Arginine vasopressin does not mediate heat loss in the tail of the rat

It has been reported that hypothermia induced by arginine vasopressin (AVP) is brought about by a coordinated response of reduced thermogenesis in brown adipose tissue (BAT) and increased heat loss through the tail of rats. However, it is well known that AVP is one of the strongest peripheral vasoconstrictors. Whether the AVP-induced hypothermia is associated with an increase in heat loss through the tail is questionable. Therefore, the present study assessed the relationship between the effects of AVP on tail skin temperature and the induced hypothermic response, and to determine if peripheral AVP administration increases heat loss from the tail. Core, BAT and tail skin temperature were monitored by telemetry in male Sprague–Dawley rats before and after intraperitoneal administration of AVP or vasopressin receptor antagonist. We also analyzed simultaneously of the time-course of AVP-induced hypothermic response and its relationship with changes in BAT temperature, and effect of AVP on grooming behavior. The key observations in this study were: (1) rats dosed with AVP induced a decrease in heat production (i.e., a reduction of BAT thermogenesis) and an increase of saliva spreading for evaporative heat loss (i.e., grooming behavior); (2) AVP caused a marked decrease in tail skin temperature and this effect was prevented by the peripheral administration of the vasopressin V1a receptor antagonist, suggesting that exogenous AVP does not increase heat loss in the tail of rats; (3) the vasopressin V1a receptor antagonist could elevate core temperature without affecting tail skin temperature, suggesting that endogenous AVP is involved in suppression of thermogenesis, but not mediates heat loss in the tail of rats. Overall, the present study does not support the conclusion of previous reports that AVP increased tail heat loss in rats, because AVP-induced hypothermia in the rat is accompanied by a decrease in tail skin temperature. The data indicate that exogenous AVP-induced hypothermia attributed to the suppression of thermoregulatory heat production and the increase of saliva spreading for evaporative heat loss.     

氧化震颤素在精氨酸加压素引起大鼠低温中的作用与对行为性体温调节反应的影响

目的:研究氧化震颤素在精氨酸加压素(AVP)引起低温中的作用及其对行为性体温调节反应的影响。方法:无线遥控测温技术记录成年雌性SD大鼠体核温度(Tc)、棕色脂肪组织(BAT)温度和活动的变化。用无线遥测温度梯度仪记录大鼠行为性体温调节反应。分别观察AVP(10μg/kg)和氧化震颤素(0.25 mg/kg)对大鼠Tc、活动、BAT温度(TBAT)、理毛活动和行为性体温调节反应的影响。结果:AVP和氧化震颤素均能引起Tc和TBAT降低,理毛活动增加,引起低温反应的同时动物选择较低环境温度。氧化震颤素能使AVP引起的Tc和TBAT降低,以及理毛活动的增加更明显,并持续更长时间。注射氧化震颤素后立即注射AVP动物亦选择较低环境温度,但与AVP比较无明显差异。结论:AVP引起的低温与体温调定点下移、抑制BAT产热和增加理毛活动有关。氧化震颤素可能通过影响BAT产热和行为性体温调节参与外周给AVP引起的低温过程。     

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 10 µg/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 (10 µg/kg i.p.) rapidly decreased BAT sympathetic nerve activity in control and sham-operated rats, with the greatest levels of suppression occurring at 35 min 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 (10 µg/kg i.p.) on BAT sympathetic nerve activity. The greatest level of suppression was only 20.8% occurring at 35 min 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.     

Arginine vasopressin increases glutamate release and intracellular Ca2+ concentration in hippocampal and cortical astrocytes through two distinct receptors

Arginine vasopressin (AVP), released from the CNS, plays an important role in regulating several aspects of CNS functions including aggression, anxiety, and cognition. In this study, we report a novel finding that AVP induces glutamate release from astrocytes isolated from the cerebral cortex and hippocampus. We also investigated the types of AVP receptors involved in the AVP-induced increase in glutamate release from astrocytes isolated from the hippocampus and cortex of neonatal rats. We showed that the AVP (0.1-1000 nmol/L) induced increase in glutamate release and [Ca(2+)](i) is brought about by two distinct subtypes of V(1) receptors (V(1a) and V(1b)). Our results suggested that V(1b) receptors are predominantly expressed in astrocytes isolated from the hippocampus and V(1a) receptors are solely expressed in astrocytes isolated from the cerebral cortex of neonatal rats. The results of the western blot analyses confirmed these pharmacological data. In addition, the AVP-induced increase in glutamate did not contribute to an increase in [Ca(2+)](i), as blockade of metabotropic glutamate receptors did not alter the AVP-induced increase in [Ca(2+)](i). In addition, the administration of a phospholipase A(2) inhibitor failed to alter AVP-induced [Ca(2+)](i) increase suggesting the lack of involvement of this enzyme.     

