Hypothalamic Norepinephrine Levels Research Articles

Effects of central RVD-hemopressin(α) administration on anxiety, feeding behavior and hypothalamic neuromodulators in the rat.

The endocannabinoid (eCB) system is strongly involved in the regulation of anxiety and feeding behavior. RVD-hemopressin(α) [RVD-hp(α)], a N-terminally extended form of hemopressin, is a negative allosteric modulator of the cannabinoid (CB) 1 receptor and a positive allosteric modulator of CB2 receptor which has been recently reported to exert anxiolytic/antidepressant and anorexigenic effects after peripheral administration in rats. Pharmacological evidences reported a possible link between brain hypocretin/orexin, monoamine and eCB systems, as regards appetite and emotional behavior control. Considering this, the aim of our work was to investigated the effects of RVD-hp(α) on anxiety like behavior and food intake after central administration and related it to monoamine levels and orexin-A gene expression, in the hypothalamus. We have studied the effects of central RVD-hp(α) (10nmol) injection on anxiety-like behavior and feeding using different behavioral tests. Hypothalamic levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and gene expression of orexin-A and proopiomelanocortin (POMC) were measured by high performance liquid chromatography (HPLC) and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis, respectively. Central RVD-hp(α) administration decreased locomotion activity and stereotypies. Moreover, RVD-hp(α) treatment inhibited anxiogenic-like behavior and food intake, NE levels and orexin-A gene expression, in the hypothalamus. Concluding, in the present study we demonstrated that central RVD-hp(α) induced anxiolytic and anorexigenic effects possibly related to reduced NE and orexin-A and POMC signaling, in the hypothalamus. These findings further support the central role of the peptide in rat brain thus representing an innovative pharmacological approach for designing new anorexigenic drugs targeting eCB system.

Selection for catatonia: Effect on sexual function and estrous cycle synchronization

Body, ovary, and uterus weights; estrous cycle; dopamine and norepinephrine levels in the hypothalamus; and testosterone levels in blood plasma have been recorded in 2- to 3-month-old GC female rats selected for elevated catatonia response and compared with the outbred Wistar stock. The body weights of GC rats are lower, and the cyclic linkage between the ovaries and the uterus is disrupted, as is apparent from a reduced diestrus ovary weight and a lower estrogen-dependent uterus weight increase in comparison to those of Wistar. A statistically significant synchronization of estrous cycles is observed in GC rats kept in standard cages, five to seven animals per cage. It includes a larger number of matches of individual estrus phases so as to form a group estrus phase of their 4- to 5-day-long estrous cycle. Synchronized estrus phases occur in 50–60% of GC rats, which is significantly more than in Wistar rats (30–40%). With reduced dopamine and norepinephrine levels in hypothalami of GC rats, the levels of these monoamines are higher in estrus and low in diestrus. Testosterone levels in diestrus GC females are higher than in estrous or Wistar ones.

Social-cooperation differs from individual behavior in hypothalamic and striatal monoamine function: Evidence from a laboratory rat model

Explanations and models of cooperation usually focus on the economics of an individual's invested effort and outcomes while down-playing social dimensions of naturally occurring cooperation. This study examined whether cooperative and individual behaviors differ in monoaminergic function in a manner that may explain the reported ‘bias for cooperation’ even under conditions where no immediate economic gains exist. Cooperation, represented by pairs of rats reinforced for coordinated shuttles within a shared chamber (COOP), was compared with rats shuttling for reinforcements individually (IND), and behaviorally naïve rats (NAïVE). Following training, the hypothalamus and striata were sampled and the activity patterns of the noradrenergic, serotonergic and dopaminergic systems were assessed using HPLC analyses. By matching the proportions of reinforced individual shuttles for COOP and IND rats the economic differences of invested effort (shuttles) and outcomes (obtained reinforcements) were neutralized. Nevertheless, differences were evident in monoaminergic functions. In comparison with IND rats, COOP rats showed significantly higher hypothalamic norepinephrine levels and exhibited a trend toward higher striatal serotonin levels. Differences in levels of dopaminergic metabolites were restricted to the right striatum; compared to IND rats, COOP rats exhibited significantly higher levels of HVA, whereas NAÏVE rats exhibited significantly higher DOPAC levels.Since economic differences between cooperative and individual shuttling were neutralized, the results demonstrate a relationship between social cooperation and a distinct activity pattern in brain mechanisms that were related with arousal, goal directed behaviors and motivation and further highlight the key role of social behaviors in the reported ‘bias for cooperation’.

