Rohypnol ("roofies") control of drug discrimination: effect of coadministered ethanol or flumenazil.
The benzodiazepine flunitrazepam (Rohypnol) was employed to control differentially discriminative performance in 10 Sprague-Dawley rats on a food-motivated FR10 schedule. The training dose was 2.5 mg/kg, and 20 min was employed between intraperitoneal administration and training; both values were employed in this study, which, in reality, is the first time in the drug discrimination literature for the training of this drug. Dose-response experiments indicated decreasing discriminative performance in concert with decreasing time to reach FR10 lever selection as the dose tested decreased from 2.5 to 0.04 mg/kg. The calculated ED50 for discriminative performance, i.e., lever selection of the drug-correct lever, was 0.076 mg/kg. The relatively few sessions needed to reach discrimination criterion, and the fact that the ED50 value was 1/33 of the training dose, suggests that a lower dose of Rohypnol may be used in the future to train rats in this paradigm. Time course experiments indicate decreasing discriminative performance from 20-240 min postadministration with a calculated half-life of 162.3 min. Administration of 450, 600, and 900 mg/kg ethanol (10% w/v) I.P. produced saline-like discriminative responding, whereas the combination of these doses with the 0.08 mg/kg Rohypnol dose produced increasing discriminative performance with the highest ethanol dose producing 72.2% Rohypnol-appropriate lever selections in a mean time to attain lever selection on the FR10 schedule of 12.8 s. These results suggest that a lower training dose of Rohypnol may allow for testing of a smaller ED50 Rohypnol dose with ethanol to produce a more complete generalization. The ability of flumenazil (Ro 15-1788) to dose dependently block the discrimination of Rohypnol suggests that this benzodiazepine produces its action by its agonistic efficacy at these receptors. The coadministration of Rohypnol and ethanol as a popular drug combination in humans is discussed, and evidence is offered as to their synergistic interactions in rat discrimination.
Schechter
M D
MD
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272, USA.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000431:Ethanol / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology*; D005445:Flunitrazepam / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D014151:Anti-Anxiety Agents; D018756:GABA Antagonists; D000431:Ethanol; D005442:Flumazenil; D005445:Flunitrazepam