Influences of dopamine and noradrenaline on outward potassium currents through the somatic membrane of neurons of the molluscs (Limnaea) of different ages

Dopamine- and noradrenaline-induced modifications of outward potassium currents were studied in identified neurons of the lesser parietal ganglion of adult (10–12 months) and old (22–24 months) molluscsLimnaea stagnalis. In the neurons of old molluscs, 2·10⁻⁵ M dopamine made activation of potassium channels of delayed current 2.5 times more frequent than in adult molluscs. Noradrenaline (5·10⁻⁵ M) significantly increased delayed outward potassium currents in adult molluscs and did not modify these currents in old molluscs. It is supposed that there are age-related modifications of the ratio between the active and passive components of potassium ion transport in the mechanism responsible for monoamine-induced reactions of a neuron.     

Comparison of structural and functional age changes in identified neurons of molluscLymnaea stagnalis

Experiments on adult (aged 10–12 months) and old (aged 20–22 months) molluscsLymnaea stagnalis were aimed at comparison of functional and structural changes in identified neurons of the lesser parietal ganglion. No age changes were observed in the membrane potential of a neuron, in the resistance of its membrane, or in the amplitude, duration, and rate of rise of the leading edge of the action potential. With age, thresholds for direct stimulation of a neuron increased substantially, the repolarization phase of the action potential slowed down, and the amplitude of the afterhyperpolarization decreased. The most pronounced age changes were revealed in the characteristics of background neuronal activity. A distinct correlation was observed between the frequency of background spikes in a neuron and the state of its structures, both in adult and in old individuals. In the molluscs of both age groups the neurons with a high frequency of spike generation featured high activity of the protein-biosynthesizing system. In contrast, the structure of cells with a low firing frequency in old molluscs differed significantly from that of the neurons with similar activity in adult individuals, first of all, by substantially pronounced morphological manifestations of the suppression of protein-synthesizing processes, as well as by catabolic and destructive-dystrophic changes.Neirofiziologiya/Neurophysiology, Vol. 25, No. 6, pp. 409–417, November–December, 1993.     

Ontogeny of the bovine neurohypophysial hormone precursors. III. Identification of neurohormones, neurophysins and copeptin in the early bovine fetus

Neurohypophysial hormone precursors are small proteins processed into several fragments during axonal transport from hypothalamus to neurohypophysis. From 3-month-old fetal bovine pituitaries the three fragments of vasopressin precursor, arginine vasopressin, MSEL-neurophysin and copeptin, and the two fragments of oxytocin precursor, oxytocin and VLDV-neurophysin, have been isolated and characterized. These polypeptides are identical to those previously identified in the late fetus (7-9 months old) and in the adult. It is concluded that the same genes are expressed during fetal and adult lives, the vasopressin gene appearing roughly four times more active than the oxytocin gene in the early fetus. Vasotocin, mesotocin and additional neurophysin have not been detected in the early fetus.     

Ontogeny of the bovine neurohypophyseal hormone precursors. Foetal neurohormones and neurophysins

Neurohypophyseal hormones are fragments of precursor proteins that include specific neurophysins and are processed during axonal transport. Neurohormones and neurophysins purified from 7-9 month old bovine foetuses have been characterized by amino acid analysis and partial amino acid sequences. Oxytocin and arginine vasopressin, on one hand, and VLDV-neurophysin and MSEL-neurophysin, on the other, are identical to products previously characterized in the adult. Whereas oxytocin and vasopressin genes seem to be expressed at the same rates in the adult, as judged by the amounts of their peptide products in neurohypophysis, in the late foetus the vasopressin gene appears to be roughly three times more active than the oxytocin gene.     

Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP

Insulin-regulated aminopeptidase (IRAP) is a membrane aminopeptidase and is homologous to the placental leucine aminopeptidase, P-LAP. IRAP has a wide distribution but has been best characterized in adipocytes and myocytes. In these cells, IRAP colocalizes with the glucose transporter GLUT4 to intracellular vesicles and, like GLUT4, translocates from these vesicles to the cell surface in response to insulin. Earlier studies demonstrated that purified IRAP cleaves several peptide hormones and that, concomitant with the appearance of IRAP at the surface of insulin-stimulated adipocytes, aminopeptidase activity toward extracellular substrates increases. In the present study, to identify in vivo substrates for IRAP, we tested potential substrates for cleavage by IRAP-deficient (IRAP(-/-)) and control mice. We found that vasopressin and oxytocin were not processed from the NH(2) terminus by isolated IRAP(-/-) adipocytes and skeletal muscles. Vasopressin was not cleaved from the NH(2) terminus after injection into IRAP(-/-) mice and exhibited a threefold increased half-life in the circulation of IRAP(-/-) mice. Consistent with this finding, endogenous plasma vasopressin levels were elevated twofold in IRAP(-/-) mice, and vasopressin levels in IRAP(-/-) brains, where plasma vasopressin originates, showed a compensatory decrease. We further established that insulin increased the clearance of vasopressin from control but not from IRAP(-/-) mice. In conclusion, we have identified vasopressin as the first physiological substrate for IRAP. Changes in plasma and brain vasopressin levels in IRAP(-/-) mice suggest a significant role for IRAP in regulating vasopressin. We have also uncovered a novel IRAP-dependent insulin effect: to acutely modify vasopressin.     

Circadian Activity Rhythms and Phase‐Shifting of Cultured Neurons of the Rat Suprachiasmatic Nucleus

The mammalian suprachiasmatic nucleus (SCN) is the major endogenous pacemaker that coordinates various daily rhythms including locomotor activity and autonomous and endocrine responses, through a neuronal and humoral influence. In the present study we examined the behavior of dispersed individual SCN neurons obtained from 1‐ to 3‐day‐old rats cultured on multi‐microelectrode arrays (MEAs). SCN neurons were identified by immunolabeling for the neuropeptides arginine‐vasopressin (AVP) and vasoactive intestinal polypeptide (VIP). Single SCN neurons cultured at low density onto an MEA can express firing rate patterns with different circadian phases. In these cultures we observed rarely synchronized firing patterns on adjacent electrodes. This suggests that, in cultures of low cell densities, SCN neurons function as independent pacemakers. To investigate whether individual pacemakers can be influenced independently by phase‐shifting stimuli, we applied melatonin (10 pM to 100 nM) for 30 min at different circadian phases and continuously monitored the firing rate rhythms. Melatonin could elicit phase‐shifting responses in individual clock cells which had no measurable input from other neurons. In several neurons, phase‐shifts occurred with a long delay in the second or third cycle after melatonin treatment, but not in the first cycle. Phase‐shifts of isolated SCN neurons were also observed at times when the SCN showed no sensitivity to these phase‐shifting stimuli in recordings from brain slices. This finding suggests that the neuronal network plays an essential role in the control of phase‐shifts.     

The effects of midazolam on hippocampal dentate gyrus granule neurons from young and old Fischer 344 rats

The effects of midazolam (3 nM) perfusion on the membrane and synaptic properties of dentate gyrus granule neurons were examined in hippocampal slices obtained from young adult (4-6 months) and old (24-26 months) Fischer 344 rats. In young neurons, midazolam perfusion resulted in a hyperpolarization of the resting membrane potential with no apparent change in the input resistance. Midazolam perfusion also produced a significant increase in the amplitude of the post-spike train afterhyperpolarization (AHP). In neurons obtained from old animals, midazolam perfusion also produced a hyperpolarization of the resting membrane potential but did not significantly change the AHP. These effects may result from altered calcium homeostasis in neurons of the aged brain, and suggest that at least some of the direct actions of benzodiazepines on mammalian central neurons are altered during aging.     

The involvement of voltage-operated calcium channels in somato-dendritic oxytocin release

Magnocellular neurons of the supraoptic nucleus (SON) secrete oxytocin and vasopressin from axon terminals in the neurohypophysis, but they also release large amounts of peptide from their somata and dendrites, and this can be regulated both by activity-dependent Ca(2+) influx and by mobilization of intracellular Ca(2+). This somato-dendritic release can also be primed by agents that mobilise intracellular Ca(2+), meaning that the extent to which it is activity-dependent, is physiologically labile. We investigated the role of different Ca(2+) channels in somato-dendritic release; blocking N-type channels reduced depolarisation-induced oxytocin release from SONs in vitro from adult and post-natal day 8 (PND-8) rats, blocking L-type only had effect in PND-8 rats, while blocking other channel types had no significant effect. When oxytocin release was primed by prior exposure to thapsigargin, both N- and L-type channel blockers reduced release, while P/Q and R-type blockers were ineffective. Using confocal microscopy, we found immunoreactivity for Ca(v)1.2 and 1.3 channel subunits (which both form L-type channels), 2.1 (P/Q type), 2.2 (N-type) and 2.3 (R-type) in the somata and dendrites of both oxytocin and vasopressin neurons, and the intensity of the immunofluorescence signal for different subunits differed between PND-8, adult and lactating rats. Using patch-clamp electrophysiology, the N-type Ca(2+) current density increased after thapsigargin treatment, but did not alter the voltage sensitivity of the channel. These results suggest that the expression, location or availability of N-type Ca(2+) channels is altered when required for high rates of somato-dendritic peptide release.     

