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Effects of triiodothyronine on 5-HT(1A) and 5-HT(1B) autoreceptor activity, and postsynaptic 5-HT(1A) receptor activity, in rat hypothalamus: lack of interaction with imipramine.

Triiodothyronine (T3) is effective in both augmenting and accelerating the therapeutic response to antidepressant drugs, especially tricyclics, and there is evidence from both human and animal studies that it acts on serotonergic neurotransmission. In this work we examined the effects of T3 alone and together with imipramine on 5-HT levels in the hypothalamus and on 5-HT(1A) and 5-HT(1B) autoreceptor sensitivity, using in vivo microdialysis in the rat. The effects of T3 on postsynaptic 5-HT(1A) receptor activity in the hypothalamus were also determined using a neuroendocrine challenge procedure. T3 administered daily at 20 microg/kg s.c. for 2 weeks reduced the sensitivity of 5-HT(1A) autoreceptors which control 5-HT release, as measured by the effect of 8-OH-DPAT to decrease 5-HT in the hypothalamus, and also the sensitivity of hypothalamic 5-HT(1B) receptors as measured by the effect of the 5-HT(1B) receptor agonist CP 93129 to decrease 5-HT release. Imipramine at 10 mg/kg daily for 4 weeks by osmotic minipump reduced 5-HT(1A) autoreceptor activity, as measured by the effect of 8-OH-DPAT in the hypothalamus, but the combination of T3 and imipramine given for 2 weeks did not affect either 5-HT(1A) or 5-HT(1B) autoreceptor activity. T3 at 20 microg/kg s.c. given daily for 1 week also reduced the sensitivity of postsynaptic 5-HT(1A) receptors in the hypothalamus, as measured by injection of 8-OH-DPAT and determination of the plasma ACTH and corticosterone responses. Animals which received T3 for 7 days showed a dose-dependent reduction in plasma free T4 levels but no change in total T3 levels. We conclude that while T3 alone affects both presynaptic and postsynaptic components of the serotonergic system, these effects may not be responsible for the therapeutic acceleration action seen with a combination of a tricyclic drug and T3.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Ontogenetic development, sexual differentiation, and effects of Aroclor 1254 exposure on expression of the arylhydrocarbon receptor and of the arylhydrocarbon receptor nuclear translocator in the rat hypothalamus.

Interaction of polychlorinated biphenyls (PCBs) with the aryl hydrocarbon receptor (AhR)/nuclear translocator (ARNT) system might interfere with the mechanisms controlling the sexual differentiation of the developing hypothalamus. The aim of this study was to evaluate the presence of AhR/ARNT in brain cells and the developmental profile of their expression in the hypothalamus of male and female rats during the perinatal period. Brain accumulation of the main PCB congeners after prenatal exposure to Aroclor 1254 and its influence on hypothalamic expression of AhR/ARNT was also assessed. The results show that: (a) AhR and ARNT are expressed both in neurons and in glia; (b) AhR expression progressively increases in the developing hypothalamus particularly in males, while ARNT is relatively constant in both sexes; (c) the prenatal administration of Aroclor to dams produces a differential accumulation of PCBs, depending on the chlorine atom number, and stimulates AhR expression only in the male hypothalamus. In conclusion, the developing male hypothalamus might be more sensitive to disrupting potential of PCBs.

Animals↗

Regional differences in feeding and other behaviors elicited by N-methyl-D-aspartic acid in the rodent hypothalamus: a reverse microdialysis mapping study.

Regional differences in the feeding stimulatory actions of hypothalamically delivered N-methyl-D-aspartate (NMDA) were investigated. NMDA (660 microM intraprobe) delivered by reverse microdialysis into the tuberal lateral hypothalamus (tLH) reliably elicited feeding in satiated rats. The average food intake was 8.6 g in 50 min, and during the infusion rats spent 26% of the time eating, compared to less than 1% before NMDA treatment. In contrast, NMDA did not affect feeding when reverse dialyzed into the anterior LH (aLH), posterior LH (pLH) or the medial hypothalamus (MH). NMDA had no apparent behavioral effect in the aLH; in contrast, it significantly decreased the time spent resting/sleeping when infused into each of the other three areas tested. Additionally, in the medial hypothalamus, NMDA infusions increased time spent grooming; while in the pLH only alertness was significantly increased. These data underscore the functional and anatomical heterogeneity of the hypothalamus, and implicate glutamate and NMDA receptors in different portions of the hypothalamus in the control of eating, grooming and arousal.

