Preoptic-anterior Hypothalamic Region Research Articles

Fifteen-minute consultation: Paediatric night sweats—when to reassure and when to investigate

3-year-old Susie has been referred to the medical paediatric clinic by her general practitioner with sweating at night; her parents change Susie’s pillowcase whilst she is asleep at around 11pm...

Lithium affects REM sleep occurrence, autonomic activity and brain second messengers in the rat

The effects of a single intraperitoneal administration of lithium, a drug used to prevent the recurrence of mania in bipolar disorders, were determined in the rat by studying changes in: (i) the wake–sleep cycle; (ii) autonomic parameters (hypothalamic and tail temperature, heart rate); (iii) the capacity to accumulate cAMP and IP 3 in the preoptic-anterior hypothalamic region (PO-AH) and in the cerebral cortex (CC) under an hypoxic stimulation at normal laboratory and at low ambient temperature ( T a). In the immediate hours following the injection, lithium induced: (i) a significant reduction in REM sleep; (ii) a non-significant reduction in the delta power density of the EEG in NREM sleep; (iii) a significant decrease in the concentration of cAMP in PO-AH at normal laboratory T a; (iv) a significant increase of IP 3 concentration in CC following exposure to low T a. The earliest and most sensitive effects of lithium appear to be those concerning sleep. These changes are concomitant with biochemical effects that, in spite of a systemic administration of the substance, may be differentiated according to the second messenger involved, the brain region and the ambient condition.

Cloning and analysis of the lamprey GnRH-III cDNA from eight species of lamprey representing the three families of Petromyzoniformes

The lamprey, which are divided into three families, including the Petromyzonidae, Geotriidae, and Mordaciidae, have been shown to regulate the reproductive axis through a functional hypothalamic–pituitary–gonadal axis. To date, two forms of gonadotropin-releasing hormone (GnRH) have been identified in the sea lamprey ( Petromyzon marinus), lamprey GnRH-I (decapeptide and cDNA) and lamprey GnRH-III (decapeptide), both of which have been shown to be expressed in the preoptic-anterior hypothalamic region and both forms have been demonstrated to regulate reproductive function (i.e. steroidogenesis and gametogenesis). The objective of this study was to isolate the cDNA encoding the prepro-lamprey GnRH-III from eight species of lamprey using a PCR based subcloning procedure. A degenerate primer designed to the lamprey GnRH-III decapeptide was used to amplify the 3′ end of each transcript, while gene specific primers were used to amplify the 5′ ends. Phylogenetic analysis using the prepro-lamprey GnRH-III amino acid sequences was performed, in which the lamprey GnRH-III sequences divided into three groups, supporting the current view of the lamprey lineage at the family level. Finally, a phylogenetic analysis of these newly identified deduced amino acid sequences together with 64 previously described GnRH sequences suggests that the lamprey GnRHs are unique, as they group together separately from the three previously described paralogous lineages of the GnRH family.

Distribution of somatostatin (SS) immunoreactivity using specific rabbit antibodies in preoptic-anterior hypothalamus (PO-AH) of female rat brain

Distribution of somatostatin (SS) immunoreactivity was observed in the preoptic-anterior hypothalamus (PO-AH) of the female rat brain. Six specific rabbit antibodies A (SS-14), B (SS-28), C (SS-28 complete), D (SS 14 and SS-28 both), E (SS preprohormone) and F (GHRH) were used for immunostaining using Avidin–Biotin Complex (ABC) method (Hsu et al., 1981). Immunostaining was observed with all the six antibodies, in the serial sections passing through various bregma levels (−0.3 to −3.3 mm) of preoptic-anterior hypothalamic (PO-AH) region including median eminence (ME). In conclusion, the present study suggests that immunoreactive nerve terminals for both SS-14 and SS-28 are present in internal (IZ) and external zones (EZ) of ME. High intensity of SS-14 and SS-28 containing terminals in EZ suggests that both SS fractions are involved in regulating GH secretion in anterior pituitary. This is a first report on comparative distribution of immunoreactivities of four different fractions of SS, SS-preprohormone and GHRH in PO-AH.

