M. T. Lin

Cerebral ischemia is the main cause for the onset of heat stroke syndrome in rabbits

During the onset of heat stroke, rabbits displayed hyperthermia (42.8°C), and decreased cerebral perfusion pressure and decreased cerebral blood flow (as reflected by a prolonged cerebral circulation time) compared to those of normothermic rabbits. On the other hand febrile rabbits, during the fever plateau did not show the above responses, although they had a similar level of hyperthermia (42.4°C). The data support the concept that cerebral ischemia is the main cause for the onset of the heat stroke syndrome.

A modularized infrared light matrix system with high resolution for measuring animal behaviors

The current study provides a new modularized infrared light matrix system (about

The hypothalamic somatostatinergic pathways mediate feeding behavior in the rat

200 cost) which is designed to measure the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, freezing time, and total distance traveled in rats. The system records the sequences of animals activity in a computer-aided system with a resolution of 0.2 s in time or 1.6 cm in space, and permanently stores all the resulting data in file. The behavioral apparatus was tested for its sensitivity and usability by amphetamine-injected rats. It was found that intraperitoneal administration of amphetamine (1.25-2.50 mg/kg), but not normal saline, produced a dose-related increase in either the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, or total distance traveled. However, amphetamine injections produced a dose-related decrease in freezing time. Apparently, most of the amphetamine-induced responses obtained by other detecting apparatus can be reproduced easily by the present apparatus. The current detection system possesses the following advantages: a) high resolution, b) high expansion potential, and c) precise and simplified algorithms for behavioral parameter analysis.

5-Hydroxytryptamine receptors in the hypothalamus mediate thermoregulatory responses in rabbits.

The level of somatostatin in the hypothalamus was higher in satiated rats than in hungry rats. Elevating hypothalamic somatostatin levels by administering somatostatin into the hypothalamus produced a decrease in food intake, whereas lowering hypothalamic somatostatin levels by administering cysteamine into the peritoneal cavity produced an increase in food intake in rats.

Stimulation of the nigrostriatal dopamine system inhibits both heat production and heat loss mechanisms in rats

Summary1. The effects of microinjection of 5-hydroxytryptamine (5-HT) or its antagonists methysergide (a 5-HT1 receptor antagonist), cyproheptadine (a mixed 5-HT1/5-HT2 receptor antagonist), or ketanserin (a 5-HT2 receptor antagonist) into the preoptic anterior hypothalamus on thermoregulatory responses were assessed in conscious rabbits at different ambient temperatures (Ta). 2. Intrahypothalamic injection of 5-HT caused dose-dependent hypothermia in rabbits when the Ta was 2°C and 22°C. At 2°C the hypothermia was due to decreased metabolism, whereas at 22°C the hypothermia was due to increased peripheral blood flow and increased respiratory evaporative heat loss. 3. In contrast, administration of either cyproheptadine, methysergide or ketanserin into the 5-HT-sensitive sites in the preoptic anterior hypothalamus caused dose-dependent hyperthermia in rabbits when the Ta was 2°C, 22°C and 32°C. At 2°C the hyperthermia was due to increased metabolism, whereas at 32°C the hyperthermia was due to decreased peripheral blood flow and decreased respiratory evaporative heat loss. At 22°C, the hyperthermia was due to increased metabolism and decreased peripheral blood flow. 4. For a given intrahypothalamic dose (e.g.15–20 μg), either methysergide, cyproheptadine or ketanserin produced the same degree of rectal temperature elevation (e.g. about 1.4°C) in rabbits. Thus, there did not appear to be any association between hypothalamic 5-HT receptor types and thermoregulation. 5. However, the present results suggest that hypothalamic 5-HT receptors mediate thermoregulatory responses in the rabbit. Activation of hypothalamic 5-HT receptors decreases heat production and increases heat loss, whereas inhibition of hypothalamic 5-HT receptors increases heat production and decreases heat loss in the rabbit.

Depletion of hypothalamic norepinephrine reduces the fever induced by polyriboinosinic acid: polyribocytidylic acid (Poly I:Poly C) in rats

SummaryThe effects of stimulating the pars compacta of the substantia nigra (SNC) on thermoregulation were assessed in normal rats, in rats with chemical lesion of the SNC dopamine (DA) pathways and in rats with striatal DA receptor blockade. Electrical stimulation of the SNC produced hypothermia, decreased metabolism and/or cutaneous vasoconstriction in rats at ambient temperatures (Ta) below 22°C, as well as hyperthermia and cutaneous vasoconstriction in rats at Ta of 30°C. Microinjection of an excitotoxic amino acid (kainic acid) at the same brain sites also produced the same thermal responses. In vivo voltammetric studies revealed that electrical or chemical stimulation of the SNC produced an increase in striatal DA release. The enhanced striatal DA release induced by SNC stimulation was attenuated in rats after selective destruction of the nigrostriatal DA pathway by administration of 6-hydroxydopamine into the medial forebrain bundle. In addition, the magnitude of the thermal responses produced by the SNC stimulation in the cold was attenuated by selective bilateral destruction of the nigrostriatal DA pathways or selective blockade of the striatal DA produced by intrastriatal infusion of haloperidol, a DA receptor antagonist. The results indicate that stimulation of the SNC inhibits both heat production and heat loss mechanisms in the rat.

