DOPAMINERGIC AND SEROTONERGIC PROPERTIES OF FLUOXETINE

1. Rats were trained to discriminate i.p. injections of a 5-HT agonist , LSD (0.08 mg/kg, n = 12) or a DA agonist, cocaine (10 mg/kg; n = 16) in a two lever, drug discrimination situation. 2. Animals were tested with fluoxetine (0.625-10 mg/kg) alone and in combination with low do ses of the training drugs. 3. Fluoxetine did not substitute for either LSD or cocaine at any dose tested. A relatively low dose of fluoxetin e (2.5 mg/kg) potentiated the discriminability of cocaine (2.5 mg/kg) from saline. A higher dose of fluoxetine (5.0 mg/kg) significantly enh anced the effects of a low dose of LSD (0.02 mg/kg), but only to 41.7% responses on the LSD-appropriate lever. 4. The data suggest that fluo xetine alters the discriminative stimulus properties of cocaine to a g reater extent than those of LSD. 5. The ability of fluoxetine to poten tiate the cocaine cue (but not to substitute for cocaine) suggests tha t both of these drugs affect DA systems, but do so through different m echanisms. For example, fluoxetine may not inhibit DA reuptake (to the same extent as cocaine), but may have other dopaminergic actions such as increasing DA receptor density.