Gabaergic and cholinergic basal forebrain and preoptic-anterior hypothalamic projections to the mediodorsal nucleus of the thalamus in the cat

The present study examined projections of GABAergic and cholinergic neurons from the basal forebrain and preoptic-anterior hypothalamus to the “intermediate” part of the mediodorsal nucleus of the thalamus. Retrograde transport from this region of the mediodorsal nucleus was investigated using horseradish peroxidase-conjugated wheatgerm agglutinin in combination with peroxidase-antiperoxidase immunohistochemical staining for glutamic acid decarboxylase and choline acetyltransferase. A relatively large number of retrogradely-labelled glutamic acid decarboxylase-positive neurons are located in the basal forebrain, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. Moreover, retrogradely-labelled choline acetyltransferase-positive cells are interspersed among glutamic acid decarboxylase-positive neurons, accounting for about 6% of the total choline acetyltransferase-positive cell population in the basal forebrain. The glutamic acid decarboxylase-positive and choline acetyltransferase-positive retrogradely-labelled neurons are distributed throughout several regions of the basal forebrain, including the medial septum, the diagonal band of Broca, the magnocellular preoptic nucleus, the substantia innominata pars anterior, the substantia innominata pars posterior, and the globus pallidus where only a few retrogradely-labelled neurons were seen. The choline acetyltransferase-positive mediodorsal-projecting neurons are morphologically different from the choline acetyltransferase-positive neurons in the basal forebrain, suggesting that those projecting to the mediodorsal nucleus are a small proportion of the cholinergic neuronal population in the basal forebrain. In the preoptic-anterior hypothalamus, many retrogradely-labelled glutamic acid decarboxylase-positive cells were found, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. These retrogradely-labelled glutamic acid decarboxylase-positive neurons are distributed throughout the preoptic-anterior hypothalamus in a continuous line with those in the basal forebrain, including the lateral preoptic area, the medial preoptic area, the bed nucleus of the stria terminalis, and the anterior and dorsal hypothalamic areas. The highest percentage of mediodorsal-projecting GABAergic neurons is in the anterior lateral hypothalamus where more than 25% of the total population of glutamic acid decarboxylase-positive cells project to the mediodorsal nucleus of the thalamus. Overall, of the large population of retrogradely-labelled neurons in the basal forebrain and preoptic-anterior hypothalamus, a significant proportion are glutamic acid decarboxylase-positive neurons (>60% in the basal forebrain and >30% in the preoptic-anterior hypothalamus), while the choline acetyltransferase-positive neurons amount to a smaller percentage of the neurons projecting to the mediodorsal nucleus (<13% in the basal forebrain and <2% in the preoptic-anterior hypothalamus). These results provide anatomical evidence of direct GABAergic projections from the basal forebrain and preoptic-anterior hypothalamic regions to the “intermediate” part of the mediodorsal nucleus in the cat. This GABAergic projection field could be the direct pathway by which the basal forebrain directly modulates thalamic excitability and may also be involved in mechanisms modulating electroencephalographic synchronization and sleep through the “intermediate” mediodorsal nucleus.

Behavioural responses of laboratory rats to playback of 22 kHz ultrasonic calls

It has been demonstrated that cholinergic stimulation of the anterior hypothalamicpreoptic region induces 22 kHz ultrasonic vocalization in rats. Acoustic features of the cholinergically induced vocalization did not differ from those of 22 kHz calls emitted in natural situations and, therefore, could have a behavioural significance for other conspecifics. The 22 kHz calls induced by intracerebral injection of carbachol were played back to rats and their responses were compared with responses to playback of 22 kHz calls induced by tactile stimuli and to those with background noise. Animal responses were measured by an accelerometric sensor as an average ergometric activity. The average activity count was not changed during presentation of acoustic stimuli, however, striking differences were found in animal responses immediately after discontinuation of the sound. Activity of the rats consistently and significantly decreased after presentation of 22 kHz calls induced by tactile stimuli or by injection of carbachol. Animal responses to calls induced by carbachol were indistinguishable from responses to calls induced by tactile stimuli. No significant changes in the general activity of the animals were observed after presentation of the background noise or during the sessions without stimuli. The results demonstrate that carbachol-induced ultrasonic calls have behavioural significance for other conspecifics and could serve as an alarm call in a similar way to naturally produced 22 kHz vocalization.

