Serotonergic mediation of fenfluramine discriminative stimuli in Fawn-Hooded rats

Abstract

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.

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