The neuroimmune changes induced by cohabitation with an Ehrlich tumor-bearing cage mate rely on olfactory information

Cohabitation for 14 days with Ehrlich tumor-bearing mice was shown to increase locomotor activity, to decrease hypothalamic noradrenaline (NA) levels, to increase NA turnover and to decrease innate immune responses and decrease the animals' resistance to tumor growth. Cage mates of a B16F10 melanoma-bearer mice were also reported to show neuroimmune changes. Chemosignals released by Ehrlich tumor-bearing mice have been reported to be relevant for the neutrophil activity changes induced by cohabitation. The present experiment was designed to further analyze the effects of odor cues on neuroimmune changes induced by cohabitation with a sick cage mate. Specifically, the relevance of chemosignals released by an Ehrlich tumor-bearing mouse was assessed on the following: behavior (open-field and plus maze); hypothalamic NA levels and turnover; adrenaline (A) and NA plasmatic levels; and host resistance induced by tumor growth. To comply with such objectives, devices specifically constructed to analyze the influence of chemosignals released from tumor-bearing mice were employed. The results show that deprivation of odor cues released by Ehrlich tumor-bearing mice reversed the behavioral, neurochemical and immune changes induced by cohabitation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. Our results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion.

Odor cues from tumor-bearing mice induces neuroimmune changes

Cohabitation for 14 days with an Ehrlich tumor-bearing mice was shown, among others, to increase locomotor activity, and hypothalamic noradrenaline levels and turnover, to decrease the innate immune responses and animal resistance to tumor growth. The present experiment was designed to access the relevance of tactile, olfactory, and visual communication to the neuroimmune changes induced by cohabitation with a tumor-bearing partner. Mice that were not allowed to perceive odor cues from their sick partners presented no alterations in neutrophil activity, a fact not observed after visual deprivation and physical isolation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. The present results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion.

High fructose diet increases anterior hypothalamic alpha 2-adrenoceptors responsiveness

Activation of alpha(2)-adrenoceptors in the anterior hypothalamic area (AHA) decreases sympathetic nervous system activity and blood pressure. The aim of the present study was to evaluate activity of pre- and postsynaptic alpha(2)-adrenoceptors in the AHA of fructose hypertensive rats (F), an animal model of insulin resistance and hypertension. The AHA of Control (C) and F anaesthetized rats was perfused with Ringer solution in the absence or presence of clonidine (100 or 300 microg ml(-1)) using reverse microdialysis. Clonidine effects on mean arterial pressure (MAP) and heart rate (HR), and on hypothalamic noradrenaline levels were measured along perfusion time. Noradrenaline extracellular levels in the AHA were significantly diminished in F hypertensive rats compared to C animals. The depressor effect of intrahypothalamic perfusion of clonidine on MAP was enhanced in F rats compared with C animals. Intrahypothalamic perfusion of clonidine reduced HR only in F rats. The effect of clonidine on noradrenaline hypothalamic extracellular levels was enhanced in F rats. These results suggest, in our experimental conditions, the existence of an increased responsiveness of pre- and postsynaptic alpha(2)-adrenoceptors in the AHA of F hypertensive rats. This fact could be a consequence of a compensatory supersensitivity of alpha-adrenoceptors due to a decrease in noradrenaline release from nerve terminals located in the AHA.

Attenuation of the development of DOCA salt hypertension by a high Mn intake in the rat

The effects of a high Mn intake on blood pressure, vascular reactivity and central catecholamine levels were studied in DOCA salt-hypertensive rats. High Mn intake inhibited blood pressure elevation in DOCA salt rats but did not modify it in normotensive rats. The blood pressure-lowering effect of Mn was associated with inhibited cardiac hypertrophy and increased natriuresis. Pharmacological studies in blood vessels showed that high Mn intake normalized vasoconstriction and sensitivity to norepinephrine of isolated and perfused mesenteric vascular beds from DOCA salt rats. Furthermore, high Mn intake improved the endothelium- and NO-dependent relaxation in isolated aortae from DOCA salt-hypertensive rats but not in those from normotensive rats. Norepinephrine levels were higher in the hypothalamus of DOCA salt-hypertensive rats than in those of normotensive rats, and high Mn intake decreased norepinephrine levels in hypothalamus of DOCA salt rats. In conclusion, a high Mn intake attenuated the development of hypertension with beneficial vascular and central effects. Mechanisms related to the pathophysiological development of DOCA salt hypertension may be involved.