Immortalized hypothalamic luteinizing hormone-releasing hormone (LHRH) neurons: a new tool for dissecting the molecular and cellular basis of LHRH physiology.

1. Two LHRH neuronal cell lines were developed by targeted tumorigenesis of LHRH neurons in vivo. These cell lines (GN and GT-1 cells) represent a homogeneous population of neurons. GT-1 cells have been further subcloned to produce the GT1-1, GT1-3, and GT1-7 cell lines. While considerable information is accumulating about GT-1 cells, very little is currently known about the characteristics and responses of GN cells. 2. By both morphological and biochemical criteria, GT-1 cells are clearly neurons. All GT-1 cells immunostain for LHRH and the levels of prohormone, peptide intermediates, and LHRH in the cells and medium are relatively high. 3. GT-1 cells biosynthesize, process, and secrete LHRH. Processing of pro-LHRH appears to be very similar to that reported for LHRH neurons in vivo. At least four enzymes may be involved in processing the prohormone to LHRH. 4. LHRH neurons are unique among the neurons of the central nervous system because they arise from the olfactory placode and grow back into the preoptic-anterior hypothalamic region of the brain. Once these neurons reach this location, they send their axons to the median eminence. With respect to the immortalized neurons, GN cells were arrested during their transit to the brain. In contrast, GT-1 cells were able to migrate to the preoptic-anterior hypothalamic region but were unable correctly to target their axons to the median eminence. These problems in migration and targeting appear to be due to expression of the simian virus T-antigen. 5. While GT-1 cells are a homogeneous population of neurons, they are amenable to coculture with other types of cells. Coculture experiments currently under way should help not only to reveal some of the molecular and cellular cues that are important for neuronal migration and axonal targeting, but they should also highlight the nature of the cellular interactions which normally occur in situ. 6. GT-1 cells spontaneously secrete LHRH in a pulsatile manner. The interpulse interval for LHRH from these cells is almost identical to that reported for release of LH and LHRH in vivo. GT-1 cells are interconnected by both gap junctions and synapses. The coordination and synchronization of secretion from these cells could occur through these interconnections, by feedback from LHRH itself, and/or by several different compounds that are secreted by these cells. One such compound is nitric oxide. 7. GT-1 cells have Na+, K+, Ca2+, and Cl- channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of extrahypothalamic neurons to short temperature transients during the ultradian wake-sleep cycle

The thermosensitivity of neurons in thaaamo-striate-limbic structures located dorsally to the classical thermosensitive anterior hypothalamic-preoptic region was studied in cats during the natural ultradian wake-sleep cycle. Direct cooling or warming of the brain tissue by means of water-perfused thermodes was combined with tonic cooling or warming of the abdominal wall using a water-perfused heat exchanger on which the animal was lying. Out of 482 neurons, 116 (24.1 %) were thermosensitive. They were located in the nuclei reticularis and ventralis anterior of the thalamus, the fundus of the caudate nucleus, the bed nucleus of the stria terminalis, the bed nucleus of the inferior thalamic peduncle, and the nucleus of the anterior commissure. Abdominal warming increased the effect of direct brain warming and decreased the effect of direct brain cooling; opposite effects were obtained by abdominal cooling. Thermosensitivity was present during wakefulness and synchronized sleep, but depressed or altered during desynchronized sleep.

Projections of GABAergic and cholinergic basal forebrain and GABAergic preoptic‐anterior hypothalamic neurons to the posterior lateral hypothalamus of the rat

