Serotonin participation in the suppression of focal epileptiform activity by noxious stimulation

Thompson, Peter Maurice (1987) Serotonin participation in the suppression of focal epileptiform activity by noxious stimulation. Masters thesis, Memorial University of Newfoundland.

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Abstract

Noxious stimulation acting, at least in part, by a serotonergic mechanism suppresses penicillin-induced focal epileptiform activity in the rat (Neuman, 1986b). In the present study the site of serotonin's action and the serotonin receptor subtype involved in the process were investigated. The working hypothesis was that an increase in the cortical concentration of serotonin arising from the rostral raphe nuclei mediated the suppression of focal epileptiform activity by noxious stimulation. -- The systemic administration of agents known to inhibit raphe unit activity including serotonin agonists 8-0H-2-(di-n-propylamine) tetralin. 2-methoxyphenylpiperazine and trifluoromethylpiperazine as well as blockers of serotonin uptake, imipramine and fluoxetine, prevented the suppression of focal epileptiform activity by noxious stimulation. Analgesia at the spinal cord level was not thought to be a factor in this blockade, but rather the drugs were considered to act by inhibiting dorsal raphe neurons. -- The pressure ejection of serotonin and 8-0H-2-(di-n-propylamine) tetralin into the dorsal raphe also blocked the suppression of focal epileptiform activity by noxious stimulation, despite a several minute delay between pressure ejection of drug and response. Available histology confirmed that the majority of responsive sites were located in the dorsal raphe, while the majority of non-responsive sites were located outside the dorsal raphe region. While the involvement of the dorsal raphe was clearly established in this study, the degree of this involvement could not be determined. -- Studies at the cortical level involving the pressure ejection of 1) the serotonin precursor L-5-hydroxytryptophan in rats pretreated with p-chlorophenylalanine, and 2) the serotonin releaser p-chloroamphetamine, provided some evidence that serotonin at the cortical level was essential to the suppression of focal epileptiform activity by noxious stimulation. However, similar studies with serotonin or fenfluramine failed to show any effect. -- Serotonin antagonists with affinity for 5-HT, but not 5-HT₂ and 5-HT₁C, but not 5-HT₃ receptors, blocked the suppression of focal epileptiform activity by noxious stimulation. Based on the available data it appears that 5-HT mediates the suppression of focal epileptiform activity by noxious stimulation by an action at 5-HT₂ and/or 5-HT₁C receptors. -- Key Words -- Focal Epileptiform Activity; Serotonin; Noxious Stimulation; Dorsal Raphe; Cerebral Cortex.

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