Lasting increase in serotonin 5-HT1A but not 5-HT4 receptor subtypes in the kindled rat dentate gyrus: dissociation from local presynaptic effects.

Abstract

We examined the effect of kindling on serotonergic neurotransmission in the hippocampus by measuring serotonin (5-HT) release and uptake in hippocampal synaptosomes and 5-HT1A and 5-HT4 receptor subtypes during and at different times after electrical kindling of the dentate gyrus. Using quantitative receptor autoradiography, we found that binding of 8-[3H]hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) to 5-HT1A receptors was selectively increased by 20% on average (p < 0.05) in the dentate gyrus of the stimulated and contralateral hippocampus 2 days after stage 2 (stereotypes and occasional retraction of a forelimb) and by 100% on average (p < 0.05) 1 week after stage 5 (tonic-clonic seizures) compared with sham-stimulated rats. A 20% increase (p < 0.05) was observed 1 month after the last generalized seizure. No changes were found after a single afterdischarge. 5-HT4 receptors, which colocalize with 5-HT1A receptors on hippocampal neurons, were not modified in kindled tissue. [3H]5-HT uptake and its release as well as the 5-HT1B autoreceptor function did not differ from shams in hippocampal synaptosomes at stages 2 and 5. Systemic administration of 100 and 1,000 microg kg(-1) 8-OH-DPAT or 1,000 microg kg(-1) WAY-100,635, 30 min before each electrical stimulation, did not significantly alter kindling progression or the occurrence of stage 5 seizures in fully kindled rats. The changes in 5-HT1A receptor density in the dentate gyrus are part of the plastic modifications occurring during kindling and may contribute to modulating tissue hyperexcitability.

• Authors: A Cagnotto, D Crespi, L Mancini, C Manzoni, M L Presti, M Gariboldi, A Vezzani, T Mennini
• Journal: Journal of neurochemistry (J Neurochem) Vol. 70 Issue 2 Pg. 850-7 (Feb 1998) ISSN: 0022-3042 [Print] England
• PMID: 9453582 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dioxanes
• Iodine Radioisotopes
• Piperazines
• Piperidines
• Pyridines
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT1
• SB 207710
• Serotonin Antagonists
• Tritium
• Receptors, Serotonin, 5-HT4
• Serotonin
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
• 8-Hydroxy-2-(di-n-propylamino)tetralin

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (metabolism, pharmacology)
• Animals
• Cerebral Cortex (drug effects, physiology)
• Dentate Gyrus (drug effects, physiology)
• Dioxanes (metabolism)
• Electric Stimulation
• Functional Laterality
• Hippocampus (physiology)
• Iodine Radioisotopes
• Kindling, Neurologic (physiology)
• Male
• Neurons (drug effects, physiology)
• Piperazines (pharmacology)
• Piperidines (metabolism)
• Pyridines (pharmacology)
• Radioligand Assay
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin (biosynthesis)
• Receptors, Serotonin, 5-HT1
• Receptors, Serotonin, 5-HT4
• Serotonin (metabolism)
• Serotonin Antagonists (metabolism, pharmacology)
• Synapses (physiology)
• Tritium