Arginine vasopressin differentially modulates GABAergic synaptic transmission onto temperature-sensitive and temperature-insensitive neurons in the rat preoptic area.

The preoptic area (POA) of the hypothalamus, containing temperature-sensitive and temperature-insensitive neurons, plays a key role in specific thermoregulatory responses. Although arginine vasopressin (AVP) has been shown to induce hypothermia by increasing the firing activities of warm-sensitive neurons and decreasing those of cold-sensitive and temperature-insensitive neurons, the effects of AVP on POA GABAergic transmission remain unknown. Herein, inhibitory postsynaptic currents (IPSCs) of temperature-sensitive and temperature-insensitive neurons in POA slices were recorded using whole-cell patch clamp. By monitoring changes in GABAergic transmission during AVP treatment, we showed that AVP decreased the amplitudes and frequencies of spontaneous IPSCs in mostly warm-sensitive neurons and in some temperature-insensitive neurons but increased these parameters in other temperature-insensitive neurons. The IPSC amplitude was reduced for only cold-sensitive neurons. RT-PCR and Western blot analyses further confirmed the POA expression of V1a receptors and GABAA receptors, including the subunits α1, α2, α3, ß2, ß3 and γ2. The effects of AVP on IPSCs in temperature-sensitive and temperature-insensitive neurons were dependent on G proteins and intracellular Ca2+ . AVP-mediated modulation was associated with changes in the kinetic parameters (decay time, 10-90% rise time, half-width). Together, these results suggest that AVP, acting via V1a receptors but not V1b receptors, differentially modulates GABAergic synaptic transmission and fine-tunes the firing activities of temperature-sensitive and temperature-insensitive neurons in the rat POA.

Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats.

Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E2 (PGE2) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE2 on warm-sensitive neurons, and reversed the excitatory effect of PGE2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V1a receptor antagonist, suggesting that V1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE2-induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE2-induced increase in that in low-slope temperature-insensitive neurons through the V1a receptor. Together, these data indicated that AVP antagonized the PGE2-induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE2-induced change in the prepotential of these neurons in a V1a receptor-dependent manner.

Sinoaortic denervation attenuates vasopressin-induced hypothermia and reduction of sympathetic nerve activity innervating brown adipose tissue in rats.

It is well known that sympathetic nerve activity innervating brown adipose tissue (BAT sympathetic nerve activity) plays an important role in BAT thermogenesis. We have found that peripheral administration of arginine vasopressin (AVP) induced hypothermia by reduced thermogenesis in BAT. However, little is known about AVP-induced hypothermic response and its relationship with BAT sympathetic nerve activity. Because increases in baroreceptor inputs inhibit peripheral sympathetic nervous activity, we hypothesized that AVP-induced hypothermia is related to baroreceptor reflex suppression of BAT sympathetic nerve activity. To test this hypothesis, Male Sprague-Dawley rats were subjected to sinoaortic denervation or sham denervation, and implanted with radiotelemetry transmitters to assess the effects of peripheral administration of AVP on BAT sympathetic nerve activity, core and BAT temperatures. In sham-operated rats, an intraperitoneal (i.p.) injection of 10µg/kg AVP led to a significant decrease in core and BAT temperatures. However, sinoaortic denervation significantly reduced the fall of core and BAT temperatures induced by AVP, compared with levels in sham-operated rats. AVP (10µg/kg i.p.) rapidly decreased BAT sympathetic nerve activity in control and sham-operated rats, with the greatest levels of suppression occurring at 35min and these lowest levels attained were with 30.6% and 29.24%, respectively. Furthermore, we found that sinoaortic denervation attenuated the suppressive effects of AVP (10µg/kg i.p.) on BAT sympathetic nerve activity. The greatest level of suppression was only 20.8% occurring at 35min after AVP. Therefore, these results indicate that the hypothermic effects of peripheral administration of AVP are partially mediated by the arterial baroreceptor reflex suppression of BAT sympathetic nerve activity and BAT thermogenesis.

