| DIFFERENT EFFECTS OF ACUTE AND CHRONIC TREATMENT WITH TIANEPTINE IN THE ACQUISITION OF CONDITIONED FEAR. | ||
| N.S.Burghardt1*; E.P.Bauer1; B.S.McEwen2; J.E.LeDoux1 | ||
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| SSRIs are effective in treating anxiety disorders, but
it is unclear why long-term treatment is required to achieve therapeutic
improvement. Previously, we evaluated the effects of acute and chronic
treatment with the SSRI citalopram on auditory fear conditioning and
found differences consistent with clinical findings. Conditioned fear
increased following acute administration and decreased after chronic
treatment. To further explore how alterations in 5-HT levels mediate
an anxiolytic effect, we evaluated the effects of acute vs. chronic
treatment with the putative serotonin reuptake enhancer, tianeptine,
on the acquisition and expression of auditory fear conditioning in
rats. Fear conditioning involved 2 presentations of a tone (20s, 10kHz)
that co-terminated with a footshock (0.7mA, 0.5s). One systemic injection
of tianeptine (10mg/kg) given 1hr before training or testing did not
affect conditioned freezing to the tone 24hr after training. In contrast,
chronic injections (21d) of tianeptine (10mg/kg) given before training
reduced conditioned freezing. Yet chronic injections (21d) of tianeptine
given after training did not reduce freezing. These results indicate
that an SSRI and a putative serotonin reuptake enhancer have different
effects on fear conditioning when administered acutely, but have the
same effect on the acquisition of conditioned fear when administered
chronically. Therefore, a common mechanism dowstream from the serotonergic
system may be altered by both drugs to mediate their chronic effect.
As a means of uncovering this mechanism we are investigating the role
of 5-HT3 receptors in the amygdala. Using in vitro recordings of lateral
amygdala excitatory cells, we found that the 5-HT3 antagonist tropisetron
(1uM) increased the size of IPSPs elicited by thalamic or cortical
input stimulation. We will evaluate how this increase in inhibition
might interact with antidepressant treatment. Support Contributed By: NIH grants MH58911, NS43899 |
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| Citation: N.S. Burghardt, E.P. Bauer, B.S. McEwen, J.E. LeDoux. DIFFERENT EFFECTS OF ACUTE AND CHRONIC TREATMENT WITH TIANEPTINE IN THE ACQUISITION OF CONDITIONED FEAR. Program No. 623.4. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Online. |
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