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Enhancement of fluoxetine-dependent increase of extracellular serotonin (5-HT) levels by (−)-pindolol, an antagonist at 5-HT1A receptors

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Abstract

The somatodendritic 5-HT1A autoreceptor is known to regulate activity of 5-HT neurons and consequently 5-HT release. Administration of a selective 5-HT uptake inhibitor, fluoxetine (10 mg/kg, i.p.) increased extracellular 5-HT levels in rat hypothalamus up to 260 percent of basal levels. (−)-Pindolol, an antagonist at the somatodendritic 5-HT1A autoreceptor, dose-dependently (1, 3 and 5 mg/kg, s.c.) potentiated the fluoxetine dependent increase up to 458 percent of basal 5-HT levels for approximately 1.5 hours. Continuous infusion of (±)-pindolol at 30 mg/kg/h s.c. enhanced the fluoxetine dependent elevation of extracellular 5-HT concentrations in hypothalamus up to 464 percent of basal levels and lasted for 3 hours. Thus, the combination of 5-HT uptake inhibition with antagonism at the somatodendritic 5-HT1A autoreceptor can enhance 5-HT release to levels beyond those achieved with uptake inhibition alone. The present findings are consistent with the hypothesis that blockade of somatodendritic 5-HT1A autoreceptors removes the inhibitory effect exerted by the elevated 5-HT levels resulting from uptake inhibition.

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Authors and Affiliations

  1. Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, 46285, Indianapolis, IN

    Laura J. Dreshfield, David T. Wong, Kenneth W. Perry & Eric A. Engleman

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  1. Laura J. Dreshfield
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  2. David T. Wong
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  3. Kenneth W. Perry
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  4. Eric A. Engleman
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Dreshfield, L.J., Wong, D.T., Perry, K.W. et al. Enhancement of fluoxetine-dependent increase of extracellular serotonin (5-HT) levels by (−)-pindolol, an antagonist at 5-HT1A receptors. Neurochem Res 21, 557–562 (1996). https://doi.org/10.1007/BF02527753

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