[Effects of 5-HT1A receptor antagonist on ethanol induced hypothermia and behavioral thermoregulatory response in rats].

OBJECTIVE: To observe the effects of 5-HT1Areceptor antagonist p-MPI on ethanol induced hypothermia and behavioral ther-moregulatory response in rats. METHODS: Core temperature and motor activities were monitored in undisturbed male SD rats using radioteleme-try. The behavioral thermoregulatory response and core temperature were monitored in rats using radiotelemetric temperature gradient apparatus. The rats were placed in a temperature gradient that permitted the selection of ambient temperature ranging from 15℃ to 40℃. Effect of ethanol (3 g/kg) and 5-HT1A receptor antagonist p-MPPI(1 mg/kg) on core temperature, motor activities, and the behavioral thermoregulatory re-sponse were observed in rats. RESULTS: ①Ethanol led to a rapid reduction in core temperature. The hypothermic responses were accompanied with a preference for cooler ambient temperature. ②5-HT1A receptor antagonist attenuated the hypothermia induced by ethanol, and accompa-nied with a selection for warmer ambient temperature. CONCLUSIONS: ①Behavioral thermoregulatory observations suggested that the ethanol could decrease the thermoregulatory set point,because rats treated with ethanol selected cooler ambient temperature facilitates the reduction in core temperature.②5-HT might be involved in ethanol-induced hypothermia and behavioral thermoregulatory response.

[Inhibitory effects of agmatine on stress-induced hyperthermia in rats].

OBJECTIVE: To examine whether agmatine (AGM) would alter stress-induces hyperthermic response. METHODS: Sixty-one male SD rats were randomly divided into three experiments. Each experiment was divided into control group and AGM group. During the experiments, the animals were maintained in a chamber at 22℃. ①Effects of intraperitoneal injecting 40 or 80 mg/kg AGM on normal core temperature and activity were observed in undisturbed rats using radiotelemetry (n=8). ②Stress-induced hyperthermia model was established by placing rats in an open-field chamber for 60 min. Rats were dosed intraperitoneally with AGM or saline, and placed immediately inside the open-field chamber. Core temperature and motor activity were monitored by radiotelemetry in an open-field chamber (n=7~8). ③Effect of AGM on energy metabolism was measured by Columbus Oxymax Lab Animal Monitoring System (n=7). RESULTS: ①Rats administered with 80 mg/kg AMG showed significant hypothermic responses (-0.46±0.11)℃, while 40 mg/kg AMG had no significant effect on the normal core temperature. ②Core temperature of control group increased by (0.78±0.16)℃ during open-field exposure, whereas rats administered 40 and 80 mg/kg AGM underwent a (0.34±0.11)℃ and (0.81±0.14)℃ reductions in core temperature within 60 min, respectively. ③Oxygen consumption and energy metabolism were significantly reduced by AGM (80 mg/kg). CONCLUSIONS: The data demonstrated that AGM induced hypothermic responses in rats and reversed stress-induced hyperthermia, and its effect might attribute to the suppression of energy metabolism.

[Role of oxotremorine in arginine vasopressin-induced hypothermia and its effects on behavioral thermoregulatory response in rats].

OBJECTIVE: To investigate the role of oxotremorine in arginine vasopressin (AVP)-induced hypothermia and its effects on the behavioral thermoregulatory response. METHODS: Core temperature (Tc), brown adipose tissue (BAT) temperature and motor activities were monitored in undisturbed female SD rats using radiotelemetry. The behavioral thermoregulatory response was monitored in rats using radiotelemetric temperature gradient apparatus. Effect of AVP (10 microg/kg) and oxotremorine (0.25 mg/kg) on Tc, motor activities, BAT temperature (T(BAT)), grooming activities and the behavioral thermoregulatory response were observed in rats. RESULTS: Administration of AVP and oxotremorine caused a significant drop in Tc, T(BAT), and an increases in grooming activities, respectively. The hypothermic responses were accompanied with a preference for cooler ambient temperature. Oxotremorine augmented the reduction of Tc, T(BAT), and the elevation of grooming activities resulting from AVP, and lasting a longer time. Administration of oxotremorine followed immediately by AVP injection in rats was also shown to induce a preference for cooler ambient temperature, but there was no significant difference compared with AVP. CONCLUSION: AVP-induced hypothermia was related with the set point temperature reduction, inhibiton of BAT thermogenesis and an increases in grooming activities. Oxotremorine could participate in peripheral AVP-induced hypothermia by affecting BAT thermogenesis and behavioral thermoregulation.

