Original Investigations

Psychopharmacology

, Volume 74, Issue 1, pp 23-28

First online:

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

  • Nancy J. LeithAffiliated withDepartment of Pharmacology, Vanderbilt University Medical SchoolPsychology Research Laboratories, Veterans Administration Hospital Nashville
  • , Robert J. BarrettAffiliated withDepartment of Pharmacology, Vanderbilt University Medical SchoolPsychology Research Laboratories, Veterans Administration Hospital Nashville

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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