Psychopharmacology

, Volume 74, Issue 1, pp 23–28

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

Authors

  • Nancy J. Leith
    • Department of PharmacologyVanderbilt University Medical School
    • Psychology Research LaboratoriesVeterans Administration Hospital Nashville
  • Robert J. Barrett
    • Department of PharmacologyVanderbilt University Medical School
    • Psychology Research LaboratoriesVeterans Administration Hospital Nashville
Original Investigations

DOI: 10.1007/BF00431751

Cite this article as:
Leith, N.J. & Barrett, R.J. Psychopharmacology (1981) 74: 23. doi:10.1007/BF00431751

Abstract

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.

Key words

Self-stimulation d-Amphetamine l-Amphetamine Methylphenidate Cocaine Tolerance Post-drug depression p-Hydroxynorephedrine

Copyright information

© Springer-Verlag 1981