The hypothermic effects of dl-tetrahydropalmatine in rats.

Systemic administration of dl-tetrahydropalmatine (THP; 10-50 mg x kg(-1) intraperitoneally) produced a proportional decrease in both colonic temperature and release of hypothalamic serotonin (5-hydroxytryptamine (5-HT)) in rats at room temperature. The hypothermia was brought about by cutaneous vasodilation and decreased metabolism. The THP- induced hypothermia was significantly attenuated in rats with brain 5-HT depletion produced by control injection of 5,7-dihydroxytryptamine or in rats with 5-HT2A receptor activation produced by 1-(2,5-dimethoxy-4-iodophenyl) -2-aminopropane, or in rats with 5-HT1A receptor antagonist produced by (-)-pindolol. The results suggest involvement of serotoninergic antagonism in the THP-induced hypothermia in rats

Magnolol decreases body temperature by reducing 5-hydroxytryptamine release in the rat hypothalamus.

1. The effects of magnolol, isolated and purified from the cortex of Magnolia officinalis Rehd. et Wils, on thermoregulation and hypothalamic release of 5-hydroxytryptamine (5-HT) by in vivo microdialysis were assessed in normothermic rats and in febrile rats treated with interleukin-1 beta. 2. Intraperitoneal administration of magnolol (25-100 mg/kg) produced a decrease in colon temperature, an increase in foot skin temperature, a decrease in metabolic rate and a decrease in the endogenous release of 5-HT in the rat hypothalamus. 3. Depletion of rat brain 5-HT, produced by intracerebroventricular pretreatment with 5,7-dihydroxytryptamine, attenuated the magnolol-induced hypothermia, cutaneous vasodilation and decreased metabolism. 4. Intracerebroventricular administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine (a 5-HT2 receptor agonist; 5-10 micrograms/5 microL) increased basal colon temperature and reversed the magnolol-induced hypothermia. 5. The increases in both colon temperature and hypothalamic 5-HT release produced by interleukin-1 beta injection were attenuated by treatment with magnolol. 6. The data suggest that magnolol decreases body temperature (due to increased heat loss and decreased heat production) by reducing 5-HT release in rat hypothalamus.

Changes in extracellular serotonin in rat hypothalamus affect thermoregulatory function.

Experiments were carried out to determine the effects of altering the serotonin (5-HT) levels in the hypothalamus on thermoregulatory function in unanesthetized restrained rats. Local perfusion of the hypothalamus with dialysis solution containing 5-hydroxytryptophan (a 5-HT precursor), fluoxetine (a 5-HT reuptake inhibitor), or high potassium significantly increased both colonic temperature (Tco) and the extracellular concentrations of 5-HT in the hypothalamus. Reciprocally, both extracellular concentration of 5-HT in the hypothalamus and Tco were decreased with a dialysis solution containing tetrodotoxin (which blocks the voltage-dependent sodium channel), zero calcium concentration, or systemic administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT,5-HT1A agonist). Intrahypothalamic administration of 8-OH-DPAT and (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (a 5-HT2 agonist) produced hypothermic and hyperthermic effects, respectively. The results indicate that elevating the 5-HT levels in the hypothalamus activates postsynaptic 5-HT2 receptors and results in hyperthermic effects, whereas stimulation of presynaptic 5-HT1A receptors in the hypothalamus reduces the endogenous 5-HT release and results in hypothermic effects.

Catecholaminergic mechanisms-mediated hypothermia induced by magnolol in rats.

Intraperitoneal administration of magnolol (25-100 mg/kg) produced a dose-related fall in rats' colonic temperature. The magnolol-induced hypothermia was attenuated by pretreatment with intracerebroventricular 6-hydroxydopamine (200 microg/rat). The L-DOPA (200 mg/kg, i.p.) plus benserazide (50 mg/kg, i.p.)-induced hyperthermia was attenuated by magnolol. On the other hand, the alpha-methyltyrosine (100 mg/kg, i.p.)-induced hypothermia was potentiated by magnolol. Furthermore, magnolol (50 mg/kg, i.p.) decreased the dopamine and norepinephrine release in the hypothalamus, but did not change the concentrations for their metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). The data suggest that magnolol decreases colonic temperature by reducing catecholaminergic activity in rat hypothalamus.

Hypotensive and bradycardic effects of dl-tetrahydropalmatine mediated by decrease in hypothalamic serotonin release in the rat.

In anesthetized rats, intravenous administration of dl-tetrahydropalmatine (dl-THP, 1-10 mg/kg) elicited proportional hypotension, bradycardia and decreases in hypothalamic serotonin (5-HT) release (measured by carbon-fiber electrodes in combination with voltammetry). In addition, postsynaptic blockade of 5-HT2 receptors with cyproheptadine (2-5 mg/kg, i.v.) or ketanserin (2-5 mg/kg, i.v.) produced both hypotension and bradycardia, while stimulation of 5-HT2 receptors with 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10-250 mg/kg, i.v.) produced both hypertension and tachycardia. The dl-THP-induced hypotension and bradycardia could be reversed by DOI treatment. The data indicate that dl-THP decreases both arterial pressure and heart rate through a serotonergic release process in the hypothalamus.