[Simultaneous telemetric analyzing of the temporal relationship for the changes of the circadian rhythms of brown adipose tissue thermogenesis and core temperature in the rat].

OBJECTIVE: To measure simultaneously the time course for the circadian rhythm of brown adipose tissue(BAT) thermogenesis and core temperature, and analyzing their temporal relationship. METHODS: The circadian rhythm of core temperature (Tc), BAT temperature (T(BAT)), axillary temperature (Tax) and motor activity were simultaneously measured by telemetry in adult male Sprague-Dawley rats at an ambient temperature of 22 degrees C during a 12-h light:12-h dark photoperiod (lights on at 06:00 h and lights off at 18:00 h). RESULTS: (1) T(BAT) was 0.67 degrees C lower than Tc group under the light phase, but it was similar to that Tc during the dark phase. The rate of increase in T(BAT) was higher than corresponding increases in Tc at the start of transition from the light to dark phase, and increase in T(BAT) commenced approximately 8 min before Tc increases. Whereas at the start of transition from the dark to light phase, decrease in T(BAT) commenced approximately 4 min before Tc decreases. (2) The amplitude of the circadian Tax rhythm was similar to that of Tc. During either the light phase or dark phase, Tax was lower than simultaneous measurement of Tc. (3) Increases in behavioral activity commenced before increases in T(BAT) and Tc at the start of transition from the light to dark phase. CONCLUSION: BAT thermogenesis contributes to increase in core temperature during the dark phase, indicating that circadian changes of BAT thermogenesis does indeed play significant role in the overall maintenance of the circadian rhythm of core temperature.

Physostigmine-induced hypothermic response in rats and its relationship with endogenous arginine vasopressin.

AIMS: It is well known that physostigmine (PHY) and other anticholinesterase (anti-ChE) agents induce hypothermia in rodents but little is known about the mechanism of action. Because arginine vasopressin (AVP) has been found to be an endogenous antipyretic molecule in the CNS, we determined if PHY-induced hypothermia is linked to the endogenous release of AVP. MAIN METHODS: Core temperature and motor activity were monitored by telemetry in rats maintained at an ambient temperature of 25 degrees C. Tail skin temperature was also measured at 30min intervals to estimate nonevaporative heat loss. The central cholinergic antagonist, scopolamine (1mg/kg; ip) and an AVP V(1) receptor antagonist (30microg/kg; ip) were administered during the period of PHY (200microg/kg; sc) induced hypothermia at 10am. Plasma AVP concentration and plasma cholinesterase (ChE) activity were measured at 50min after administration of PHY or scopolamine, respectively. KEY FINDINGS: PHY led to a rapid reduction in core temperature concomitant with a marked increase in heat loss from the tail. The hypothermic response of PHY was blocked by the AVP V(1) receptor antagonist. Administration of scopolamine also reversed the hypothermic responses and led to marked elevations in motor activity. Plasma AVP levels increased markedly at 50min after PHY and plasma ChE activity was significantly reduced by PHY. SIGNIFICANCE: The results clearly demonstrate that PHY-induced hypothermia was blocked by the AVP V(1) antagonist and associated with elevations in plasma AVP, suggesting a novel role for AVP in the mechanism of action of anti-ChE agents.

[Inhibitory effect of soman on stress induced hyperthermia in rats and the influence of central and peripheral cholinergic antagonists].