Within the basal forebrain, gamma-aminobutyric acid (GABA)-synthesizing neurons are codistributed with acetylcholine-synthesizing neurons (Gritti et al. [1993] J. Comp. Neurol. 329:438-457), which constitute one of the major forebrain sources of subcortical afferents to the cerebral cortex. In the present study, descending projections of the GABAergic and cholinergic neurons were investigated to the lateral posterior hypothalamus (LHp) through which the medial forebrain bundle passes and where another major forebrain source of subcortical afferents is situated. Retrograde transport of cholera toxin b subunit (CT) from the LHp was combined with immunohistochemical staining for glutamic acid decarboxylase (GAD) and choline acetyl transferase (ChAT) using a sequential peroxidase-antiperoxidase (PAP) technique. A relatively large number of GAD+ neurons (estimated at approximately 6,200), which represented > 15% of the total population of GAD+ cells in the basal forebrain (estimated at approximately 39,000), were retrogradely labeled from the LHp. These cells were distributed through the basal forebrain cell groups, where ChAT+ cells are also located, including the medial septum and diagonal band nuclei, the magnocellular preoptic nucleus, and the substantia innominata, with few cells in the globus pallidus. In these same nuclei, a small number of ChAT+ cells were retrogradely labeled (estimated at approximately 800), which represented only a small percentage (< 5%) of the ChAT+ cell population in the basal forebrain (estimated at approximately 18,000). Both the GAD+ and ChAT+ LHp-projecting neurons represented a small subset of their respective populations in the basal forebrain, distinct from the magnocellular, presumed cortically projecting, basal neurons. In addition to the GAD+ cells in the basal forebrain, GAD+ cells in the adjacent preoptic and anterior hypothalamic regions were also retrogradely labeled in significant numbers (estimated at approximately 5,500) and proportion (> 20%) of the total population (estimated at approximately 30,000) from the LHp. The retrogradely labeled GAD+ neurons were distributed in continuity with those in the basal forebrain through the lateral preoptic area, medial preoptic area, bed nucleus of the stria terminals, and anterior and dorsal hypothalamic areas. Of the large number of cells that project to the LHp in the basal forebrain and preoptic-anterior hypothalamic regions (estimated at approximately 66,000), the GAD+ neurons represented a significant proportion (> 15%) and the ChAT+ neurons a very small proportion (approximately 2%). The relative magnitude of the GABAergic projection suggests that it may represent an important inhibitory influence of the descending efferent output from the basal forebrain and preoptic-anterior hypothalamic regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Iloprost, a stable analogue of PGI 2, potentiates the hyperthermic effect of PGE 2 in rats

Centrally mediated effects of iloprost, a stable analogue of PGI 2, on rectal temperature have been investigated in conscious rats. ICV administration of iloprost (100–1,000 ng, ICV) produced a dose-dependent, monophasic hyperthermic response that was not inhibited by indomethacin. When injected into the preoptic anterior hypothalamic (POAH) region, iloprost (2–50 ng/POAH) induced a biphasic increase in rectal temperature. While the first phase was inhibited by AH 6809, an E 1-type prostaglandin (EP 1) receptor antagonist, the second phase was abolished by indomethacin pretreatment. Iloprost was found not to alter rectal temperature when injected into the ventromedial hypothalamic area. Administration of iloprost into the POAH in a dose that had no effect on rectal temperature significantly potentiated the hyperthermic effect of PGE 2 (50 ng, ICV). These findings suggest that the pyrogenic effect of iloprost is partly mediated by EP 1 receptors located on the POAH. Regarding the similarities of iloprost and PGI 2, it is further proposed that endogenous PGI 2 might act to modulate hyperthermic effects of PGE 2 released during arachidonic acid- or endogenous pyrogen-induced fever.

Distribution of luteinizing hormone-releasing hormones I and II (LHRH-I and -II) in the quail and chicken brain as demonstrated with antibodies directed against synthetic peptides.

