversive stimuli for investigation of pain related behavior, two analgesics and several other centrally acting drugs were administered with PBQ treatment on certain test trials. Both the narcotic analgesic morphine, and non-narcotic analgesic aspirin produced significant blockade of PBQ discrimination at doses which did not significantly affect response rate, linear function and the blocking action was a significant of ascending dose for morphine but not aspirin. Librium and haloperidol did not significantly affect PBQ depressed discrimination at doses responding. Pentobarbital which and severely amitriptyline interfered significantly with PBQ discrimination at one of several doses tested, but in a manner which excluded the effect as evidence of analgesic action. There was no significant dose-related blockade of discrimination by either drug, and the level of interference did not approach the effect of the two analgesic compounds tested.
It was concluded that PBQ treatment discrimination is based on both senscry and aversive components which are necessary to validate the task as a model of subjective pain processes. However, the problems of toxicity and performance reliability must be overcome before it can be used as a practical screening procedure for evaluating analgesic drug effects.
Miksic, Stephen, "Evaluation of Pain as a Discriminative Stimulus in the Rat" (1978). Open Access Dissertations. Paper 976.