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Effects of chronic d-amphetamine treatment on schedule-controlled behavior

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Abstract

The effect of d-amphetamine added to the drinking water on the rate of conditioned lever pressing by rats was determined using fixed-ratio 30 (FR-30) and fixed-interval 2-min (FI-2) schedules of food presentation. After 32 days of gradual increase in drug concentration the average drug ingestion was 13 mg/kg/day. In tests with various doses of d-amphetamine injected before and after the chronic ingestion regimen, the rate-decreasing effects of d-amphetamine on FR responding were attenuated after chronic treatment, indicating development of a two- to three-fold tolerance. However, the rate-decreasing effect of d-amphetamine on FI responding was not altered by chronic ingestion. Since acute amphetamine treatment reduced the reinforcement frequency under the FR but not the FI schedule, these results are consistent with the hypothesis that a ‘behavioral tolerance’ will develop most readily to drug effects that decrease the frequency of reinforcement. Upon removal of d-amphetamine from the drinking water there was some increase in the rate of FR responding, but no change in FI responding.

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References

  • Ferster, C. V., Skinner, B. F.: Schedules of reinforcement. New York: Appleton-Century-Crofts 1957

    Google Scholar 

  • Fischman, M. W., Schuster, C. R.: Tolerance development to chronic methamphetamine intoxication in the rhesus monkey. Pharmacol. Biochem. Behav. 2, 503–508 (1974)

    Google Scholar 

  • Gotestam, K. G., Lewander, T.: The duration of tolerance to the anorexigenic effect of amphetamine in rats. Psychopharmacologia 42, 41–45 (1975)

    Google Scholar 

  • Harris, R. A., Snell, D.: Phenobarbital and d-amphetamine tolerance development: Behavioral factors. Fed. Proc. 37. Abs. 2350 (1978)

  • Harrison, J. W. E., Ambrus, C. M., Ambrus, J. L.: Tolerance of rats toward amphetamine and methamphetamine. J. Am. Pharm. Assoc. 41, 539–541 (1952)

    Google Scholar 

  • Hitzemann, R. J., Loh, H. H., Craves, F. B., Domino, E. F.: The use of d-amphetamine pellet implantation as a model for d-amphetamine tolerance in the mouse. Psychopharmacologia 30, 227–240 (1973)

    Google Scholar 

  • Kalant, H., LeBlanc, A. E., Gibbins, R. J.: Tolerance to and dependence on, some non-opiate psychotropic drugs. Pharmacol. Rev. 23, 135–191 (1971)

    Google Scholar 

  • Kosman, M. E., Unna, K. R.: Effects of chronic administration of the amphetamines and other stimulants on behavior. Clin. Pharmacol. Ther. 9, 240–254 (1968)

    Google Scholar 

  • Leander, J. D., McMillan, D. E.: Rate dependent effects of drugs. I. Comparisons of d-amphetamine, pentobarbital, and chlorpromazine on multiple and mixed schedules. J. Pharmacol. Exp. Ther. 188, 726–739 (1974)

    Google Scholar 

  • Lewander, T.: A mechanism for the development of tolerance to amphetamine in rats. Psychopharmacologia 21, 17–31 (1971)

    Google Scholar 

  • Magour, S., Coper, H., Fahndrich, C.: The effects of chronic treatment with d-amphetamine on food intake, body weight, locomotor activity and subcellular distribution of the drug in rat brain. Psychopharmacologia 34, 45–54 (1974)

    Google Scholar 

  • Magour, S., Coper, H., Fahndrich, C.: The effect of chronic selfadministration of d-amphetamine on food intake, locomotor activity and C14-leucine incorporation into cerebral cortex protein. Psychopharmacologia 45, 267–270 (1976)

    Google Scholar 

  • McMillan, D. E.: Effects of d-amphetamine on performance under several parameters of multiple fixed-ratio, fixed-interval schedules. J. Pharmacol. Exp. Ther. 167, 26–33 (1969)

    Google Scholar 

  • Mercier, J., Dessaigne, S.: Determination de l'accoutumance experimentale par une methode psychophysiologique (III. Memoire). Etudes de quelques medicaments psychotoniques. Ann. Pharm. Fr. 17, 606–615 (1959)

    Google Scholar 

  • Minkowsky, W. L.: The effects of benzedrine sulphate upon learning. J. Comp. Psychol. 28, 349–360 (1939)

    Google Scholar 

  • Schuster, C. R., Dockens, W. S., Woods, J. H.: Behavioral variables affecting the development of amphetamine tolerance. Psychopharmacologia 9, 170–182 (1966)

    Google Scholar 

  • Schuster, C. R., Fischman, M. W.: Amphetamine toxicity: Behavioral and neuropathological indexes. Fed. Proc. 34, 1845–1851 (1975)

    Google Scholar 

  • Schuster, C. R., Zimmerman, J.: Timing behavior during prolonged treatment with dl-amphetamine. J. Exp. Anal. Behav. 4, 327–330 (1961)

    Google Scholar 

  • Stolerman, I. P., Kumar, R., Steinberg, H.: Development of morphine dependence in rats: lack of effect of previous ingestion of other drugs. Psychopharmacologia 20, 321–336 (1971)

    Google Scholar 

  • Thompson, D. M.: Repeated acquisition of behavioral chains under chronic drug conditions. J. Pharmacol. Exp. Ther 188, 700–713 (1974)

    Google Scholar 

  • Tilson, H. A., Sparber, S. B.: Similarities and differences between mescaline, lysergic acid diethylamide-25 (LSD) and d-amphetamine on various components of fixed-interval responding in the rats. J. Pharmacol. Exp. Ther. 184, 376–384 (1973a)

    Google Scholar 

  • Tilson, H. A., Sparber, S. B.: The effects of d-and l-amphetamine on fixed-interval and fixed-ratio behavior in tolerant and non-tolerant rats. J. Pharmacol. Exp. Ther. 187, 372–379 (1973b)

    Google Scholar 

  • Tormey, J., Lasagna, L.: Relation of thyroid function to acute and chronic effects of amphetamine in the rat. J. Pharmacol. Exp. Ther. 128, 201–209 (1960)

    Google Scholar 

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Harris, R.A., Snell, D. & Loh, H.H. Effects of chronic d-amphetamine treatment on schedule-controlled behavior. Psychopharmacology 63, 55–61 (1979). https://doi.org/10.1007/BF00426922

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