Effects of midbrain raphe lesions or systemic p-chlorophenylalanine on the development of kindled seizures in rats.
Previous research has suggested that brain serotonin (5-hydroxytryptamine or 5-HT) neurons inhibit epileptiform seizure activity. To test further this possibility, experiments were performed to determine if brain 5-HT depletion would enhance the occurrence and/or magnitude of seizures "kindled" from the amygdala or neocortex of rats. Two modes of 5-HT depletion were used: (1) radiofrequency heat lesions of the midbrain dorsal and median raphe nuclei, and (2) systemic injection of the 5-HT synthesis inhibitor, p-chlorophenylalanine (pCPA). Both modes of 5-HT depletion reliably enhanced the strength of motor convulsions kindled from the cortex. Systemic pCPA also reduced the duration of after-discharges (ADs) in cortically-stimulated rats. However, pCPA reduced rather than enhanced convulsions kindled from the amygdala. In contrast to this, raphe lesions appeared to sensitize rats to the effects of amygdaloid kindling, i.e., lesions lowered AD thresholds, AD durations and number of ADs to elicit motor convulsions. Viewed together, these data support the hypothesis that 5-HT neurons can serve to inhibit seizures. However, the lack of robustness across parameters of epileptogenesis as well as discrepant findings related to 5-HT depletion mode additionally suggest that kindled seizures affect other neuronal populations in addition to those under serotonergic influence.
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000523:psychology; D012701:Serotonin / Q000502:physiology
D012701:Serotonin; D010134:Fenclonine