tetrodotoxin and Fever

Febrile (fever-induced) seizures (FS) are the most common form of seizures during childhood and have been associated with an increased risk of epilepsy later in life. The relationship of FS to subsequent epilepsy is, however, still controversial. Insights from animal models do indicate that especially complex FS are harmful to the developing brain and contribute to a hyperexcitable state that may persist for life. Here, we determined long-lasting changes in neuronal excitability of rat hippocampal CA1 pyramidal cells after prolonged (complex) FS induced by hyperthermia on postnatal day 10. We show that hyperthermia-induced seizures at postnatal day 10 induce a long-lasting increase in the hyperpolarization-activated current I(h). Furthermore, we show that a reduction in the amount of spike broadening and in the amplitude of the slow afterhyperpolarization following FS are also likely to contribute to the hyperexcitability of the hippocampus long term.

Topics: Action Potentials; Anesthetics, Local; Animals; Animals, Newborn; Dose-Response Relationship, Radiation; Electric Stimulation; Fever; Hippocampus; In Vitro Techniques; Male; Pyramidal Cells; Pyrimidines; Rats; Rats, Sprague-Dawley; Seizures; Tetrodotoxin

Whether brain histaminergic neurons contribute to the regulation of tracheal tone and peripheral vascular tone under hyperthermia was investigated in anesthetized rabbits. Histamine release from the rostral ventrolateral medulla (RVLM), the raphe nuclei, and the solitary nucleus of the medulla oblongata was significantly increased by hyperthermia. The increased histamine was significantly suppressed by 10(-6) M tetrodotoxin microdialyzed in each area. Tracheal pressure and mean arterial pressure were significantly decreased and increased by hyperthermia, respectively. An H(1)-receptor antagonist, 5 x 10(-6) M (+)-chlorpheniramine, bilaterally microdialyzed in the RVLM significantly enhanced histamine release in the RVLM as well as significantly suppressed tracheal dilation and pressor response caused by hyperthermia. These data indicate that histamine release in the medulla oblongata is enhanced by hyperthermia. The enhanced histamine is the neuronal origin and the cause of tracheal dilation and pressor response at least via H(1) receptors in the RVLM. Brain histaminergic neurons play important roles in tracheal tone and peripheral vascular tone via H(1) receptors in the RVLM and homeostasis on body temperature.

Topics: Animals; Blood Pressure; Body Temperature; Chlorpheniramine; Fever; Histamine; Histamine Antagonists; Histamine H1 Antagonists; Histamine Release; Hypothalamus; Medulla Oblongata; Muscle Relaxation; Muscle, Smooth; Neurons; Pressure; Rabbits; Raphe Nuclei; Solitary Nucleus; Synaptic Transmission; Tetrodotoxin; Trachea

To clarify the role of the preoptic area and anterior hypothalamus (PO/AH) on thermoregulatory system and the effects of serotonergic innervation from the median raphe nucleus (MRN) on body temperature (Tb), we perfused tetrodotoxin (TTX) solution into the PO/AH or MRN by using a microdialysis technique at different ambient temperatures (5, 23 and 35 degrees C) in freely moving rats. Tb was continuously monitored by using a telemetry system. In the MRN, perfusion of TTX solution induced significant hypothermia in the normal environment, a greater decrease in Tb during cold exposure and had no effect on Tb during heat exposure. In the PO/AH, perfusion of TTX solution induced significant hyperthermia in normal environment, a greater increase in Tb during heat exposure and had no effect on Tb during cold exposure. Our results indicate that the PO/AH regulates mainly heat loss or inhibits the loci regulating heat production. Furthermore, heat production appears to be regulated by other loci receiving serotonergic innervation from the MRN.

Topics: Animals; Anterior Hypothalamic Nucleus; Body Temperature Regulation; Cold Temperature; Fever; Hot Temperature; Hypothermia; Male; Microdialysis; Movement; Neural Pathways; Neurons; Pons; Preoptic Area; Raphe Nuclei; Rats; Rats, Wistar; Tetrodotoxin

Brain temperature of conscious freely moving rats was recorded during perfusion of the preoptic area (POA) with neuroactive compounds using the microdialysis technique. Unilateral perfusion of the POA with the sodium channel blocking agent, tetrodotoxin (1 microM), induced a pronounced hyperthermia. Of the neuroactive compounds examined, the greatest thermogenic response to local perfusion of the POA was elicited by the GABAergic agonist, muscimol. Muscimol (10, 20 and 100 microM) exhibited a dose-dependent and reversible hyperthermia. This hyperthermia was attenuated by co-perfusion with the GABAergic antagonist, bicuculline (10 microM). Muscimol-induced hyperthermia was independent of prostaglandin biosynthesis, and additive with prostaglandin E2 (10 microM)-induced hyperthermia. Prostaglandin E2-induced hyperthermia was not affected by co-perfusion with bicuculline. These data suggest the existence of two independent neurochemical systems for genesis of hyperthermia colocalized within the POA.

Topics: Analysis of Variance; Animals; Bicuculline; Body Temperature; Dinoprostone; Dose-Response Relationship, Drug; Fever; gamma-Aminobutyric Acid; Haloperidol; Male; Microdialysis; Muscimol; Perfusion; Preoptic Area; Rats; Rats, Sprague-Dawley; Sodium Channel Blockers; Tetrodotoxin; Time Factors