B. Simon et Jb. Appel, DOPAMINERGIC AND SEROTONERGIC PROPERTIES OF FLUOXETINE, Progress in neuro-psychopharmacology & biological psychiatry, 21(1), 1997, pp. 169-181
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.