Genetic differences in brain monoamines level in Pietrain and Duroc pigs exposed to acute restraint stress

SummaryThe distribution and endogenous concentrations of norepinephrine (NE), epinephrine (E), dopamine (DA) as well as DA metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5‐hydroxytryptamine (5‐HT) and the main 5‐HT metabolite – 5‐hydroxyindole‐3‐acetic acid (5‐HIAA), were measured by HPLC in 15 brain areas of control and immobilized adult Duroc (D) and Pietrain (P) pigs. The animals were immobilized for 15, 30 and 60 min in the prone position. Control pigs displayed the pattern of regional distribution of brain monoamines similar to that described in other species. Absolute values of NE and E were much higher in the hypothalamus and the preoptic area of pigs than in other species. The concentration of E was seven times higher in the hippocampus posterior in P pigs as compared to D pigs. Also, in most structures DOPAC/DA ratio was relatively high, which points to strains related difference in the turnover of dopamine. In control animals, statistical differences in the bioamine contents were seen between both strains in 25 cases. Epinephrine accounted for more than 12% of the total concentration of both amines in D and 15% in P, this proportion was the highest among the structures compared. The highest concentration of DA and its metabolites – DOPAC and HVA, was revealed in the caudate nucleus and in the nucleus accumbens. Of other structures, the substantia nigra (SN), the septum and the ventral tegmental area (VTA) contained relatively high concentrations of DA, DOPAC and HVA. The 5‐HT level varied from the lowest concentration in the hippocampus posterior, cornu ammonis, nucleus accumbens and the caudate nucleus to the highest concentration in the hypothalamus, the SN, and brain stem areas. This distribution was paralleled by corresponding concentration of 5‐HIAA, being the highest in raphe nuclei (RN). The most conspicuous changes produced by immobilization stress consisted of a substantial decrease in the hypothalamic levels of NE and E in both strains of pig. The level of NE was always higher in D than in P in cornu ammonis, hippocampus posterior, nucleus caudatus, SN, septum, hypothalamus medialis, tectum and olfactory tuberculum. The same was for E in: SN, septum, hypothalamus medialis, and olfactory tubercle. DA, DOPAC and HVA, were changed primarily in SN in P pigs, and in RN in P and D animals. Serotonin (5‐HT) level increased substantially in RN in P pigs. 5‐HIAA level was highly elevated in the RN being always higher in P than in D pigs and in PAG. We suggest that restraint immobilization stress lead to compensatory changes in both brain monoaminergic systems. These changes may affect coping with stress demands mostly in the structures that are proposed to play a major role in the pig responsiveness to acute stress conditions.

Role of specific adrenergic receptors in mediating the adrenocorticotropic hormone response to increased nitric oxide levels.

We investigated the role played by catecholamine-dependent pathways in modulating the ability of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) to release adrenocorticotropic hormone (ACTH) following its intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. We first showed that the nonspecific adrenergic agonist noradrenaline, the alpha- or beta-adrenergic agonists phenylephrine or dobutamine, or the noradrenergic uptake inhibitor desipramine, all significantly stimulated ACTH secretion by freely moving, nonanaesthetized rats. We then observed that destruction of noradrenergic nerve endings with the neurotoxin 6-hydroxydopamine, respectively abolished and significantly decreased the ACTH response to the i.c.v. or i.v. administration of SIN-1. Finally, we sought to identify the type of adrenergic receptor(s) mediating the influence of catecholamines. beta-Adrenergic receptors did not appear to be involved in the stimulatory effect of SIN-1 regardless of its route of injection. By contrast, alpha 2-adrenergic receptors played an important role in the ACTH response to i.v. or i.c.v. administered SIN-1. Collectively, these results indicate that while hypothalamic alpha 1- and beta-adrenergic receptors are important for hypothalamic-pituitary-adrenal (HPA) axis activity, only alpha 2-adrenergic receptors are involved in modulating the ability of NO to release ACTH. Our laboratory and others have previously reported that NO increased hypothalamic noradrenaline levels, while conversely noradrenaline up-regulated levels of NO synthase, the enzyme responsible for NO formation; and that injection of corticotropin-releasing factor into the brain ventricles releases catecholamines and stimulates NO formation. Taken together with these observations, our results point to complex functional relationships between NO, catecholamines and the HPA axis.