Animals↗

Functional effects of chronic electroconvulsive shock on serotonergic 5-HT(1A) and 5-HT(1B) receptor activity in rat hippocampus and hypothalamus.

The aims of this work were to determine the influence of chronic electroconvulsive shock (ECS) on presynaptic 5-HT(1A) receptor function, postsynaptic 5-HT(1A) receptor function in hippocampus and hypothalamus, and presynaptic 5-HT(1B) receptor function in hippocampus and hypothalamus. This represents part of an on-going study of the effects of ECS on serotonergic receptor activity in selected brain areas which may be relevant to the effects of electroconvulsive therapy (ECT) in humans. Chronic ECS reduced the ability of the 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetraline (8-OH-DPAT) (0.2 mg/kg s.c.) to decrease 5-HT levels in hypothalamus as shown by in vivo microdialysis, indicative of a reduction in sensitivity of presynaptic 5-HT(1A) autoreceptors. The ability of the 5-HT(1B) receptor antagonist GR 127935 (5 mg/kg s.c.) to increase 5-HT levels in both hippocampus and hypothalamus was unaffected by chronic ECS. 8-OH-DPAT (0.2 mg/kg s.c.) increased cyclic AMP levels in hippocampus measured by in vivo microdialysis approximately 2-fold. The degree of stimulation of cyclic AMP formation was not altered by chronic ECS. However the cyclic AMP response to forskolin (50 micro M) administered via the microdialysis probe, which was approximately 4-fold of basal in sham-treated rats, was almost completely abolished in ECS-treated rats. Since this indicates that either adenylate cyclase catalytic unit activity or Gs protein activity is reduced in the hippocampus after chronic ECS, the lack of change in 8-OH-DPAT-induced cyclic AMP formation may be taken as possible evidence of an increase in sensitivity of postsynaptic 5-HT(1A) receptors in the hippocampus by chronic ECS. Chronic ECS increased basal plasma levels of corticosterone, ACTH and oxytocin. The ACTH response to s.c. injections of 0.2 mg/kg or 0.5 mg/kg 8-OH-DPAT was reduced by chronic ECS. Postsynaptic 5-HT(1A) receptor activity in the hypothalamus, in contrast to the hippocampus, thus appears to be desensitized after chronic ECS. We conclude that chronic ECS has regionally specific effects on both pre- and post-synaptic 5-HT(1A) receptors, but, in contrast to some antidepressant drugs, does not affect presynaptic 5-HT(1B) receptor activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Characterization of the neuropeptide Y5 receptor in the human hypothalamus: a lack of correlation between Y5 mRNA levels and binding sites.

Neuropeptide Y (NPY) is a 36-amino-acid peptide that appears to play a central role in the control of feeding behavior. Recently, a cDNA encoding a novel NPY receptor subtype (Y5) was cloned from the rat and human hypothalamus, and shown to have a pharmacology consistent with NPY-induced feeding. We have subsequently cloned this cDNA from human hypothalamus and stably expressed it in CHO cells. Consistent with earlier reports, hY5 has a high affinity for NPY, [Leu31, Pro34]NPY, and NPY(3-36), but low affinity for larger C-terminal deletions of NPY and BIBP3226. High levels of hY5 mRNA were found in the human testis, brain, spleen and pancreas, with lower levels in several other tissues. In the human brain, hY5 mRNA levels were typically higher than hY2, but lower in comparison to hY1 receptor mRNA. To quantify the relative amounts of hY1, hY2 and hY5 mRNA in the human hypothalamus, we employed competitive RT-PCR. Interestingly, the relative amount of hY5 mRNA was substantially higher than either hY1 or hY2. However, pharmacological characterization of NPY binding sites in human hypothalamus membranes revealed predominantly the hY2 subtype. These data establish that while hY5 mRNA levels are very high in the human hypothalamus, conventional radioligand binding techniques do not detect hY5-like binding site. Whether hY5-like binding sites exist in the other human tissues that express hY5 mRNA (and what function hY5 has in those tissues) awaits future investigation.

Animals↗

Evidence for sexual dimorphism of estrogen receptors in hypothalamus and thymus of neonatal and immature Wistar rats.

