Serotonergic mediation of fenfluramine discriminative stimuli in fawn-hooded rats.
Fenfluramine, a drug that induces increased synaptic serotonin, was used to train Fawn-Hooded rats in a drug discrimination paradigm. This strain of rats is thought to possess a genetic serotonin storage abnormality. The intent of the study was to see if the Fawn-Hooded rat was similar or dissimilar to the more frequently used strain of Sprague-Dawley rat in its ability to learn to discriminate 2.0 mg/kg fenfluramine administered intraperitoneally. In addition, drugs presumed to work upon central serotonergic neurons were given to the fenfluramine-trained Fawn-Hooded rats to investigate if the cueing properties of the training drug generalized to other agents. Results indicate that the Fawn-Hooded rats learn to discriminate fenfluramine from its vehicle at the same rate, and with a similar sensitivity to lower doses, as do the Sprague-Dawley rats. Furthermore, fenfluramine was shown to completely generalize to MDMA (over 90%); TFMPP, m-CPP, quipazine and fluoxetine produced intermediate results (over 70%) and 5-MeODMT and ibogaine were vehicle-like (less than 70%). As these results coincide with those previously found in Sprague-Dawley rats, the conclusion is that the functional capacity to discriminate fenfluramine appears to be like that of other rat lines, and serotonergically-mediated, in the Fawn-Hooded rat. Suggestions to explain these results are offered and discussed.
Schechter
M D
MD
Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272, USA.
D000818:Animals; D004193:Discrimination Learning; D004305:Dose-Response Relationship, Drug; D005277:Fenfluramine / Q000008:administration & dosage / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology; D007050:Ibogaine / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D010879:Piperazines; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; C018406:1-(3-trifluoromethylphenyl)piperazine; D005277:Fenfluramine; D012701:Serotonin; D007050:Ibogaine; D011814:Quipazine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015068:1-(3-chlorophenyl)piperazine