Polyclonal antibodies were raised in rabbits against polypeptides corresponding to the N-terminal part (heptapeptides) of the two avian gonadotropin-releasing hormones, chicken (c) LHRH-I and -II. These peptides, which were synthesized by the continuous-flow technique, were selected because they contained the smallest number of common amino acid residues. The pGlu-His-Trp-Ser sequence at the C-terminal was suppressed to avoid possible cross-reactions between the antisera. The antisera generated in this way were tested for specificity by solid and liquid phase absorption as well as by antigen spot tests. The antiserum raised against cLHRH-I recognized this peptide preferentially though not exclusively. Some cross-reaction with cLHRH-II was observed in the absorption test, although spotting tests suggested a total specificity. The anti cLHRH-II appeared to be completely specific in all tests. These two antibodies were then used to study the distribution of cLHRH-I and -II immunoreactive structures in the quail and chicken brain. cLHRH-I immunoreactive perikarya were observed in a fairly wide area covering the preoptic-anterior hypothalamic and septal region. By contrast, cLHRH-II cells were confined to a single group located in the dorsal aspects of the occulomotor nuclei, at the junction of the di- and mesencephalon. A sex difference in the number of cLHRH-I cells was detected in the anterior lateral preoptic region of the quail. Fibers immunoreactive for either cLHRH-I or cLHRH-II were widely distributed in the telencephalon, diencephalon, and mesencephalon but showed a specific pattern of anatomical localization. In particular, a high density of cLHRH-I fibers were seen in the external layer of the median eminence, while cLHRH-II fibers were less prominent at this level. Contrary to previous reports, a significant amount of cLHRH-II fibers were however seen throughout the median eminence (mostly external layer). The extensive distribution of both cLHRH-I and -II fibers in the quail and chicken brain is consistent with the potential role played by these peptides in the gonadotropin secretion and in the control of reproductive behavior. The specific role of cLHRH-II remains however elusive at present.

Long-term depressor effects of catecholamine neuronal grafts in the third ventricle of the brain in normotensive rats

Neuronal tissue containing A-6 group noradrenalin (NA) neurons of the locus ceruleus, or A-10 group dopamine (DA) neurons of the substantia nigra, was grafted into the third ventricle at the level of the preoptic-anterior hypothalamic region, in normotensive male rats. A significant and long-lasting depressor effect was shown in rats with either graft. In rats with an NA neuron-rich graft, plasma concentrations of arginine-vasopressin (AVP), plasma renin activity (PRA), and corticosterone (CS) decreased significantly, whereas in rats with a DA neuron-rich graft, AVP and PRA concentrations also decreased significantly but CS showed no significant change. Neither NA nor adrenalin in plasma changed significantly in rats with either graft.

Pyrogenicity of polyadenylic � polyuridylic acid in rabbits

Polyadenylic.polyuridylic acid injected intravenously into rabbits produced a rapid-onset, monophasic fever. Pyrogenic tolerance occurred in rabbits following daily injections of polyadenylic.polyuridylic acid. However, direct injection of the agent into the preoptic anterior hypothalamic region of rabbit's brain produced a markedly different fever. After an intrahypothalamic injection of polyadenylic.polyuridylic acid, fever was delayed in onset and persisted for a longer period. At room temperature, the fever was due to both increased metabolism and cutaneous vasoconstriction. In a colder atmosphere the fever was due solely to increased metabolism, whereas in the heat the fever was due to reduction in cutaneous blood flow and respiratory evaporative heat loss. In addition, the fever induced by intravenous polyadenylic.polyuridylic acid injection was reversed by a cyclooxygenase inhibitor, but not by a protein synthesis inhibitor. Polyadenylic.polyuridylic acid was shown to stimulate PGE2 production from rabbit's hypothalamus in vitro. The results reveal that this agent is a prostaglandin-dependent pyrogen.

In vitro release of gonadotropin-releasing hormone from the brain preoptic-anterior hypothalamic region and pituitary of female goldfish

In vitro release of gonadotropin releasing hormone (GnRH) from slices of the preoptic-anterior hypothalamic (P-AH) region and fragments of the pituitary of goldfish was studied using a static incubation system. Release of GnRH from both tissue preparations was stimulated by depolarizing concentrations of extracellular potassium ions (K +). Other putative secretagogues, calcium ionophore A21387 (1 μ M), forskolin (100 μ M), and prostaglandin E 2 1 μ M) also stimulated release of GnRH from both tissue preparations. Omission of Ca 2+, or chelating the remaining remaining Ca 2+ by EGTA (0.1 m M), abolished the release of GnRH stimulated by high K + concentrations (60 m M), but did not reduce spontaneous release. Verapamil (1 μ M), a voltage-sensitive calcium channel blocker, abolished the release of GnRH stimulated by high K + or A21387 from both tissue preparations. The GnRH released in vitro from both the P-AH region and pituitary was concentrated by Sep-Pak and then separated by high-performance liquid chromatography. The major peak of the GnRH immunoreactivity was found to coelute with synthetic salmon GnRH ([Trp 7, Leu 8]-GnRH) and the minor peak with chicken GnRH-II ([Gln 8]-GnRH). Dopamine (10 and 100 μ M) inhibited GnRH release from both P-AH slices and pituitary fragments, while serotonin (1–100 μ M) stimulated release from both. Norepinephrine (10–100 μ M) stimulated GnRH release from P-AH slices but not from pituitary fragments. The results demonstrate that the release of GnRH from goldfish P-AH slices and pituitary fragments in vitro in response to various secretagogues and monoamines can be studied using a static incubation system.