It is hypothesized that the rat thymus is sexually differentiated. To begin testing this, we used the 5-day-old rat, whose hypothalamus is sexually differentiated during this period. Cytosolic estrogen receptors (ER) were measured in cytosols prepared from the brain, thymus and uterus of Wistar rats at 5, 18 and 30 days post-partum. ER concentrations were significantly higher in hypothalamus in cytosols of female 5-day-old rats, and this difference had disappeared by day 18. The pattern in thymus was identical to that observed in hypothalamus, suggesting the presence in the thymus of the aromatase system that converts androgen to estrogen, and that estrogen-mediated sexual differentiation of thymus might be proceeding at 5 days. Unlike the case for hypothalamus, no experimental model exists at present for testing functional sexual differentiation in thymus. Therefore we tested the effects of aromatase inhibitors on estrogen receptor activity in thymus well after the five-day period, and before atrophy of the thymus has commenced. Male and female rats were implanted at 15 days of age with SILASTIC implants containing 5 mg of estradiol or with 25 mg of the aromatase inhibitor 4-hydroxyandrostenedione (4-OHA) and cytosolic ER prepared at 30 days and activity measured. Administration of estradiol resulted in failure to detect available receptor, suggesting that the binding components measured were ER. After 4-OHA administration, ER concentrations were significantly increased in cytosols from male but not female hypothalamus and thymus. There is therefore a basis for exploring further the hypothesis that rat thymus is sexually differentiated.

Age Factors↗

Alternate cadmium exposure differentially affects amino acid metabolism within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats.

This work was designed to analyze the possible changes in glutamate, aspartate and glutamine content induced by cadmium exposure in the hypothalamus, striatum and prefrontal cortex of rats, using an alternate schedule of metal administration. Pubertal-adult differences were also evaluated. In adult control rats, glutamate and aspartate contents in the anterior hypothalamus decreased as compared to pubertal controls. After cadmium administration from day 30 to 60 of life, the content of anterior hypothalamic glutamate and aspartate diminished. In adult control animals, the glutamine content increased in mediobasal hypothalamus as compared to pubertal controls. After cadmium exposure from day 30 to 60 of life, the mediobasal glutamine content increased, and after cadmium treatment from day 60 to 90 of life, the mediobasal aspartate content decreased. In adult control rats the content of glutamine, glutamate and aspartate of the posterior hypothalamus decreased significantly. After cadmium administration in pubertal animals, posterior hypothalamic contents of glutamine, glutamate and aspartate diminished. Cadmium treatment of adult animals caused a decrease in glutamine content, as compared to controls. In adult control rats, only glutamate and aspartate content increased in the prefrontal cortex as compared to the values found in pubertal controls. When cadmium was administered to adult animals, only the aspartate content decreased. In the striatum, cadmium decreased the glutamine and aspartate contents when administered from day 60 to 90 of life. These data suggest that cadmium differentially affects amino acid metabolism in the hypothalamus, striatum and prefrontal cortex. Age-dependent effects of cadmium on these brain areas appeared to have occurred.

Aging↗

Quantitation of polyamines in hypothalamus and pituitary of female and male developing rats.

The quantitation of four polyamines in hypothalamus and pituitary is studied in male and female developing rats using an improved high-performance liquid chromatography method. In the hypothalamus, putrescine (PUT) reaches the highest concentration (nmol/mg protein) on day 6. It shows the lowest value in comparison with any other polyamine. Spermidine (SPD) is high during the first postnatal days. Spermine (SPM) fluctuates, and agmatine (AGM) is highest during the first week. SPD, SPM and AGM are lower in females. In the pituitary, PUT, SPD and AGM are high during the first week. SPM remains constant and it is higher in males. AGM is higher in males only on day 1. PUT shows the lowest concentration of all. Concentrations of PUT, SPD and SPM are higher in the pituitary; AGM is higher in the hypothalamus. alpha-Difluoromethylornithine (a specific and irreversible inhibitor of ornithine decarboxylase) decreases PUT and SPD, increased SPM and AGM remain unchanged in the hypothalamus and pituitary. Thus, each polyamine has its own pattern in hypothalamus and in pituitary during development in males and females; these changes could be related to the hypothalamic control of pituitary secretion of hormones related to reproduction in mammals.

Agmatine↗

Nitric oxide production in hypothalamus of 2-deoxy-D-glucose-treated and food deprived mice.

