Abstract
5-Hydroxytryptamine (5-HT; serotonin) administration enhances GABAergic synaptic activity recorded in pyramidal neurons of the CA1 region of hippocampus. Previous studies have attributed this effect to the activation of HT-53 receptors located on GABAergic interneurons. During unrelated experiments, we noticed that under our recording conditions, 5-HT can still increase GABAergic synaptic activity after the complete blockade of 5-HT3 receptors. This indicated the involvement of an additional 5-HT receptor subtype. Therefore, we reinvestigated the effects of 5-HT on GABAergic synaptic activity recorded in pyramidal cells of the CA1 region. The ability of 5-HT to increase GABAergic synaptic activity in the presence of 5-HT3 receptor blockade was mimicked by the selective 5-HT2 agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and blocked by the selective 5-HT2 antagonist ketanserin. This indicated that the additional 5-HT receptor belongs to 5-HT2 receptor family. 5-HT2 receptor activation resulted in an increase in the frequency of spontaneous inhibitory postsynaptic currents as well as a shift in their amplitude distribution toward larger sizes. These effects were absent in the presence of tetrodotoxin. We interpret these results to indicate that 5-HT2 receptors activate GABAergic interneurons in the slice, leading to an increase in GABAergic synaptic activity onto pyramidal cells of the CA1 region.
Footnotes
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Send reprint requests to: Dr. Rodrigo Andrade, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2309 Scott Hall, 540 E. Canfield, Detroit, MI 48201. E-mail randrade{at}med.wayne.edu
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↵1 This work was supported by NIH grants MH43985 (R.A) and AA09829 (R.S.).
- Abbreviations:
- GABA
- γ-aminobutyric acid
- 5-HT
- 5-hydroxytryptamine
- mIPSC
- miniature inhibitory postsynaptic current
- K-S
- Kolmogorov-Smirnov
- sIPSC
- spontaneous inhibitory postsynaptic current
- TTX
- tetrodotoxin
- APV
- DL-2-aminophosphonovaleric acid
- CNQX
- 6-cyano-7-nitro-quinoxaline-2,3-dione
- 2-Me-5-HT
- 2-methyl-5-hydroxytryptamine maleate
- DOI
- (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
- Received March 31, 1997.
- Accepted January 15, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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