Lasting Increase in Serotonin 5‐HT_1A 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-[

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

“…the results obtained here are in disagreement with those in kindled rats (Cagnotto et al 1998;Watanabe et al 1998). Indeed, we observed that acutetreated rats with 1 mg/kg of 8-OH-DPAt were resistant to the 'kindling-like' prolongation of electrographic seizure duration without affecting the time of onset of the paroxystic activity.…”

“…Although this animal model has been extensively used to screen compounds for activity against limbic seizures (Stringer and Lothman 1990a) or neuromodulators (Stringer and Erden 1995) or more recently for the effect of ketogenic diet (Bough et al 2003), the antiepileptogenic and anticonvulsant role of 5-Ht and/or its receptors subtypes has not been investigated yet. the only available electrophysiological studies of 8-OH-DPAt on DG hyperexcitability have been performed in kindled rats in chronic conditions (Cagnotto et al 1998;Watanabe et al 1998), both indicating a lack of effect of 8-OH-DPAt on kindling progression (Cagnotto et al 1998) and on any other seizure parameters (Watanabe et al 1998). therefore, these data suggest that 5-Ht 1A Rs may be involved in the fine modulation of hippocampal excitability, acting in concert with other neurotransmitter systems, and their activation alone may not be sufficient to interfere with the epileptogenic process in rats.…”

“…therefore, these data suggest that 5-Ht 1A Rs may be involved in the fine modulation of hippocampal excitability, acting in concert with other neurotransmitter systems, and their activation alone may not be sufficient to interfere with the epileptogenic process in rats. nevertheless, a lasting and selective increase in 5-Ht 1A R density induced by kindling has been shown in rats, likely due to an adaptive response of granule cells to recurrent epileptic activity that might contribute to modulation of DG hyperexcitability (Cagnotto et al 1998). …”

“…As far the 8-OH-DPAt anticonvulsant effect is concerned, it is noteworthy that only high doses of the drug are effective in various tLE experimental models, such as in vivo and in vitro hippocampal seizure models (theodore 2003;Lopez-Meraz et al 2005) and kainic acid (KA)-and pentylenetetrazol (PtZ)-induced status epilepticus (SE) (Lopez-Meraz et al 2005. Scanty results exist instead of the effect of 8-OH-DPAt on DG hyperexcitability, for instance, in the DG kindling model, systemic activation of 5-Ht 1A produced no epileptic effect (Cagnotto et al 1998;Watanabe et al 1998). therefore, there is enough evidence to suggest the use of 5-Ht 1A agonists for the treatment of tLE.…”