Impairment of cold-induced increase in thyroxine 5'-deiodinase activity in mouse brown adipose tissue by the intracerebroventricular administration of bombesin.

Effects of bombesin on brown adipose tissue (BAT) thyroxine (T4) 5'-deiodinase (5'D) activity and rectal temperature were examined in male mice. Immediately following an intracerebroventricular (ICV) or intravenous (IV) injection of bombesin (0.1-100 ng/animal) or vehicle (20 mM bacitracin dissolved in 0.9% saline), the mice were placed in a room at 4 degrees C or 22 degrees C for 30, 60, 120 or 240 min. The ICV injection of bombesin dose-dependently lessened cold-induced increase in BAT 5'D activity and increased hypothermia determined at 120 min of cold exposure, whereas the IV injection of bombesin was without effect. Bombesin (ICV)-induced hypothermia preceded the inhibition of BAT 5'D activity by at least 30 min at 4 degrees C. BAT 5'D activity was not affected by ICV injection of bombesin in mice kept at 22 degrees C, although the rectal temperature was significantly decreased. Bombesin thus appears to prevent cold-induced increase in T4 5'D activity in mouse BAT by its central effect. Bombesin-induced excessive hypothermia itself and/or the decrease in sympathetic tone of BAT by bombesin might decrease cold-induced increase in BAT 5'D activity.     

Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia

Mu-opioid receptor activation increases body temperature and affects cardiovascular function. In the present study, fentanyl was administered intravenously [100 mug/kg (300 nmol/kg) iv] and intracerebroventricularly [3.4 mug (10 nmol) in 10 microl icv] in urethane-chloralose-anesthetized, artificially ventilated rats. Increases in brown adipose tissue (BAT) sympathetic nerve activity (SNA) (peak, +326% of control), BAT temperature (peak, +0.8 degrees C), renal SNA (peak, +146% of control), and heart rate (HR; peak, +32 beats/min) produced by intravenous fentanyl were abolished by premamillary transection of the neuraxis but were mimicked by intracerebroventricular administration of fentanyl, which also increased arterial pressure (AP; peak, +12 mmHg). Pretreatment with the opioid antagonist naloxone (100 nmol in 10 microl icv) eliminated the intracerebroventricular fentanyl-evoked responses. Microinjection of glycine (0.5 M, 60 nl) to inhibit local neurons in the rostral raphe pallidus (RPa) selectively reversed the intracerebroventricular fentanyl-evoked increases in BAT SNA and HR, while the fentanyl-evoked excitation in RSNA, the pressor responses, and the tachycardic responses were reversed by inhibition of neurons in the rostral ventrolateral medulla (RVLM). Prior inhibition of neurons in the dorsomedial hypothalamus eliminated the intracerebroventricular fentanyl-evoked increases in BAT SNA, BAT temperature, and HR, but not those in RSNA or AP. These results indicate that activation of central mu-opioid receptors with fentanyl can elicit BAT thermogenesis and cardiovascular stimulation through excitation of the sympathetic outflows to BAT, kidney, and heart. Activation of neurons in the rostral RPa and RVLM are essential for the increases in BAT thermogenesis and renal sympathoexcitation, respectively, induced by activation of central mu-opioid receptors. BAT thermogenesis could contribute to fentanyl-evoked hyperthermia, particularly in infants where BAT plays a significant role in thermoregulation.     

血管升压素对大鼠背根神经节神经元膜的作用

为研究血管升压素(arginine vasopressin,AVP)对大鼠背根神经节(dorsal root ganglion,DRG)神经元的作用及其机制,用细胞内微电极记录技术记录离体灌流DRG神经元的膜电位。结果如下:(1)在受检的120个细胞中,大多数(81.67％)在滴加AVP后产生明显的超极化反应。(2)滴加AVP(10μmol/L)后膜电导增加约19.34％(P<0.05)。(3)灌流平衡液巾的NaCl以氯化胆碱(CH-Cl)置代和用Cd2+阻断Ca2+通道后,AVP引起超极化反应的幅值均无明显变化(P>0.05),而加入K+通道阻断剂四乙铵(TEA)后,AVP引起的超极化反应幅值明显减小(P<0.05)。(4)AVP引起的超极化反应可被AVP V.受体拈抗剂阻断。结果捉示,AVP可使DRG大多数神经元膜产生超极化,DRG神经元膜上存在AVP V,受体,且AVP引起的超极化反应是通过神经元膜上AVP V.受体介导的K+外流所致.AVP可能参与了初级感觉信息传入的调制。     