Nitric oxide (NO) has been suggested to be involved in the regulation of food intake. In the present study, NO metabolite (nitrite and nitrate, NOx) levels in the hypothalamus were determined in hyperphagic mice. In normal mice, NOx levels were higher in the hypothalamus than those in frontal cortex. Although 2-deoxy-D-glucose (2-DG) is known to induce hyperphagia by inhibiting glucose utilization, it did not affect NOx levels in the hypothalamus of mice. NOx concentration in the hypothalamus decreased in 48 h-food deprived mice. In the frontal cortex, neither 2-DG nor food deprivation affected NOx levels. These results suggest that NO production in the hypothalamus does not increase in 2-DG-elicited hyperphagia and that food deprivation reduces hypothalamic NO, probably by inhibiting NO synthase.

Animals↗

Atrial natriuretic factor does not affect norepinephrine catabolism in rat hypothalamus and adrenal medulla.

We have previously reported that atrial natriuretic factor (ANF) increases neuronal uptake and endogenous content of norepinephrine (NE) and diminishes neuronal release, synthesis and turn-over of NE in rat hypothalamus and adrenal medulla. The aim of the present work was to study another aspect of NE metabolism and therefore investigate the possible effects of ANF on NE catabolism. The determination of monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) activity and deaminates metabolites formation were studied in vitro in rat hypothalamus and adrenal medulla slices. Results showed that, in the hypothalamus, 100 nM ANF diminished MAO activity while 10 nM ANF did not modify the enzyme activity. Conversely, 10 and 100 nM ANF reduced MAO activity in adrenal medulla. On the other hand, the atrial factor modified neither COMT activity nor the formation of deaminates metabolites in the hypothalamus and adrenal medulla. Present results as well as previous findings support a putative role for ANF in the modulation of NE metabolism not only in the hypothalamus but also in the adrenal medulla of the rat, affecting the storage, release and uptake of NE but not its catabolism.

Adrenal Medulla↗

Interleukin-1 beta in the hypothalamus potentiates feline defensive rage: role of serotonin-2 receptors.

The neurochemistry of aggression and rage has largely focused on the roles played by neurotransmitters and their receptor mechanisms. In contrast, little attention has been given to the possible functions of other substances. Interleukin-1beta is an immune and brain-derived cytokine that is present in the hypothalamus. Functionally, interleukin-1 has been shown to induce the release of serotonin (5-HT), a neurotransmitter known to potently affect aggression and rage behavior. Thus, the goal of the present study was to test the hypothesis that interleukin-1beta in the medial hypothalamus could modulate defensive rage behavior in the cat. In the first experiment, electrical stimulation of sites in the medial hypothalamus from which defensive rage could be elicited and where microinjections of specific compounds were later placed, facilitated defensive rage elicited from the periaqueductal gray (PAG), thus demonstrating the functional relationship between these two regions. In the second experiment, microinjections of relatively low doses of interleukin-1beta into the medial hypothalamus potentiated defensive rage behavior elicited from the midbrain periaqueductal gray in a dose-related manner. In the third experiment, pretreatment with a selective 5-HT2 receptor antagonist, LY-53857, blocked the facilitating effects of interleukin-1beta upon defensive rage. These findings reveal for the first time that brain cytokines can dramatically alter aggressive behavior. In particular, interleukin-1beta in the medial hypothalamus potentiates defensive rage behavior elicited from the periaqueductal gray in the cat, and the potentiating effects of interleukin-1beta on this form of emotional behavior are mediated via a 5-HT2 receptor mechanism.

Animals↗

Localisation of P2X2 receptor subunit immunoreactivity on nitric oxide synthase expressing neurones in the brain stem and hypothalamus of the rat: a fluorescence immunohistochemical study.

A large body of evidence suggests that nitric oxide (NO) and ATP act as neurotransmitters in the regulatory mechanisms concerning several autonomic functions at the level of both the hypothalamus and the brain stem. In the present study, we investigated whether neuronal NO synthase containing neurones also express P2X(2) receptor subunit of the ATP-gated ion channel via double-labelling fluorescence immunohistochemistry. Our data demonstrate that a high percentage of neuronal NO synthase-immunoreactive neurones are also P2X(2)-immunoreactive in the rostral ventrolateral medulla (98%) and supraoptic nucleus of the hypothalamus (92%). Significant numbers of neuronal NO synthase-immunoreactive neurones are also P2X(2)-immunoreactive in the subpostremal (48%) and commissural (65%) subdivisions of the nucleus tractus solitarius. In the caudal ventrolateral medulla and raphe obscurus, 96% and 89%, respectively, of neuronal NO synthase containing neurones also express P2X(2) receptor subunit. In contrast to the supraoptic nucleus, there was a lower percentage of co-localisation between NO synthase and P2X(2) receptor subunit in the paraventricular nucleus of the hypothalamus. In summary, this study demonstrates for the first time that there is a widespread co-localisation of neuronal NO synthase and P2X(2) receptor subunit in the hypothalamus and brain stem of the rat. Further studies are required to elucidate whether NO and ATP functionally interact within the hypothalamus and the brain stem.