Peptidomic identification and biological validation of neuroendocrine regulatory peptide-1 and -2

Recent advances in peptidomics have enabled the identification of previously uncharacterized peptides. However, sequence information alone does not allow us to identify candidates for bioactive peptides. To increase an opportunity to discover bioactive peptides, we have focused on C-terminal amidation, a post-translational modification shared by many bioactive peptides. We analyzed peptides secreted from human medullary thyroid carcinoma TT cells that produce amidated peptides, and we identified two novel amidated peptides, designated neuroendocrine regulatory peptide (NERP)-1 and NERP-2. NERPs are derived from distinct regions of the neurosecretory protein that was originally identified as a product of a nerve growth factor-responsive gene in PC12 cells. Mass spectrometric analysis of the immunoprecipitate using specific antibodies as well as reversed phase-high performance liquid chromatography coupled with radioimmunoassay analysis of brain extract demonstrated the endogenous presence of NERP-1 and NERP-2 in the rat. NERPs are abundant in the paraventricular and supraoptic nuclei of the rat hypothalamus and colocalized frequently with vasopressin but rarely with oxytocin. NERPs dose-dependently suppressed vasopressin release induced by intracerebroventricular injection of hypertonic NaCl or angiotensin II in vivo. NERPs also suppressed basal and angiotensin II-induced vasopressin secretion from hypothalamic explants in vitro. Bioactivity of NERPs required C-terminal amidation. Anti-NERP IgGs canceled plasma vasopressin reduction in response to water loading, indicating that NERPs could be potent endogenous suppressors of vasopressin release. These findings suggest that NERPs are novel modulators in body fluid homeostasis.     

Distribution and changes with age of calcitonin gene-related peptide- and substance P-immunoreactive nerves of the rat urinary bladder and lumbosacral sensory neurons

In the distal parts of the urinary tract, nerves containing calcitonin gene-related peptide (CGRP) or substance P (SP) are sensory with their cell bodies located in lumbosacral dorsal root ganglia. These two neuropeptides are recognised as being present in pelvic sensory nerves, and may be involved in the mediation of pain, stretch and/or vasodilatation. We have used indirect immunohistochemical techniques to examine the distribution and regional variation of nerves immunoreactive (-ir) for CGRP and SP in the urinary bladder and in neurons in lumbosacral dorsal root ganglia (L1-L2 & L6-S1) of young adult (3 months) and aged (24 months) male rats. Semi-quantitative estimations of nerve densities were made for CGRP-ir and SP-ir fibres innervating the dome, body and base of the urinary bladder. Quantitative studies were also used to examine the effects of age on the percentage of dorsal root ganglion neurons immunoreactive for CGRP and SP. There were very few immunoreactive axons in the dome and the overall density of innervation increased progressively towards the base of the bladder. The density of innervation in the aged rats revealed a slight reduction in CGRP and SP innervation of the detrusor muscle but was otherwise comparable to the young group. However, immunostaining of the lumbosacral dorsal root ganglia revealed that the percentage of CGRP- and SP-ir neuronal profiles showed a significant (P < 0.05) reduction from (mean +/- S.D) 44.5 +/- 2; 23.3 +/- 2 in young adult to 25.0 +/- 2.9; 14.8 +/- 1.6 in aged rats, respectively. These findings suggest that the involvement of CGRP and SP in urinary bladder innervation is relatively unchanged in old age, but their expression in dorsal root ganglion neurons is affected by age. The afferent micturition pathway from the pelvic region via these lumbosacral ganglia may be perturbed as a result.     