Activation of central melanocortin-4 receptor suppresses lipopolysaccharide-induced fever in rats

Activation of central melanocortin receptors (MCR) inhibits fever, but the identity of the MCR subtype(s) mediating this antipyretic effect is unknown. To determine whether selective central melanocortin receptor-4 (MC4R) activation produces antipyretic effects, the MC4R selective agonist MRLOB-0001 (CO-His-d-Phe-Arg-Trp-Dab-NH(2)) was administered intracerebroventricularly to rats treated with Escherichia coli lipopolysaccharide (LPS, 30 microg/kg ip). Treatment with MRLOB-0001 (150 ng icv) did not lower core body temperature (T(c)) in afebrile rats but did suppress LPS-induced increases in T(c) and associated decreases in tail skin temperature (T(sk)), an indicator of vasomotor thermoeffector function. In contrast, systemic treatment with MRLOB-0001 (150 ng iv) did not produce similar antipyretic effects. Coadministration of the selective MC4R antagonist HS014 (1 microg icv) blocked the antipyretic effects of MRLOB-0001. HS014 alone (1 microg icv) had no significant effect on LPS-induced increases in T(c) or decreases in T(sk) and in afebrile rats had no significant effects on T(c) or T(sk). We conclude that pharmacological activation of central MC4R suppresses febrile increases in T(c) and that inhibition of heat conservation pathways may contribute to this effect. These findings suggest that the central MC4R may mediate the long-recognized antipyretic effects of centrally administered melanocortins.     

精氨酸加压素对大鼠抗体产生和淋巴细胞增殖的上调作用

大鼠侧脑室注射１００ｎｇ精氨酸加压素（ＡＶＰ）,用ＥＬＩＳＡ法检测血中对鸡卵白 白抗原产生的ＩｇＧ抗体水平。结果显示,ＩｇＧ水平高于对照,而ＡＶＰ的Ｖ１受体阻断剂ＤＰＡＶＰ则可阻断此作用;ｉｃｖ８００ｎｇＡＶＰ,大鼠的ＳＲＢＣ溶血素 水平高于对照;ｉｃｖ１００ｎｇ、８００ｎｇＡＶＰ２ｈ后,脾淋巴细胞对ＭＴＴ产生的颜色反应均比对照增加,而ＤＰＡＶＰ可阻断之;ｉｃｖ８００ＡＶＰ２ｈ后,脾淋巴细胞对ＭＴ     

The dynamic relationship between mu and kappa opioid receptors in body temperature regulation

Previous studies demonstrated that intracerebroventricular (icv) injection of a kappa opioid receptor agonist decreased, and a mu agonist increased, body temperature (Tb) in rats. A dose-response study with the selective kappa antagonist nor-binaltorphimine (nor-BNI) showed that a low dose (1.25 nmol, icv) alone had no effect, although a high dose (25 nmol, icv) increased Tb. It was hypothesized that the hyperthermia induced by nor-BNI was the result of the antagonist blocking the kappa opioid receptor and releasing its inhibition of mu opioid receptor activity. To determine whether the Tb increase caused by nor-BNI was a mu receptor-mediated effect, we administered the selective mu antagonist CTAP (1.25 nmol, icv) 15 min after nor-BNI (25 nmol, icv) and measured rectal Tb in unrestrained rats. CTAP significantly antagonized the Tb increase induced by icv injection of nor-BNI. Injection of 5 or 10 nmol of CTAP alone significantly decreased the Tb, and 1.25 nmol of nor-BNI blocked that effect, indicating that the CTAP-induced hypothermia was kappa-mediated. The findings strongly suggest that mu antagonists, in blocking the basal hyperthermia mediated by mu receptors, can unmask the endogenous kappa receptor-mediated hypothermia, and that there is a tonic balance between mu and kappa opioid receptors that serves as a homeostatic mechanism for maintaining Tb.     

Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia

We have tested the hypothesis that nitric oxide (NO) arising from inducible nitric oxide synthase (iNOS) plays a role in hypothermia during endotoxemia by regulating vasopressin (AVP) release. Wild-type (WT) and iNOS knockout mice (KO) were intraperitoneally injected with either saline or Escherichia coli lipopolysaccharide (LPS) 10.0 mg/kg in a final volume of 0.02 mL. Body temperature was measured continuously by biotelemetry during 24 h after injection. Three hours after LPS administration, we observed a significant drop in body temperature (hypothermic response) in WT mice, which remained until the seventh hour, returning then close to the basal level. In iNOS KO mice, we found a significant fall in body temperature after the fourth hour of LPS administration; however, the hypothermic response persisted until the end of the 24 h of the experiment. The pre-treatment with beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Et-Tyr2, Val4, Arg8-Vasopressin, an AVP V1 receptor antagonist (10 microg/kg) administered intraperitoneally, abolished the persistent hypothermia induced by LPS in iNOS KO mice, suggesting the regulation of iNOS under the vasopressin release in this experimental model. In conclusion, our data suggest that the iNOS isoform plays a role in LPS-induced hypothermia, apparently through the regulation of AVP release.     

Nicotine stimulates secretion of corticosterone via both CRH and AVP receptors

Corticosterone-releasing hormone (CRH) and arginine vasopressin (AVP) are crucial components of the hypothalamic-pituitary-adrenal axis that stimulates the release of adrenocorticotropic hormone from the pituitary and mediate the stress response. CRH binds to two subtypes of CRH receptors (CRH-R1 and CRH-R2) that are present in both central and peripheral tissues. We used the CRH-R1-specific antagonist, antalarmin (ANT), the CRH-R1 and CRH-R2 peptide antagonist, astressin (AST), and the CRH-R2-specific peptide antagonist, astressin2b (AST2b), to determine which CRH receptor is involved in the nicotine-stimulated secretion of corticosterone. Male C57BL/6 mice were administered ANT (20 mg/kg, i.p.), AST (0.3 mg/kg, i.p.), AST2b (0.3 mg/kg, i.p.) or vehicle prior to administration of nicotine (1.0 mg/kg, s.c.), CRH (10 μg/kg, s.c.), AVP (10 μg/kg, s.c.) or saline (s.c.), killed 15 min later and trunk blood collected and assayed for corticosterone plasma levels. We found that CRH enhanced corticosterone release, and this response was blocked by both AST and ANT. Nicotine also increased corticosterone secretion, but this effect persisted in the presence of either CRH antagonist. Furthermore, AST but not ANT or AST2b decreased corticosterone levels associated with stress of handling and injection. We also assessed the role of AVP V(1b) -specific receptor antagonist, SSR149415 alone and in combination with AST and AST2b. Although the AVP antagonist did not alter basal or nicotine-stimulated corticosterone secretion, it attenuated the AVP-induced stimulation of corticosterone and its combination with AST but not AST2b completely abolished nicotine-mediated stimulation of corticosterone secretion. Our results demonstrate that the nicotine-induced stimulation of the hypothalamic-pituitary-adrenal axis is mediated by both the CRH-R and the AVP V(1b) receptor and when the CRH receptor is blocked, nicotine may utilize the AVP V(1b) receptor to mediate secretion of corticosterone. These results argue in favor of the development of specific antagonists that block both AVP and CRH receptors to decrease the pleasurable component of nicotine, which may be mediated by corticosterone.     

Antipyresis due to centrally administered vasopressin differentially alters thermoregulatory effectors depending on the ambient temperature

The intracerebroventricular (i.c.v.) administration of arginine vasopressin (AVP), in the febrile rat elicits an antipyresis at cold, warm and neutral ambient temperatures. These experiments were conducted, therefore, to elucidate the thermoregulatory effector mechanisms responsible for this antipyretic effect. At 25 degrees C, AVP-induced antipyresis was mediated by tail skin vasodilation while metabolic rate was unaffected. At 4 degrees C, the antipyresis produced by AVP was approximately double that seen at 25 degrees C. This effect appeared to be mediated exclusively by inhibition of heat production since the metabolic rate decreased markedly following AVP. This antipyresis at 4 degrees C was accompanied by cutaneous vasoconstriction. At 32 degrees C, neither vasomotor tone, metabolic rate nor evaporative heat loss could be shown to contribute to the small antipyretic effect elicited by AVP. We conclude from these data that i.c.v. AVP is producing antipyresis by affecting the febrile body temperature set-point mechanism since the thermoregulatory strategy to lose heat varies at different ambient temperatures and the decrease in body temperature cannot be shown to be due to changes in a single effector mechanism.     