Potent serotonin (5-HT) 2A receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome

The serotonin (5-HT) syndrome is the most serious side effect of antidepressants, and it often necessitates pharmacotherapy. In the present study, the efficacy of several drugs was evaluated in an animal model of the 5-HT syndrome. When 2 mg/kg of clorgyline, a type-A monoamine oxidase inhibiting antidepressant, and 100 mg/kg of 5-hydroxy- l-tryptophan, a precursor of 5-HT, were administered intraperitoneally to rats to induce the 5-HT syndrome, the rectal temperature of the rats increased to more than 40°C, and all of the animals died by 90 min after the drug administration. The noradrenaline (NA) levels in the anterior hypothalamus, measured by microdialysis, increased to 15.9 times the preadministration level. Pretreatment with propranolol (10 mg/kg), a 5-HT 1A receptor antagonist as well as a beta-blocker, and dantrolene (20 mg/kg), a peripheral muscle relaxant, did not prevent the death of the animals, even though these two drugs suppressed the increase in rectal temperature to some extent. Chlorpromazine and cyproheptadine prevented the lethality associated with the 5-HT syndrome only at high doses. By contrast, pretreatment with ritanserin (3 mg/kg) and pipamperone (20 mg/kg), both potent 5-HT 2A receptor antagonists, completely prevented the increase in rectal temperature and death of the animals, and the hypothalamic NA levels in these two groups increased less than that in the other groups. These results suggest that potent 5-HT 2A receptor antagonists are the most effective drugs for treatment of the 5-HT syndrome, and that NA hyperactivity occurs in the 5-HT syndrome.

Effects of arsenite on central monoamines and plasmatic levels of adrenocorticotropic hormone (ACTH) in mice

We studied the effects of chronic arsenic exposure on brain monoamines and plasma levels of adrenocorticotropic hormone (ACTH) of mice. After weaning, mice received arsenic (0, 20, 40, 60 or 100 ppm) in drinking water over a period of 9 weeks. Monoamine content was quantified in different brain regions, arsenic was quantified in brain tissue and ACTH levels in plasma. Brain arsenic concentrations up to 200 ng/g showed a significant correlation with exposure levels and produced slight modifications in regional monoamine levels. ACTH plasma levels were significantly associated with norepinephrine (NE) concentrations in the medulla and pons, but not with hypothalamic NE levels. ACTH levels were significantly higher in the group exposed to 20 ppm. Dopamine showed significant dose-related decreases in the hypothalamus. These results show that chronic sodium arsenite exposure produces changes in central monoamines, which are not associated on a dose-dependent basis with major alterations in plasma ACTH.

Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice

The genetically, seasonally, and diet-induced obese, glucose-intolerant states in rodents, including ob/ob mice, have each been associated with elevated hypothalamic levels of norepinephrine (NE). With the use of quantitative autoradiography on brain slices of 6-wk-old obese (ob/ob) and lean mice, the adrenergic receptor populations in several hypothalamic nuclei were examined. The binding of [(125)I]iodocyanopindolol to beta(1)- and beta(2)-adrenergic receptors in ob/ob mice was significantly increased in the paraventricular hypothalamic nucleus (PVN) by 30 and 38%, in the ventromedial hypothalamus (VMH) by 23 and 72%, and in the lateral hypothalamus (LH) by 10 and 15%, respectively, relative to lean controls. The binding of [(125)I]iodo-4-hydroxyphenyl-ethyl-aminomethyl-tetralone to alpha(1)-adrenergic receptors was also significantly increased in the PVN (26%), VMH (67%), and LH (21%) of ob/ob mice. In contrast, the binding of [(125)I]paraiodoclonidine to alpha(2)-adrenergic receptors in ob/ob mice was significantly decreased in the VMH (38%) and the dorsomedial hypothalamus (17%) relative to lean controls. This decrease was evident in the alpha(2A)- but not the alpha(2BC)-receptor subtype. Scatchard analysis confirmed this decreased density of alpha(2)-receptors in ob/ob mice. Together with earlier studies, these changes in hypothalamic adrenergic receptors support a role for increased hypothalamic NE activity in the development of the metabolic syndrome of ob/ob mice.

