Psychopharmacology

, Volume 65, Issue 2, pp 197–204 | Cite as

Effects of acute and chronic interactions of diazepam and d-Amphetamine on punished behavior of rats

  • Robert D. Ford
  • Richard H. Rech
  • Randall L. Commissaris
  • Linda Y. Meyer
Original Investigations

Abstract

Drinking of water-deprived rats was punished by delivery of either 0.03 or 0.1 mA shocks through the drinking tube during the last 5 of 7-s tone components during a 15-min daily exposure to water. These sessions consisted of 66 alternating components marked by the presence or absence of a tone. Drinking was not punished during the 33 components without tones or during the first 2 s of each tone. The baseline number of shocks accepted by the rats at 0.1 mA was less than half that at 0.03 mA. Acute diazepam markedly increased shocks delivered from the baseline values for both shock intensities, while acute d-amphetamine either had no effect or decreased the number of shocks accepted. The combination of acute diazepam and d-amphetamine caused a decrease in shock rates as compared to diazepam alone. Daily treatment with the combination of 10 mg/kg diazepam and 1 mg/kg d-amphetamine caused a gradual increase in punished responding over 25 days under either shock intensity. Gross observation of these rats after daily treatments indicated the development of hyperreactivity and a pattern resembling stereotyped behavior. At the end of the chronic treatment with the drug combination the shock rates were significantly greater than those caused by diazepam alone. Nevertheless, neither the effect of diazepam nor that of d-amphetamine, when administered singly after the period of chronic treatment with the combination, differed significantly from initial effect of the respective drugs on punished responding.