Effect of YM471, a nonpeptide AVP receptor antagonist,on human coronary artery smooth muscle cells

The antagonistic properties of YM471, a potent nonpeptide vasopressin (AVP) V(1A) and V(2) receptor antagonist, were characterized using human coronary artery smooth muscle cells (CASMC). YM471 potently inhibited specific binding of 3H-AVP to V(1A) receptors on human CASMC, exhibiting a K(i) value of 0.49 nM. Furthermore, YM471 inhibited the AVP-induced increase in intracellular free Ca(2+) concentration with an IC(50) value of 1.42 nM, but exerted no agonistic activity on CASMC. Additionally, while AVP concentration-dependently induced hyperplasia and hypertrophy in CASMC, YM471 prevented these AVP-induced growth effects, exhibiting IC(50) values of 0.93 and 2.64 nM, respectively. These results indicate that YM471 has high affinity for V(1A) receptors on, and high potency in inhibiting AVP-induced physiologic responses of, human CASMC.     

Central vasopressin in the modulation of catecholamine release in conscious rats

Neurons containing arginine vasopressin (AVP) have been shown to project from the paraventricular nucleus of the hypothalamus to the nucleus tractus solitarius (NTS) in the medulla. We investigated whether AVP acts in brain stem regions to influence sympathoadrenal outflow. Cannulae were implanted into the fourth ventricle of rats 7 days prior to the experiment. The effects of intracerebroventricular (icv) injections of AVP, the vehicle, and AVP antagonist, d(CH2)5Tyr(Me)AVP, on mean arterial pressure (MAP) and plasma noradrenaline (NA) and adrenaline (A) levels were determined in conscious unrestrained rats. Injections of AVP (icv, 23 and 73 ng/kg) but not the vehicle increased MAP and plasma NA and A levels. In contrast, iv injection of AVP increased MAP but decreased plasma concentrations of A and NA. The pressor response to icv injection of AVP was abolished by prior icv injection of AVP antagonist. Injection of AVP antagonist (icv, 0.5 and 1.5 microgram/kg) had no effect on MAP or plasma NA or A levels. These results show that centrally injected AVP activates sympathoadrenal outflow, possibly via an inhibition of baroreceptor reflexes. Since centrally administered AVP antagonist did not influence MAP or plasma NA or A levels, it appears that endogenously released AVP does not have a tonic influence on central cardiovascular reflex system in conscious, unrestrained rats.     

Effect of a new V1 antagonist (OPC-21268) on vascular action of vasopressin in cultured rat vascular smooth muscle cells.

The effect of 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl-3,4-dihydro-2(1 H)- quinolinone) (OPC-21268) on vascular action of arginine vasopressin (AVP) was examined in cultured rat vascular smooth muscle cells (VSMC) by the measurement of cytosolic free calcium concentration [( Ca2+]i) and the AVP V1 receptor study. The preincubation of cells with OPC-21268 for 10 min inhibited the AVP-induced mobilization of [Ca2+]i in a dose-dependent manner but did not affect the angiotensin II-induced mobilization of [Ca2+]i. The receptor study revealed that OPC-21268 blocks the binding of AVP to the receptor in VSMC in a similar way to the V1 structural antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-O-methyltyrosine]AVP: d(CH2)5Tyr(Me)AVP. Lineweaver-Burk plot showed that OPC-21268 is the competitive AVP V1 receptor antagonist. These results therefore indicate that OPC-21268 specifically blocks the vascular action of AVP mediated through the competitive inhibition of AVP binding to the receptors in VSMC.     

Is visceral sympathoexcitation to heat stress dependent on activation of ionotropic excitatory amino acid receptors in the rostral ventrolateral medulla?

