Discriminative stimulus effects of (-)-ephedrine in rats: Analysis with catecholamine transporter and receptor ligands

Lance R. McMahon, Kathryn A. Cunningham

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


A drug discrimination procedure was used to examine the neuropharmacology of (-)-ephedrine (5 mg/kg), a sympathomimetic amine found in a variety of dietary supplements. (-)-Ephedrine has caused concern because of its use as a precursor in the manufacture of street drugs (e.g. methamphetamine) and its potential for abuse and toxicity. In the present study, the catecholamine reuptake inhibitors mazindol and nomifensine, the norepinephrine (NE) reuptake inhibitor desipramine, and the dopamine D2-like (e.g. D2, D3 and D4) agonist quinpirole substituted for (-)-ephedrine (≥80% (-)-ephedrine-lever responding). The NE reuptake inhibitor nisoxetine, the D1-like (e.g. D1 and D5) agonists (±)-SKF 38393 and SKF 82958, and the mixed D1-/D2-like agonist apomorphine occasioned intermediate levels of responding (50-79% (-)-ephedrine-lever responding). The (-)-ephedrine cue was antagonized by the D1-like antagonist SCH 23390 and the α1-adrenoceptor antagonist prazosin as well as the D2-like antagonists (-)-eticlopride and haloperidol, although only at doses that disrupted responding in some rats. The discriminative stimulus effects of a small dose of (-)-ephedrine (1.25 mg/kg) were enhanced by the α2-adrenoceptor antagonist idazoxan and to a lesser extent by the β-adrenoceptor antagonist (-)-propranolol. However, the α2-adrenoceptor agonist clonidine (0.04 mg/kg) did not attenuate the (-)-ephedrine stimulus. These results suggest that D1-, D2-like, and α1-adrenergic receptors mediate the discriminative stimulus effects of (-)-ephedrine. Substitution of desipramine for (-)-ephedrine and not for some other stimulants suggests that NE transmission is a prominent feature of the (-)-ephedrine discriminative stimulus, and that NE underlies therapeutic and abuse-related effects of (-)-ephedrine that diverge from those of other stimulants.

Original languageEnglish (US)
Pages (from-to)255-264
Number of pages10
JournalDrug and Alcohol Dependence
Issue number3
StatePublished - Jun 5 2003
Externally publishedYes


  • Dopamine
  • Drug discrimination
  • Ephedrine
  • Ma Huang
  • Norepinephrine
  • Rat

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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