Key words

Diazepam d-Amphetamine Punished behavior Drug interaction 

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References

  1. Abdallah, A. H., White, H. D., Kulkarni, A. S.: Interaction of d-amphetamine with central nervous system depressants on food intake and spontaneous motor activity of mice. Eur. J. Pharmacol. 26, 119–121 (1974)Google Scholar
  2. Babbini, M., Montanaro, N., Strocchi, P., Gaiardi, M.: Enhancement of amphetamine-induced stereotyped behavior by benzodiazepines. Eur. J. Pharmacol. 13, 330–340 (1971)Google Scholar
  3. Barrett, J. E., Witkin, J. M.: Interaction of d-amphetamine with pentobarbital and chlordiazepoxide: Effects on punished and unpunished behavior of pigeons. Pharmacol. Biochem. Behav. 5, 285–292 (1976)Google Scholar
  4. Beer, B., Chasin, M., Clody, D. E., Vogel, J. R.: Cyclic adenosine monophosphate phosphodiesterase in brain: Effect of anxiety. Science 176, 428–430 (1972)Google Scholar
  5. Branch, M. N.: Behavior as a stimulus: Joint effects of d-amphetamine and pentobarbital. J. Pharmacol. Exp. Ther. 189, 33–41 (1974)Google Scholar
  6. Byck, R.: Drugs and the treatment of psychiatric disorders. In: The pharmacological basis of therapeutics, L. S. Goodman, A. Gilman, eds., pp. 152–200. New York: MacMillan 1975Google Scholar
  7. Consolo, S., Garattini, S., Ladinsky, H.: Action of the benzodiazepines on the cholinergic system. In: Mechanism of action of benzodiazepines, E. Costa, P. Greengard, eds., pp. 63–80. New York: Raven 1975Google Scholar
  8. Cook, L., Sepinwall, J.: Behavioral analysis of the effects and mechanism of action of benzodiazepines. In: Mechanism of action of benzodiazepines, E. Costa, P. Greengard, eds., pp. 1–44. New York: Raven 1975Google Scholar
  9. Cox, C., Harrison, P. E., Steinberg, H., Tomkiewicz, M.: Lithium attenuates drug-induced hyperactivity in rats. Nature 232, 336–337 (1971)Google Scholar
  10. Ellinwood, E. H., Eibergen, R. D., Kilbey, M. M.: Stimulants: Interaction with clinically relevant drugs. Ann. N. Y. Acad. Sci. 281, 393–408 (1976)Google Scholar
  11. Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia 10, 316–323 (1967)Google Scholar
  12. Fuxe, K., Agnati, L. F., Bolme, P., Hokfelt, T., Lidbrink, P., Ljungdahl, A., de la Mora, M. P., Ogren, S.: The possible involvement of GABA mechanisms in the action of benzodiazepines on central catecholamine neurons. In: Mechanism of action of benzodiazepines, E. Costa, P. Greengard, eds., pp. 45–61. New York: Raven 1975Google Scholar
  13. Garattini, S., Mussini, E., Marcucci, F., Guaitani, A.: Metabolic studies on benzodiazepines in various animal species. In: The benzodiazepines, S. Garattini, E. Mussini, L. O. Randall, eds., pp. 75–97. New York: Raven 1973Google Scholar
  14. Geller, I.: Relative potencies of benzodiazepines as measured by their effects on conflict behavior. Arch. Int. Pharmacodyn. Ther. 149, 243–247 (1964)Google Scholar
  15. Geller, I., Seifter, J.: The effect of meprobamate, barbiturates, d-amphetamine and promazine on experimentally-induced conflict in the rat. Psychopharmacologia 1, 482–491 (1960)Google Scholar
  16. Haefely, W. E.: Behavioral and neuropharmacological aspects of drugs used in anxiety and related states. In: Psychopharmacology: A generation of progress, M. A. Lipton, A. Di Mascio, K. F. Killam, eds., pp. 1359–1374. New York: Raven 1978Google Scholar
  17. Longoni, A., Mandelli, V., Pessotti, I.: Study of antianxiety effects of drugs in the rat, with a multiple punishment and reward schedule. In: The benzodiazepines, S. Garattini, E. Mussini, L. O. Randall, eds., pp. 347–354. New York: Raven 1973Google Scholar
  18. Magos, L.: Persistence of the effect of amphetamine on stereotyped activity in rats. Eur. J. Pharmacol. 6, 200–201 (1969)Google Scholar
  19. McMillan, D. E.: Drugs and punishment. Rate-dependent effects under multiple schedules. J. Exp. Anal. Behav. 1, 133–145 (1973a)Google Scholar
  20. McMillan, D. E.: Punishment intensity as a determinant of drug effect. Psychopharmacologia (Berl.) 30, 61–74 (1973b)Google Scholar
  21. Miczek, K. A.: Effects of scopolamine, amphetamine and chlordiazepoxide on punishment. Psychopharmacologia 28, 373–389 (1973)Google Scholar
  22. Portou, P., Boulu, R., Bohuon, C.: Effect of lithium and other drugs on the amphetamine-chlordiazepoxide hyperactivity in mice. Experientia 31, 99–101 (1975)Google Scholar
  23. Randall, L. O., Kappell, B.: Pharmacological activity of some benzodiazepines and their metabolites. In: The benzodiazepines, S. Garattini, E. Mussini, L. O. Randall, eds., pp. 27–51. New York: Raven 1973Google Scholar
  24. Rech, R. H., Stolk, J. M.: Amphetamine-drug interactions that relate brain catecholamines to behavior. In: Amphetamines and related compounds, E. Costa, S. Garattini, eds., pp. 385–413. New York: Raven 1970Google Scholar
  25. Richelle, M.: Combined action of diazepam and d-amphetamine on fixed-interval performance in cats. J. Exp. Anal. Behav. 12, 989–998 (1969)Google Scholar
  26. Rushton, R., Steinberg, H.: Dose-response relations of amphetamine-barbiturate mixtures. Nature 197, 1017–1018 (1963a)Google Scholar
  27. Rushton, R., Steinberg, H.: Mutual potentiation of amphetamine and amylobarbitone measured by activity in rats. Br. J. Pharmacol. 21, 295–305 (1963b)Google Scholar
  28. Rutledge, C. O., Kelleher, R. T.: Interactions between the effects of methamphetamine and pentobarbital on operant behavior in the pigeon. Psychopharmacologia 7, 400–408 (1965)Google Scholar
  29. Stein, L., Wise, C. D., Belluzzi, J. D.: Effects of benzodiazepines on central serotonergic mechanisms. In: Mechanism of action of benzodiazepines, E. Costa, P. Greengard, eds., pp. 29–44. New York: Raven 1975Google Scholar
  30. Taylor, K. M., Laverty, R.: The effect of chlordiazepoxide, diazepam and nitrazepam on catecholamine metabolism in regions of the rat brain. Eur. J. Pharmacol. 8, 296–301 (1969)Google Scholar
  31. Vogel, J. R., Beer, B., Clody, D. E.: A simple and reliable conflict procedure for testing antianxiety agents. Psychopharmacologia 21, 1–7 (1971)Google Scholar
  32. Wilson, M. C.: The effect of cocaine and d-amphetamine on punished responding. Arch. Int. Pharmacodyn. Ther. 227, 98–105 (1977)Google Scholar
  33. Woodruff, M. L.: Attenuation of the rate-dereasing effects of amphetamine on fixed-ratio responding in rats by hippocampal lesions. Behav. Biol. 20, 493–499 (1977)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Robert D. Ford
    • 1
  • Richard H. Rech
    • 1
  • Randall L. Commissaris
    • 1
  • Linda Y. Meyer
    • 1
  1. 1.Department of Pharmacology and ToxicologyMichigan State UniversityEast LansingUSA

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