Angiotensin II Receptors in the Ventral Portion of the Bed Nucleus of the Stria terminalis

In vitro receptor autoradiography, using the radiolabeled angiotensin II (Ang II) antagonist 125I-sar1,ile8 Ang II (125I-SI Ang II; 250 pM) in the absence or presence of 1 microM Ang II, was used to identify Ang II receptor binding sites in the preoptic-anterior hypothalamic (POAH) brain region of cycling female rats. A nucleus within this region, lateral to the organum vasculosum of the lamina terminalis and ventral to the anterior commissure, displayed a discrete locus of 125I-SI Ang II binding sites (385 fmol/g tissue). This nucleus, which corresponds to the area of the POAH from which Ang II is most effective at eliciting luteinizing hormone release, has been identified as the ventral portion of the bed nucleus of the stria terminalis (BSTV) by the rat brain atlas of Paxinos and Watson. The selective nonpeptidic Ang II alpha receptor antagonist Dup 753 completely inhibited the binding of 125I-SI Ang II to the BSTV and other hypothalamic nuclei, suggesting that these receptors are of the Ang II alpha subtype.

Relationship between cAMP concentration in anterior hypothalamic-preoptic region and the ultradian wake-sleep cycle

In the rat anterior hypothalamic-preoptic region adenosine 3′:5′-cyclic monophosphate concentration changes during the ultradian wake-sleep cycle. The administration of dl-propranolol and the exposure to low ambient temperature decreased the nucleotide concentration and also modified the wake-sleep cycle. This suggests that in this region a biochemical correlation exists with different functional states.

Are separable aromatase systems involved in hormonal regulation of the male brain?

In vitro study of testosterone (T) metabolism shows that formation of estradiol-17 beta (E2) is regionally specific within the preoptic area (POA) of the male ring dove. The POA is known to be involved in the formation of E2 required for specific components of male sexual behavior. Two sub-areas of high aromatase activity, anterior (aPOA) and posterior preoptic (pPOA) areas, have been identified. Aromatase activity is higher in aPOA than in pPOA. The aromatase activity within the aPOA is also more sensitive to the inductive effects of low circulating T, derived from subcutaneous silastic implants, than the enzyme activity in pPOA. Kinetic analysis of preoptic fractions indicates that a similar high-affinity enzyme occurs in both areas (apparent Km less than 14 nM), but the Vmax of aPOA enzyme activity is higher than pPOA. Cells containing estrogen receptors (ER) are localized in areas of high aromatase activity. There is overlap between immunostained cells in the aPOA and in samples containing inducible aromatase activity measured in vitro. Within the aPOA there is a higher density of ER cells in the nucleus preopticus medialis. The pPOA area also contains ER, notably in the nucleus interstitialis, but at a lower density. We conclude that the hormonal regulation of the male preoptic-anterior hypothalamic region, which is a target for the behavioral action of T, involves at least two inducible aromatase systems with associated estrogen receptor cells.

