Date of Award
Master of Science in Pharmacology and Toxicology
Pharmacology and Toxicology
Behavior is under the control of external and internal stimuli. The emission of behavior is therefore most efficient when the stimulus-conditions similar to those under which the behavior was acquired are reinstated. Amphetamine was shown to produce a "stimulus-state" which controlled behavior. A decrement in response strength occurred when a response acquired under the influence of amphetamine was emitted in the absence of amphetamine or in the presence of no-drug. The response strength recovered when the amphetamine-state was reinstated. Rats were trained to jump to a wooden platform from an electrifiable grid-floor, in order to avoid shock. A buzzer was used as the conditioned stimulus. Seven days were allowed to elapse between testing and training. A conditioned avoidance response acquired under the influence of amphetamine was emitted without decrement under 1) 2.0 mg amphetamine per kg body weight, 2) 100 or 400 mg dl-3,4-dihydroxyphenylalanine per kg body weight, 3) 50 mg dl-a-methyl-p-tyrosine per kg body weight, 100 or 400 mg dl-3,4-dihydroxyphenylalaninc per kg body weight and 2.0 mg amphetamine per kg body weight, 4) 316 mg parachlorophenylalanineper kg body weight, 75 mg dl-5- hydroxytryptophan per kg body weight and 2. 0 mg amphetamine per kg body weight. However, the percent avoidance deteriorated markedly (all comparisons were statistically significant), when subjects trained under amphetamine were tested after pretreatment under 1) no injections, 2) dl-a-methyl-p-tyrosine and amphetamine, 3) parachlorophenylalanine and amphetamine, 4) hydroxyamphetamine (10 mg/kg or 30 mg/kg), 5) chlorpromazine (1 or 4 mg/kg) and amphetamine, 6) cyproheptadine (10 mg/kg) and amphetamine. Moreover, animals treated chronicc1lly with amphetamine, when trained under amphetamine, showed a decrement in response strength when tested under no-drug. A conditioned-avoidance response acquired under the influence of hydroxyamphetarnine (30 mg/kg) was emitted without decrement in response strength under either hydroxyamphetamine or no-drug. Further, a conditioned avoidance response acquired under the influence of d1-methyl-p-tyrosine and amphetamine was emitted without decrement in response strength under either c1-methyl-p-tyrosine and amphetamine or just amphetamine. These studies suggest that there exists a stimulus-state associated with amphetamine and that this behnvior-controlling state is not the result of the stimulant property of the drug. The drug-interaction studies suggest that central catocholamines and 5-hydroxytryptamine are involved in the amphetamine-state. Further, by varying the concentration of either amine, the amphetamine-state may be altered.
Roffman, Mark, "Learning Associated with the Amphetamine-State: Role of Brain Amines" (1970). Open Access Master's Theses. Paper 220.