The main objective of this investigation was to evaluate the effects of buspirone,
a 5-HT(1A) agonist with some partial agonist properties and also an antidepressant,
on regional 5-HT synthesis in Flinders Sensitive Line (FSL) rats ("depressed"), and
to compare the effects to the Flinders Resistant Line (FRL) control rats (not "depressed").
In addition results were compared to those previously reported in normal Sprague-Dawley
(SPD) rats (normal control). Serotonin synthesis in both FSL and FRL rats was measured
following acute and chronic treatments with buspirone. Both of these strains were
derived from the SPD rats. No direct comparison was done between the FSL saline and
FRL saline groups, or the FSL buspirone and FRL buspirone groups, because the objective
of the studies was to evaluate effects of buspirone in these two strains. The results
show that acute treatment with buspirone elevates 5-HT synthesis throughout the brain
in the FRL rats. In the FSL rats, there were reductions in some brain regions (e.g.,
dorsal and median raphe, amygdala, anterior olfactory nucleus, substantia nigra reticulate),
while in other regions, there were increases in the synthesis observed (e.g., frontal,
parietal, visual and somatosensory cortices, ventral hippocampus). In 20 out of the
30 brain regions investigated in the FSL rats, there was no significant change in
the synthesis following acute buspirone treatment. During the chronic treatment, buspirone
produced a significant reduction of 5-HT synthesis in 15 out of 30 brain regions in
the FRL rats. In the FSL rats, buspirone produced a significant elevation of the synthesis
in 10 out of 30 brain regions. In both the FSL and FRL rats, buspirone produced rather
different effects than those reported previously for SPD (normal) rats. The acute
effect in the FSL rats was somewhat similar to the effect reported previously for
the SPD rats, while in the FRL rats, the acute buspirone treatment produced an effect
observed previously in treatments with 5-HT(1A) antagonists suggesting an action of
buspirone as partial agonist in FRL rats. The data suggest that with respect to 5-HT
synthesis, FRL rats differ from SPD rats (a natural control; normal rats) and, as
such, indicate that when the effects related to the serotonergic system (e.g., influence
of serotonergic drugs) are studied in the FSL rats and compared to those in the FRL
rats, any conclusions drawn may not reflect differences relative to a normal rat.