Pyrogenicity of interferon and its inducer in rabbits

The effects of intracerebral administration of interferon (IFN) or its inducer polyriboinosinic acid-polyribocytidylic acid (poly I:C) on thermoregulatory responses were assessed in conscious rabbits. Administration of IFN (10(2)-10(6) IU) or poly I:C (0.012-12 micrograms) into the preoptic anterior hypothalamus or the third cerebral ventricle caused a dose-dependent fever in rabbits at three ambient temperatures (Ta) tested. In the cold (Ta = 8 degrees C), the fever was due to increased metabolism, whereas in the heat (Ta = 32 degrees C) the fever was due to a reduction in respiratory evaporative heat loss and ear skin blood flow. At the moderate environmental temperature (Ta = 22 degrees C), the fever was due to increased metabolism and cutaneous vasoconstriction. Compared with the febrile responses induced by cerebroventricular route injection of IFN or poly I:C, the hypothalamic route of injection required a much lower dose of IFN or poly I:C to produce a similar fever. Furthermore, the fever induced by intrahypothalamic injection of IFN or poly I:C was reduced by pretreatment of animals with a systemic dose of indomethacin (an inhibitor of all prostaglandins formation) or cycloheximide (an inhibitor of protein synthesis). The data indicate that IFN or its inducer may act through the endogenous release of a prostaglandin or a protein factor of an unknown chemical nature in the preoptic anterior hypothalamic region to induce fever in rabbits. The fever induced by IFN or its inducer is brought about by a decrease in heat loss and/or an increase in heat production in rabbits.

Interaction of propranolol with central serotonergic neurons

Central monoaminergic mechanisms are believed to be involved in cardiovascular regulation. The present study was designed to evaluate the involvement of central serotonergic pathways in the antihypertensive action of propranolol in pentobarbital anesthetized mongrel dogs. Ventriculocisternal perfusion of propranolol (25 ug/kg/min for 30 min) decreased serotonin turnover as indicated by a significant decrease in cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA). This effect was accompanied by a significant reduction in mean arterial pressure and heart rate. These results indicate that propranolol decreases central serotonergic activity and suggests a possible role for central serotonergic pathways in the antihypertensive action of propranolol. Several studies have indicated that central serotonergic pathways participate in the regulation of blood pressure (1, 2). Brainstem regions including the nucleus tractus solitarius, the raphe nucleus and the anterior hypothalamic preoptic region are involved in cardiovascular control and contain a dense population of serotonergic neurons (3,4,5). A centrally-mediated hypotensive effect of propranolol has been demonstrated. Centrally administered propranolol increases cerebrospinal fluid (CSF) levels of norepinephrine and reduces blood pressure possibly due to decreased peripheral sympathetic nerve activity (6,7). Central serotonergic pathways may also be involved in the antihypertensive action of some beta-adrenoceptor antagonists. Destruction of central serotonergic neurons with 5,7-dihydroxytryptamine and desipramine abolished the antihypertensive effect of intracisternal propranolol in sinoaortic denervated dogs (8). Acute administration of (-)-propranolol (9) and (−)-pindolol (10) decreased the synthesis rate of serotonin, while acute administration of salbutamol, a beta 2-adrenoceptor agonist, increased 5-HIAA levels in rat brain structures (11). The present study was designed to evaluate the involvement of central serotonergic pathways in the antihypertensive action of propranolol.

Thermosensitivity of anterior hypothalamic-preoptic neurons during the waking-sleeping cycle: a study in brain functional states

The thermosensitivity of anterior hypothalamic-preoptic neurons was studied in cats during the waking-sleeping cycle. Direct cooling and warming of the anterior hypothalamic-preoptic region was accomplished with water-perfused thermodes. Neuronal thermosensitivity was determined by means of the linear regression analysis of firing rate changes vs anterior hypothalamic-preoptic temperature changes. A total of 117 neurons were classified as thermosensitive during wakefulness and synchronized sleep (20.1% of the studied neurons). Cold-sensitive neurons outnumbered warm-sensitive neurons by 3.7:1. The homeothermic states, wakefulness and synchronized sleep, are characterized by similar frequency distributions of neuronal thermosensitivity, although variable changes in single neuron thermosensitivity are state-dependent. Such changes underlie the quantitative differences in homeothermic regulation between these states. The impairment of thermoregulation during desynchronized sleep is characterized by a different frequency distribution of neuronal thermosensitivity resulting from both a drop in the responsiveness to thermal stimulation of a majority of neurons and a reversal in the sensitivity to cooling and warming of a minority of neurons. In conclusion, only the frequency distribution of thermosensitivity in the neuronal population is indicative of changes in the thermoregulation paradigm across behavioral states.