Animals↗

Dopamine turnover in the mediobasal hypothalamus in rat fetuses.

In this study, the dopamine turnover in the mediobasal hypothalamus, the key compartment of the neuroendocrine regulation of reproduction, was evaluated in fetal male and female rats. High-performance liquid chromatography with electrochemical detection was used to measure 3,4-dihydroxyphenylalanine, dopamine and 3,4-dihydroxyphenylacetic acid in the mediobasal hypothalamus of fetuses on the 21st day of intrauterine development and in primary cell culture (cell extracts and culture medium) of the same brain region, explanted at the 17th fetal day and maintained for seven days. The same technique was applied to determine dopamine release from fetal neurons of the mediobasal hypothalamus in response to an excess of K+ in the perifusion system or in culture. L-3,4-Dihydroxyphenylalanine, dopamine and 3,4-dihydroxyphenylacetic acid were detected both ex vivo and in culture. The ratios of the concentrations of L-3,4-dihydroxyphenylalanine/dopamine and 3,4-dihydroxyphenylacetic acid/dopamine were significantly higher in vitro than ex vivo, showing a lower rate of dopamine production and a higher rate of its degradation in the experiments in vitro. Moreover, it has been demonstrated that an excess of K+, i.e. a membrane depolarization, resulted in a highly increased release of dopamine in the perifusion system and in culture. The dopaminergic activity in the developing mediobasal hypothalamus showed sexual dimorphism that was manifested in a greater concentration of 3,4-dihydroxyphenylalanine and dopamine, at least in cell extracts of cultures, as well as in a higher rate of dopamine release, both in the perifusion system and in culture in males compared to females. Thus, dopamine is synthesized and released in response to a membrane depolarization in the mediobasal hypothalamus of rats as early as the end of intrauterine development, suggesting its contribution to the inhibitory control of pituitary prolactin secretion.

3,4-Dihydroxyphenylacetic Acid↗

Stress-induced stimulation of pituitary POMC gene expression is associated with activation of transcription factor AP-1 in hypothalamus and pituitary.

The response to environmental stimuli such as stress involves changes in gene transcription in both brain and pituitary, which in turn, facilitate adaptive phenotypic alterations favoring survival. In the present study we have examined the expression of the inducible immediate-early genes of the fos and jun families, and the activity of transcription factor AP-1 in the hypothalamus and anterior pituitary gland of rats, after a single restraint challenge. Restraint led to a rapid transient increase in c-fos but not c-jun expression in hypothalamus and pituitary. Changes in jun-B expression in hypothalamus were qualitatively similar to c-fos, though not statistically significant at 30 min. Furthermore, a single episode of restraint stress led to significant increases (50-100%) in nuclear AP-1 DNA binding activity in both hypothalamus and pituitary, while DNA binding of an unrelated transcription factor (Sp1) was unchanged. Associated with the stress-induced activation of pituitary AP-1 was a parallel three- to fourfold transcriptional stimulation of pituitary POMC gene expression. These data demonstrate that the rapidly inducible members of the fos and jun gene families contribute to increased activity of transcription factor AP-1 in both hypothalamus and pituitary following stress, and suggest that AP-1 may be a crucial factor involved in rapid transcriptional responses during stress.

Animals↗

New central projections of neuropeptide FF: colateral branching pathways in the brainstem and hypothalamus in the rat.

