Lasting Increase in Serotonin 5‐HT1A but Not 5‐HT4 Receptor Subtypes in the Kindled Rat Dentate Gyrus: Dissociation from Local Presynaptic Effects

• Published in: Journal of neurochemistry Vol. 70; no. 2; pp. 850 - 857
• Main Authors: Cagnotto, A., Crespi, D., Mancini, L., Manzoni, C., Presti, M. L., Gariboldi, M., Vezzani, A., Mennini, T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.1998; Blackwell
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - metabolism; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; 8‐Hydroxy‐2‐(di‐n‐propylamino)tetralin; Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Dentate Gyrus - drug effects; Dentate Gyrus - physiology; Dioxanes - metabolism; Electric Stimulation; Electrical kindling; Functional Laterality; Fundamental and applied biological sciences. Psychology; Hippocampus; Hippocampus - physiology; Iodine Radioisotopes; Kindling, Neurologic - physiology; Male; Neurons - drug effects; Neurons - physiology; Piperazines - pharmacology; Piperidines - metabolism; Pyridines - pharmacology; Radioligand Assay; Rat; Rats; Rats, Sprague-Dawley; Receptor autoradiography; Receptors, Serotonin - biosynthesis; Receptors, Serotonin, 5-HT1; Receptors, Serotonin, 5-HT4; Seizures; Serotonin - metabolism; Serotonin 5‐HT1A and 5‐HT4 receptor subtypes; Serotonin Antagonists - metabolism; Serotonin Antagonists - pharmacology; Synapses - physiology; Tritium; Vertebrates: nervous system and sense organs; WAY 100,635; Animal model; 5-HT4 Serotonine receptor; Serotoninergic transmission; Rat; Kindling; Epilepsy; Rodentia; Central nervous system; Vertebrata; Dentate gyrus; Mammalia; 5-HT1A Serotonine receptor; Convulsion; Hippocampus; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.70020850.x

: 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 µg kg−1 8‐OH‐DPAT or 1,000 µg 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.