Immunocytochemical study of catecholaminergic neurons in grafted mesencephalon transplanted into the hypothalamus of the rat

Mesencephalic fragments from 14 day old embryonic rat brain were transplanted into the third ventricle of adult rats neonatally treated with monosodium glutamate. From two to twelve months after grafting, the implanted tissue was still present in the ventricle and contained TH immunoreactive neurons which displayed a normal appearance at ultrastructural level. While endogenous TH containing neurons were still present in dopaminergic regions of the recipient hypothalamus, grafted mesencephalic fragments could survive and develop. They contained TH immunopositive most probably dopaminergic neurons which are able, in some cases, to innervate the host brain. This model should be of interest in the study of neuroendocrine functions of dopaminergic neurons.     

Activity-dependent feedback modulation of spike patterning of supraoptic nucleus neurons by endogenous adenosine

Neuropeptide secretion from the dendrites of hypothalamic magnocellular supraoptic nucleus (SON) neurons contributes to the regulation of neuronal activity patterning, which ultimately determines their peptide output from axon terminals in the posterior pituitary gland. SON dendrites also secrete a number of other neuromodulators, including ATP. ATP degrades to adenosine in the extracellular space to complement transported adenosine acting on pre- and postsynaptic SON A1 receptors to reduce neuronal excitability, measured in vitro. To assess adenosine control of electrical activity in vivo, we made extracellular single-unit recordings of the electrical activity of SON neurons in anesthetized male rats. Microdialysis application (retrodialysis) of the A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT) increased phasic vasopressin cell intraburst firing rates progressively over the first 5 s by 4.5 +/- 1.6 Hz (P < 0.05), and increased burst duration by 293 +/- 64% (P < 0.05). Hazard function plots were generated from interval interspike histograms and revealed that these effects were associated with increased postspike excitability. In contrast, CPT had no effect on the firing rates and hazard function plot profiles of continuously active vasopressin and oxytocin cells. However, CPT significantly increased clustering of spikes, as quantified by the index of dispersion, in oxytocin cells and continuously active vasopressin cells (by 267 +/- 113% and 462 +/- 67%, respectively, P < 0.05). Indeed, in 4 of 5 continuously active vasopressin cells, CPT induced a pseudophasic activity pattern. Together, these results indicate that endogenous adenosine is involved in the local control of SON cell activity in vivo.     

Effects of right atrial distension on the activity of magnocellular neurons in the supraoptic nucleus

A small balloon placed at the junction of the superior vena cava and right atrium was used to stimulate cardiac volume receptors in pentobarbital sodium-anesthetized male rats. Extracellular recordings were obtained from antidromically identified vasopressinergic and oxytocinergic neurosecretory cells of the supraoptic nucleus. Cells were considered sensitive to the stimulus if balloon inflation resulted in a 30% change in firing frequency. Balloon inflation that did not stretch the caval-atrial junction had no significant effect on vasopressin neurons (n = 51, P > 0.05). Stretch of the caval-atrial junction decreased the firing activity in 64 of 83 putative vasopressin neurons (P < 0.01 compared with control). Stretch of the caval-atrial junction influenced the firing activity of only 3 of 26 antidromically activated oxytocinergic neurons, an effect not statistically different from control (P > 0. 05). When bilateral vagotomy was performed while recording from vasopressin neurons (n = 5), sensitivity to stretch of the caval-atrial junction was eliminated. Cardiac receptors located at the junction of the superior vena cava and right atrium may be important in regulating the activity of vasopressinergic but not oxytocinergic neurons of the supraoptic nucleus.     

Localization and osmotic regulation of vesicular glutamate transporter-2 in magnocellular neurons of the rat hypothalamus

In this report we present immunocytochemical and in situ hybridization evidence that magnocellular vasopressin and oxytocin neurons in the hypothalamic supraoptic and paraventricular nuclei express type-2 vesicular glutamate transporter, a marker for their glutamatergic neuronal phenotype. To address the issue of whether an increase in magnocellular neuron activity coincides with the altered synthesis of the endogenous glutamate marker, we have introduced a new dual-label in situ hybridization method which combines fluorescent and autoradiographic signal detection components for vasopressin and vesicular glutamate transporter-2 mRNAs, respectively. Application of this technique provided evidence that 2% sodium chloride in the drinking water for 7 days produced a robust and significant increase of vesicular glutamate transporter-2 mRNA in vasopressin neurons of the supraoptic nucleus. The immunocytochemical labeling of pituitary sections, followed by the densitometric analysis of vesicular glutamate transporter-2 immunoreactivity in the posterior pituitary, revealed a concomitant increase in vesicular glutamate transporter-2 protein levels at the major termination site of the magnocellular axons. These data demonstrate that magnocellular oxytocin as well as vasopressin cells contain the glutamatergic marker vesicular glutamate transporter-2, similarly to most of the parvicellular neurosecretory neurons examined so far. The robust increase in vesicular glutamate transporter-2 mRNA and immunoreactivity after salt loading suggests that the cellular levels of vesicular glutamate transporter-2 in vasopressin neurons are regulated by alterations in water–electrolyte balance. In addition to the known synaptic actions of excitatory amino acids in magnocellular nuclei, the new observations suggest novel mechanisms whereby glutamate of endogenous sources can regulate magnocellular neuronal functions.     