Neuropeptide FF (NPFF), a morphine modulatory peptide, has been identified within discrete autonomic regions in the brainstem and hypothalamus. Triple fluorescence labelling was employed to identify collateral branching projections of NPFF neurons located within the nucleus tractus solitarius (NTS) and in the region of the hypothalamus between the dorsomedial and ventromedial hypothalamus. Injections of two retrograde tracers, rhodamine- and fluorescein-labelled latex microspheres into the pontine parabrachial nucleus (PBN) and the ventrolateral medulla resulted in labelling of NPFF neurons in the NTS that contained one (double-labelled) or both (triple-labelled) tracers. Within the NTS, most double- and triple-labelled NPFF neurons were localized at the level of the area postrema or just rostral to it and within the medial and dorsomedial subdivisions of the nucleus. Injections of tracers into the PBN and hypothalamic paraventricular nucleus revealed double- and triple-labelled NPFF neurons, a majority of which were located in a zone between the dorsomedial and ventromedial hypothalamus. These results indicate that NPFF neurons in the brainstem and hypothalamus may simultaneously transmit signals to their target nuclei in the brainstem and forebrain. This coordinated signalling may lead to synchronized responses of NPFF target sites and provide insights into the role of this peptide in cardiovascular and nociceptive responses.

Animals↗

Distribution of calretinin, calbindin-D28k and parvalbumin in the hypothalamus of the squirrel monkey.

The immunohistochemical approach was used to study the distribution of three calcium-binding proteins of the 'EF hand' family, namely calretinin, calbindin-D28k and parvalbumin, in the preoptico-hypothalamic complex of the squirrel monkey (Saimiri sciureus). These three calcium-binding proteins were found to be heterogeneously distributed in the primate hypothalamus. Neurons expressing high levels of calretinin immunoreactivity were particularly abundant in the infundibular (arcuate) nucleus, the suprachiasmatic nucleus, the lateral area and the dorsomedial nucleus of the hypothalamus. Neurons displaying immunoreactivity for calbindin-D28k were especially numerous in the medial preoptic area and diagonal band nucleus, as well as in the magnocellular subdivision of the paraventricular nucleus, the suprachiasmatic nucleus, the supraoptic nucleus, the infundibular nucleus, the ventromedial nucleus and the mammillary bodies of the hypothalamus. Fibers displaying intense immunoreactivity for either calretinin or calbindin-D28k were very abundant in the median eminence of the hypothalamus. In contrast to calretinin- and calbindin-D28k, parvalbumin was largely absent from the primate preoptico-hypothalamic complex. Parvalbumin-immunoreactive neurons occurred in significant number only in the most lateral portion of the medial mammillary nucleus in the squirrel monkey. The results of the present study suggest that calretinin and calbindin-D28k may act, either in concert or in a complementary manner, so as to participate in some specific aspects of the multifarious role of the hypothalamus in primates. In contrast to the other two calcium-binding proteins, parvalbumin is unlikely to be involved in a significant manner in hypothalamic functions in primates.

Animals↗

Lithium-induced inositol depletion in rat brain after chronic treatment is restricted to the hypothalamus.

The influence of acute and chronic lithium administration on inositol content was examined in five different regions of the rat brain: caudate, cerebellum, cortex, hippocampus and hypothalamus. After acute administration of lithium at doses of 3, 6 or 10 mEq kg-1, no significant reductions of inositol were found in any brain region. Also no significant changes were observed in cortex, caudate, hippocampus and cerebellum after chronic treatment with lithium-containing diet, which led to brain concentrations of lithium in the therapeutic range. However, a moderate but significant reduction of inositol was under these conditions observed in the hypothalamus. At basal conditions, ie in control rats not treated with lithium, the inositol content in various brain areas was different, the hypothalamus containing the highest inositol concentration (4.4 mmol kg-1 wet weight) and the cortex the lowest (2.3 mmol kg-1 wet weight). It is concluded that chronic lithium treatment at therapeutically relevant brain concentrations does not evoke major changes in the inositol content of the brain but induces a moderate decrease which is restricted to the hypothalamus. The results are discussed with respect to the potential function of the hypothalamus in affective disorders.

Animals↗

Cyclic AMP generation in hypothalamus of hypertension-prone and -resistant rats.

1. This noradrenaline-induced accumulation of cyclic AMP is decreased in both the anterior and the posterior hypothalamus of hypertension-prone as compared with resistant rats, but is similar in the cortex. 2. The noradrenaline-induced accumulation of cyclic AMP is decreased in the posterior hypothalamus as compared with the anterior hypothalamus of both strains. 3. The decreased sensitivity to phosphodiesterase inhibitor in the hypothalamus of hypertension-prone as compared with resistant rats suggests that strain differences in phosphodiesterase activity may exist. 4. Since differences in cyclic AMP were found in the hypothalamus and the medulla oblongata, regions involved in blood pressure control, but not in the cortex, they may be relevant to the diverse susceptibility to hypertension of hypertension-prone and resistant rats.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