Discriminative stimulus properties of the serotonin uptake inhibitor sertraline.

Abstract

Rats (Rattus norvegicus) were trained to discriminate the stimulus properties of the antidepressant serotonin (5-hydroxytryptamine; 5-HT) uptake inhibitor sertraline (10 mg/kg) from saline using the discriminated taste aversion procedure. Three other selective 5-HT uptake inhibitors, fluvoxamine (5.6 and 10.0 mg/kg), fluoxetine (10.0 mg/kg), and paroxetine (10.0 mg/kg), substituted completely for the stimulus properties of sertraline. Selective inhibitors of norepinephrine uptake, desipramine and maprotiline, also substituted for the sertraline stimulus at 18.0 mg/kg. The results of the present study show that rats can be trained to respond to sertraline as a discriminative stimulus and that sertraline generalizes to other 5-HT uptake inhibitors that are members of a class of antidepressant drugs.Clinically effective antidepressant drugs represent a pharmacologically diverse group of compounds. Antidepressant drugs include monoamine oxidase inhibitors, selective and nonselective inhibitors of norepinephrine (NE) and serotonin (5hydroxytryptamine; 5-HT) uptake, and atypical compounds (for review, see Frazer & Brunswick, 1990;Heninger & Charney, 1987). The physiological mechanisms mediating the clinical efficacy of these compounds are unknown. The technique of drug discrimination provides a method by which the effects of antidepressant drugs can be measured in a behaviorally functional context and might provide information concerning the neural substrates associated with the behavioral effects of these compounds. Drug-discrimination procedures involve training an animal to respond differentially on administration of two selected compounds that produce different internal states, usually a drug and saline.

The role of serotonin receptor subtypes in treating depression: a review of animal studies

“…The SSRI citalopram has been trained as a discriminative stimulus and other SSRIs, sertraline and paroxetine, but not diazepam or clozapine fully substituted for citalopram (Millan et al 1999). Other groups have also shown successful training of SSRIs as discriminative stimuli (Kreiss and Lucki 1994; Marona-Lewicka and Nichols 1998; Wolff and Leander 1999) and their stimulus effects did not generalize to selective norepinephrine reuptake inhibitors. Although discriminative stimulus properties of ADs can be used to identify and study compounds with neuropharmacological similarities, the basis for their similarity cannot be shown to be related to their AD properties (Dekeyne and Millan 2003).…”

Stimulus properties of fluvoxamine in a conditioned taste aversion procedure

“…To our knowledge, there is only one report of a drug discrimination of an SSRI that has been successful : in a discriminated taste aversion, Kreiss and Lucki (1994) trained rats to discriminate sertraline from saline. Sertraline generalized to ßuoxetine, to ßuvoxamine, and to the 5-HT 1B / 2C receptor agonist TFMPP [N-(3-trißuoromethylphenyl)piperazine], but only partially to the 5-HT 1A receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT).…”