AIM: To determine the effect of soman on stress induced hyperthermia and the influence of central and peripheral cholinergic antagonists. METHODS: Effects of subcutaneous injection of soman, scopolamine, methylscopolamine and pyridostigmine on stress-induced hyperthermia were observed in rats by radio telemetry in an open-field environment. Plasma cholinesterase (ChE) activity was measured by a spectrophotometry. RESULTS: (1) Core temperature of the control group increased by 0.96 degrees C when exposed to open-field, whereas core temperature only increased by 0.55 degrees C in soman treated animals. Scopolamine, a central cholinergic antagonist, nearly abolished inhibitory effects of soman on core temperature when exposed to open-field. Methylscopolamine, a peripheral cholinergic antagonist, coadministered with soman reduced significantly the hyperthermic response to open-field exposure compared with rats dosed with soman. (2) Pyridostigmine, a peripheral anti-ChE agent that caused a 52% decrease in plasma ChE activity led to a significant enhancement of the hyperthermic response to open-field exposure. Methyl scopolamine nearly abolished the effects of pyridostigmine on stress-induced hyperthermia response. CONCLUSION: Inhibitory effect of soman on the open field hyperthermia suggested that soman treatment hampered the ability of the rat to develop a normal hyperthermic response when placed in the open-field environment. Its inhibitory effects were mediated primarily through a central muscarinic pathway. In addition, peripheral cholinergic nerve was involved in the control of stress hyperthermic response.

[Effects of central and peripheral administration of a nitric oxide synthase inhibitor on AVP-induced hypothermia in rats].

AIM: To explore the role of nitric oxide (NO) in arginine vasopressin (AVP)-induced hypothermia. METHODS: Colonic temperature was measured at 30 min intervals with a digital thermometer. Effects of central and peripheral administration of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on AVP-induced hypothermia were observed in rats. RESULTS: (1) Intravenous injection (i.v.) of AVP (4 microg x kg(-1)) and L-NAME (30 mg x kg(-1)) produced a significant drop in body temperature, respectively. Coadministration of L-NAME i.v. with AVP i.v. did not significantly influence the magnitude of AVP-induced hypothermia. (2) Intracerebroventricular (i.c.v.) injection of L-NAME (1 mg x kg(-1)) caused a significant increase in body temperature, but when the treatments with AVP and L-NAME were combined, i.c.v. injection of L-NAME markedly blocked the hypothermic effect of AVP intravenous injection. CONCLUSION: Endogenous NO in the central nervous system plays a major role in AVP-induced hypothermia. In addition, central NO seems to play a tonic thermoregulatory role by reducing normal body temperature because an increase in body temperature was observed after treatment with NOS inhibitor L-NAME.

Peripheral cholinergic pathway modulates hyperthermia induced by stress in rats exposed to open-field stress.

Exposure to an open field is psychologically stressful and leads to an elevation in core temperature (T(c)). Methyl scopolamine (MS), a muscarinic antagonist, and pyridostigmine (PYR), a carbamate that inhibits acetylcholinesterase, do not cross the blood-brain barrier and have little effect on T(c) in resting, nonstressed animals. However, we have found that MS has an antipyretic effect on T(c) that is caused by handling and cage-switch stress. PYR should act pharmacologically to reverse the effects of MS. To this end, we assessed the effects of MS and PYR on stress-induced hyperthermia. Male Sprague-Dawley rats at 90 days of age were housed individually at an ambient temperature of 22 degrees C. T(c) and motor activity were monitored by radiotelemetry in an open-field chamber. Rats were dosed intraperitoneally at 1200 with 1.0 mg/kg MS, 0.1 mg/kg PYR, a combination of MS and PYR, or saline and placed immediately inside the open-field chamber for 60 min. Stress-induced hyperthermia was suppressed immediately by MS and enhanced by PYR. T(c) only increased by 0.3 degrees C in the MS-treated animals. The hyperthermic response in the PYR group was nearly 0.6 degrees C above that of rats dosed with saline. Coadministration of PYR and MS led to a stress-induced hyperthermia response nearly identical to that of rats injected with saline. Overall, open-field stress exacerbated the effects of MS and PYR on body T(c) and provides support for a peripheral cholinergic mechanism that mediates stress-induced hyperthermia.