Suppression of natural killer cell activity in mouse spleen lymphocytes by several dopamine receptor antagonists

Administration of either Poly I:Poly C (0.05–0.50 μg) or norepinephrine (2–8 μg) into the anterior hypothalamic area produced a dose-related fever in rats. The fever induced by Poly I:Poly C was attenuated after selective depletion of norepinephrine in the hypothalamus. However, selective depletion of hypothalamic norepinephrine did not affect the fever induced by intrahypothalamic norepinephrine. The data indicate that Poly I:Poly C may act to induce fever through the endogenous release of norepinephrine from the rats hypothalamus.

Hypothalamic somatostatin may mediate endotoxin-induced fever in the rat

The effects of dopaminergic receptor inhibitors such as thiothixine (D1/D2), fluphenazine (D1/D2), trifluoperazine (D1/D2), pimozide (D2), flupenthixol (D1/D2), (+/−)-SKF 83566 (D1), and spiperone (D2) on splenic natural killer (NK) cell cytotoxic activities were assessed in vitro using mouse spleen lymphocytes or enriched NK cells. Both the activities of the splenic NK cell cytotoxicity and the effector-target cell conjugation were suppressed by thiothixine, fluphenazine, and trifluoperazine at concentrations from 2.64 to 14.78 μM. In addition, the augmentation of the cytolytic activity of NK cells induced by interferon-α or interleukin-2 was antagonized by pretreatment with these neuroleptic compounds. However, neither the splenic NK cell cytotoxicity nor the effector-target cell conjugation were affected by treatment with other neuroleptic compounds such as pimozide, flupenthixol, (+/−)-SKF 83566, and spiperone. Thus, it appears that neuroleptic compounds such as thiothixine, fluphenazine, and trifluoperazine may act through the mechanisms other than a dopaminergic pathway to affect the NK cell-target cell interaction.

Changes in central serotoninergic transmission affect clonidine analgesia in monkeys.

Summary(1) The changes in rectal temperature produced by an injection of a bacterial endotoxin piromen (10–40 ng in 1.0 μl) or somatostatin-14 (SS-14; 0.1–0.3 pg in 1.0 μl) into the preoptic anterior hypothalamic area were assessed and compared in control rats, in rats with hypothalamic SS depletion, and in rats with hypothalamic SS receptor blockade. (2) Intrahypothalamic injection of either piromen or SS-14 produced a dose-related rise in rectal temperature in intact, control rats. The fever induced by intrahypothalamic injection of piromen or SS-14, as well as that induced by intraperitoneal injection of piromen, was antagonized by pretreatment of the hypothalamus with a SS-14 receptor antagonist (0.1 ng in 1.0 μl) in rats. (3) On the other hand, intraperitoneal administration of cysteamine (30–100 mg/kg), in addition to producing a dose-related fall in rectal temperature, also caused a dose-related fall in hypothalamic SS-levels in rats. Furthermore, the fever induced by intrahypothalamic injection of piromen, but not SS-14, was antagonized by depletion of hypothalamic SS levels with an intraperitoneal dose of cysteamine (30 mg/kg). (4) The results indicate that a somatostatinergic pathway in the hypothalamus may mediate endotoxin-induced fever in the rat.

Insulin acts on the hypothalamic glucose-facilitated neurons to induce hyperglycemia and hyperinsulinemia in the rat

Summary1. The effects of changes in central serotoninergic transmission on clonidine analgesia were assessed in monkeys. The minimum electrical current required for producing jaw opening is referred to as the pain threshold. Pain was induced by electrical stimulation of tooth pulp afferents. 2. In the first series of studies, intracerebroventricular administration of clonidine (5–30 μg) produced dose-dependent analgesia in monkeys. The clonidine-induced analgesia was abolished or attenuated by prior injection of the animals with p-chlorophenylalanine or 5,7-dihydroxytryptamine into the third cerebral ventricle. On the other hand, pretreatment of the animals by injecting 5-HT or its precursor 5-hydroxytryptophan into the cerebral ventricle potentiated the clonidine-induced analgesia in monkeys. 3. In the second series of experiments, administration of clonidine (1–10 μg) into the diencephalic periventricular gray (of the anterior hypothalamic portion), the periaqueductal gray, or the dorsal raphe nuclei also produced dose-dependent analgesia in monkeys. The analgesia induced by clonidine injection into the diencephalic periventricular gray or the periaqueductal gray was effectively antagonized by pretreatment of the animals by injecting two 5-HT receptor antagonists (such as ketanserine and methysergide) into the diencephalic periventricular gray or the periaqueductal gray. The clonidine-induced analgesia in monkeys was not affected by pretreatment of the animals with injections of either ketanserine or methysergide into the dorsal raphe nuclei. 4. The results suggest that the functional activity of central 5-HT neurons correlate well with the analgesic sensitivity of clonidine microinjected centrally. In addition, the analgesia induced by clonidine microinjected into the diencephalic periventricular gray or the periaqueductal gray was mediated by the 5-HT receptors at the site of injection.