MDMA-like stimulus effects of hallucinogens in male Fawn-Hooded rats

Pharmacol Biochem Behav. 1998 Feb;59(2):265-70. doi: 10.1016/s0091-3057(97)00415-2.

Abstract

A two-lever, food-motivated, operant technique was employed to train the purportedly serotonergically dysfunctional Fawn-Hooded (FH) rat to discriminate 1.5 mg/kg MDMA. Once all 10 male subjects learned the MDMA-vehicle discrimination at criterion performance level, doses different than the training dose were used to generate a dose-response discrimination gradient. The ED50 value of MDMA was shown to be 0.136 mg/kg, not significantly different from that of previously trained Sprague-Dawley male rats. Thus, the Fawn-Hooded rat appears to not differ in its sensitivity to lower doses of MDMA. Testing for MDMA-like stimulus generalizations with other drugs indicated that the MDMA derivative MDE produced generalization at a dose of 2.25 mg/kg and allowed for an ED50 value of 0.496 mg/kg. Like MDE, the testing of alpha-ethyltryptamine was shown to produce MDMA-like responding. Lastly, a dose of 0.12 mg/kg LSD produced 90% MDMA-lever selection. In contrast to MDMA generalizations to these three drugs, testing of cocaine at doses of 2.5-10 mg/kg and mescaline at 8-14 mg/kg did not produce MDMA-like discriminative effects. The results of this testing in the presumably serotonergically dysfunctional Fawn-Hooded rat would indicate that this line not only can discriminate MDMA as well as heterogenous-bred lines, but also shows the same discriminative generalizations and nongeneralizations from MDMA to serotonergic and dopaminergic agents.

MeSH terms

  • Animals
  • Central Nervous System Stimulants / pharmacology*
  • Conditioning, Operant / drug effects
  • Cues
  • Discrimination, Psychological / drug effects
  • Dopamine Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Generalization, Stimulus / drug effects
  • Hallucinogens / pharmacology*
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Rats, Sprague-Dawley
  • Serotonin / genetics
  • Serotonin / physiology
  • Serotonin Agents / pharmacology

Substances

  • Central Nervous System Stimulants
  • Dopamine Agents
  • Hallucinogens
  • Serotonin Agents
  • Serotonin
  • N-Methyl-3,4-methylenedioxyamphetamine