老年猫视皮层细胞对刺激反应的对比敏感度下降伴随皮层内抑制作用减弱(英文)

对人类和动物的心理学研究证实,老年个体的视觉对比敏感度相对青年个体显著下降。为揭示其可能的神经机制,采用在体细胞外单细胞记录技术研究青、老年猫(Felis catus)初级视皮层(primary visual cortex,V1)细胞对不同视觉刺激对比度的调谐反应。结果显示,老年猫V1细胞对视觉刺激反应的平均对比敏感度比青年猫显著下降,这与灵长类报道的研究结果相一致,表明衰老影响视皮层细胞对视觉刺激反应的对比敏感度是灵长类和非灵长类哺乳动物中普遍存在的现象,并可能是介导老年性视觉对比敏感度下降的神经基础。另外,与青年猫相比,老年猫初级视皮层细胞对视觉刺激的反应性显著增强,信噪比下降,感受野显著增大,表明衰老导致的初级视皮层细胞对视觉刺激反应的对比敏感度下降伴随着皮层内抑制性作用减弱。     

Expression of the long form of the prolactin receptor in magnocellular oxytocin neurons is associated with specific prolactin regulation of oxytocin neurons

Magnocellular neurons of the supraoptic (SON) and paraventricular nuclei (PVN) show considerable plasticity during pregnancy and lactation. Prolactin receptors (PRL-R) have been identified in both these nuclei. The aim of this study was to investigate the cell type(s) expressing mRNA for the long form of prolactin receptor (PRL-R(L)) and to determine whether patterns of expression change during pregnancy and lactation. In addition, we examined effects of prolactin on excitability of oxytocin and vasopressin neurons. Sections from brains of nonpregnant, pregnant, and lactating rats were hybridized with an 35S-labeled probe to label PRL-R(L) mRNA together with digoxigenin-labeled probes to detect either oxytocin or vasopressin mRNA. In the SON, PRL-R(L) mRNA was predominantly colocalized with oxytocin mRNA, with over 80% of oxytocin neurons positive for PRL-R(L) mRNA. Very few (<10%) vasopressin neurons expressed PRL-R(L) mRNA. In the PVN, PRL-R(L) mRNA was also predominantly found in oxytocin neurons, and the proportion of PRL-R(L)-positive oxytocin neurons increased significantly during pregnancy and lactation. As in the SON, relatively few vasopressin cells contained PRL-R(L) mRNA. For in vivo electrophysiology, nonpregnant rats were anesthetized, and then extracellular single neuron activity was recorded in identified oxytocin and vasopressin neurons. After a period of baseline recording, the effect of prolactin (1 microg i.c.v.) on firing rate was examined. Prolactin treatment of nonpregnant rats induced a significant decrease in firing rates of oxytocin neurons. There was no effect of prolactin on the activity of vasopressin neurons. Together, these data provide strong evidence that prolactin directly and specifically regulates activity of oxytocin neurons.     