Acute heat stress activates visceral sympathetic nerve discharge (SND) in young rats, and the functional integrity of the rostral ventrolateral medulla (RVLM) is required for sustaining visceral sympathoexcitation during peak increases in internal body temperature (T(c)). However, RVLM mechanisms mediating SND activation to hyperthermia remain unknown. In the present study, we investigated the role of RVLM ionotropic excitatory amino acid receptors in mediating visceral SND activation to heat stress in anesthetized, young rats. The effects of bilateral RVLM kynurenic acid (Kyn; 2.7 and 5.4 nmol), saline, or muscimol (400-800 pmol) microinjections on renal SND and splenic SND responses to heat stress were determined at peak hyperthermia (T(c) 41.5°C), during progressive hyperthermia (T(c) 40°C), and at the initiation of heating (T(c) increased from 38 to 38.5°C). RVLM Kyn microinjections did not reduce renal and splenic SND recorded during progressive or peak hyperthermia and did not attenuate SND activation at the initiation of heating. In fact, renal and splenic SND tended to be or were significantly increased following RVLM Kyn microinjections at the initiation of heating and during hyperthermia (40 and 41.5°C). RVLM muscimol microinjections at 39, 40, and 41.5°C resulted in immediate reductions in SND. These data indicate that RVLM ionotropic glutamate receptors are required for mediating visceral sympathoexcitation to acute heating and suggest that acute heating activates an RVLM ionotropic excitatory amino acid receptor dependent inhibitory input, which reduces the level of visceral SND to heating.     

Micromolar concentration of kynurenic acid in rat small intestine

Kynurenic acid is an antagonist of glutamate and alpha-7 nicotinic acetylcholine receptors and an agonist of the G: -protein-coupled receptor GPR35, which is predominantly expressed in immune and gastrointestinal tissues. In this study, we report that kynurenic acid is present in the lumen of rat small intestine in micromolar concentration sufficient to affect the GPR35 receptor. Moreover, we show that kynurenic acid can be produced by Escherichia coli. We suggest that kynurenic acid may modulate gastrointestinal function and integrity.     

中枢精氨酸加压素在大鼠促肾上腺皮质激素释放激素释放激素引起发热机制中的作用

实验对大鼠进行第三脑室和脑腹中隔区插管,用数字体温计测量大鼠的结肠温度,用放射免疫分析法测定脑中隔区精氨酸加压素（arginine vasopressin,AVP）含量,观察脑中隔区AVP在大鼠促肾上腺皮质激素释放激素（corticotrophin releasing hormone,CRH）性发热机制中的作用。结果发现：脑室注射CRH（5.0μg）引起大鼠结肠温度明显升高,同时明显增高脑中隔区AVP的含量。脑腹中隔区注射AVP V1受体拮抗剂本身并不导致大鼠结肠温度明显改变,但能显著增强脑室注射CRH引起的发热反应。而且,腹中隔区注射AVP显著抑制大鼠CRH性发热。结果提示：发热时CRH是引起脑腹中隔区AVP释放的因素之一,脑腹中隔区内源性AVP抑制中枢注射CRH引起的体温升高。     

Dopamine D2-receptors mediate hypothermia in mice: ICV and IP effects of agonists and antagonists

The effect of centrally and peripherally administered dopamine D1 and D2 specific compounds on core body temperature in mice was investigated. Quinpirole (LY-17155), a D2 agonist, induced a dose-dependent fall in body temperature (2.4–11.6%; p<0.003) when injected intraperitoneally (ip, 0.3–3.0 mg/kg) and intracerebroventricularly (icv, 0.1 mg/kg). This quinpirole-induced (1.0 mg/kg, ip) hypothermia was reversed by the central and peripheral administration of the D2 antagonists S-(–)-sulpiride (3.0–30.0 mg/kg, ip; 0.1–3.0 mg/kg, icv) and spiperone (0.03 and 0.1 mg/kg, ip; 0.03–3.0 mg/kg, icv). Domperidone, a D2 antagonist which does not cross the blood brain barrier, had no effect on quinpirole-induced hypothermia (1.0–10.0 mg/kg, ip). Domperidone partially reversed quinpirole-induced hypothermia at 0.1–30.0 mg/kg, icv. The D1 agonist, SKF-38393 at a high dose of 10.0 mg/kg, ip mildly attenuated quinpirole-induced hypothermia (a 1.8% increase in temperature). SKF-38393 at 10.0 mg/kg, icv potentiated quinpirole-induced hypothermia. SCH-23390 (0.1–3.0 mg/kg, ip), a D1 antagonist, had no effect on quinpirole-induced hypothermia and potentiated the hypothermia when administered icv. An ineffective icv dose of spiperone (0.01 mg/kg) in reversing quinpirole-induced hypothermia was rendered effective by prior administration of SCH-23390 (0.1–3.0 mg/kg, icv) but not by SKF-38393 (1.0–10.0 mg/kg, icv). These data suggest a central D2 receptor mechanism mediating hypothermia in mice which is capable of being modulated by the D1 receptor.