Excitatory action of the bird antidiuretic hormone vasotocin on neurons in the subfornical organ

The responsiveness of spontaneously active neurons in the subfornical organ (SFO) of adult ducks to angiotensin II (ANGII) and the bird specific anti-diuretic hormone, arginine vasotocin (AVT), the analog of the mammalian arginine vasopressin (AVP), were investigated in brain slices with extracellular recording technique. 65% (n = 66) of the neurons increased their activity after superfusion with ANGII, the rest were unresponsive. Application of AVT activated 52% (n = 68) of the investigated neurons and like ANGII never caused an inhibition of the spontaneously active SFO neurons. A close correlation exists between the ANGII and AVT sensitivity of duck SFO neurons, because 29 out of 33 neurons were excited by AVT as well as ANGII. The relatively weak antagonistic effect of the V₁-type receptor antagonist Pmp-Tyr (Me)-Arg⁸-vasopressin on the AVT induced excitation suggests a different pharmacology of the bird AVT receptor as compared to the mammalian AVP receptor. The excitatory response of ANGII and AVT on the very same neurons suggest a similar function of both peptides on SFO mediated effects in vivo, such as an increase in water intake. However, peripheral AVT concentrations, unlike ANGII concentrations in the blood are not high enough to activate SFO neurons from the blood side of the blood brain barrier. Therefore AVT is presumably released from synapses of neurons originating within or projecting to the SFO. The identity of the ANGII and AVT reactive neurons suggests that synaptically released AVT should facilitate SFO mediated drinking.Abbreviations _a CSF artificial cerebrospinal fluid - ANGII angiotensin II - AVT arginine vasotocin - AVP arginine vasopressin - ADH antidiuretic hormone - SFO subfornical organ - AVP _4–9 arginine-vasopressin fragment 4–9 - BBB blood-brain barrier     

Peptidergic transmission in the brain. V. Systemic correlates of central activation.

Inhibition of the hippocampus by the medial amygdala is mediated by vasopressin-like peptide. Because vasopressin has action on the periphery as well as the brain, we conducted experiments to evaluate the relationship between possible peripheral actions and the central effects of the endogenous peptide. In the acutely anesthetized rat, peptide-mediated inhibition of the hippocampus is not associated with significant changes in heart rate, blood pressure or body temperature. Peripheral injections of peptide agonist fail to evoke the central inhibition, and peripheral injections of peptide antagonist fail to block the central inhibition. Stimulation of central nuclei that contain vasopressin or a similar peptide also fail to duplicate the effect of stimulating the amygdala. We conclude that the peptidergic transmission is independent of peripheral causes or correlates.     

A model for the study of the oral administration of peptide hormones.

The intragastric administration of lysine vasopressin (LVP) to rats is used as a model to study the biological activity of orally administered peptide hormones. Using a modification of the antidiuretic assay of Sawyer, LVP given by stomach tube caused a significant antidiuresis that was dose dependent in doses of 300 to 2000 mU. The simultaneous administration of the protease inhibitor, Trasylol, increased the antidiuretic effect of LVP. The synthetic peptide (1-deamino, 4 valine)-8-D-arginine-vasopressin also caused a dose-dependent prolonged and significant antidiuresis. No pressor effect was observed after intragastric administration of LVP in doses up to 40 U/rat. We are now using this model to test other procedures for enhancing the activity of lysine vasopressin administered in the gastrointestinal tract such as encapsulation into liposomes. The information gained with vasopressin will then be applied to insulin with the ultimate goal of making oral administration practical.     

Vasopressin and fever: evidence supporting the existence of an endogenous antipyretic system in the brain

Vasopressin administered into the ventral septum exerts a dose-related antipyresis. This site of action is similar in a number of species. The fever-reducing properties of vasopressin are both site and neuropeptide specific. Evidence supporting a role for endogenous vasopressin in fever suppression is the demonstration that the release of the peptide from the ventral septal area is altered during fever: the amount released correlates negatively with febrile changes in body temperature. In addition, changes in the concentration of vasopressin in the septum and amygdala have been demonstrated immunocytochemically during fever: an activation of vasopressinergic neurons occurs which is similar to that observed in pregnant animals at term when fever is absent. Specific antibodies directed against vasopressin or specific vasopressin antagonist analogues (e.g., d(CH2)5Tyr(Me)AVP) enhanced the febrile response to a pyrogen challenge when injected into the ventral septum. The same antagonist also can antagonize the antipyretic effect of exogenously administered vasopressin. The use of relatively specific antagonists and agonists of vasopressin, directed against the V1 and V2 subtypes of the peripheral vasopressin receptor, suggests that the central receptor responsible for the antipyretic effect of vasopressin may resemble the V1 subtype. Recent experiments using electrophysiological techniques have demonstrated the existence of thermoresponsive units in the ventral septal area whose activity may be altered by vasopressin which is possibly derived from the paraventricular nucleus and bed nucleus of the stria terminalis.(ABSTRACT TRUNCATED AT 250 WORDS)