Alterations of brain monoamine levels in pigs exposed to acute immobilization stress.

Concentrations of noradrenaline (NA), adrenaline (A), dopamine (DA) and 5-hydroxytryptamine (5-HT), as well as DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and the main 5HT metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), were measured using the HPLC technique in 15 brain areas of control and immobilized Duroc pigs. The animals were immobilized for 5, 15, 30 and 60 min in a prone position. Control pigs displayed patterns of regional distribution of brain monoamines similar to those described in other species, especially rats and dogs. However, absolute values of noradrenaline and adrenaline in the hypothalamus were much higher than in other species. Also, in most structures, the DOPAC/DA ratio was relatively high, in comparison to a relatively low HVA/DA ratio, which suggests a species-related difference in the turnover of dopamine. The most conspicuous changes produced by immobilization stress consisted of a substantial decrease in the hypothalamic levels of noradrenaline and adrenaline. Dopamine and 5-HT turnover was affected in the hippocampus (cornu Ammonis), and in the raphe nuclei. These structures are proposed to play a major role in the responsiveness of pigs to acute stress conditions.

Influence of voluntary exercise on hypothalamic norepinephrine.

We combined hypothalamic tissue and plasma determinations of norepinephrine, dihydroxyphenylalanine, and dihydroxyphenylglycol with measurements of abdominal fat in voluntary running rats to examine the relationship among exercise training, hypothalamic and sympathetic nervous function, and body fat stores. The hypothalamic concentrations of norepinephrine, dihydroxyphenylalanine, and dihydroxyphenylglycol were reduced after exercise training (P < 0.01), with the amount of norepinephrine being strongly associated with the plasma norepinephrine (r = 0.58, P < 0.05) and dihydroxyphenylglycol (r = 0.65, P = 0.01) concentrations. Exercise training resulted in a diminution in abdominal fat mass (P < 0.01). A strong relationship existed between fat mass and hypothalamic norepinephrine content (r = 0.83, P < 0.001). The presence of a positive relationship between the arterial and hypothalamic norepinephrine levels provides presumptive evidence of an association between noradrenergic neuronal activity of the hypothalamus and sympathetic nervous function. The observation that abdominal fat mass is linked with norepinephrine in the hypothalamus raises the possibility that alterations in body fat stores provide an afferent signal linking hypothalamic function and the activity of the sympathetic nervous system.

The Effect of Acute, Chronic and Chronic Intermittent Stress on the Central Noradrenergic System

HELLRIEGEL E. T. AND A. P. D'MELLO. The effect of acute, chronic, and chronic intermittent stress on the central noradrenergic system. PHARMACOL BIOCHEM BEHAV 57(1/2) 207–214. 1997.—The objective of this investigation was to examine the immediate and long term effects of acute, chronic and chronic intermittent stress on the central noradrenergic system of rats. Male Sprague–Dawley rats were subjected to one hour of physical immobilization stress either as a single exposure, or as 14 exposures applied either on consecutive days, or randomly over 60 days. Animals were sacrificed immediately, 6 h and 24 h following the last stressor. Levels of norepinephrine (NE) and 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-sulfate) were measured in the hypothalamus, hippocampus, cerebral cortex and locus coeruleus region and β-adrenergic receptor (BAR) density was determined in the cortex. Immediately after acute stress, a significant reduction in hypothalamic NE levels and marked increases in MHPG-sulfate levels in all four brain regions were observed. In contrast, immediately after the last stressor of a chronic or chronic intermittent stress regimen, no change in NE concentration was observed while levels of MHPG-sulfate in the four brain regions showed a smaller increase than that observed after an acute stressor. Acute stress induced changes normalized within 6 h while chronic and chronic intermittently stressed animals had altered NE or MHPG-sulfate levels in certain brain regions for up to 6–24 h. Cortical BAR binding parameters remained unchanged after all stress paradigms.

Developmental and regional changes in brain norepinephrine levels in diabetic C57BL/KsJ mice: effects of estradiol and progesterone

Developmental and diabetes-associated changes in regional brain norepinephrine (NE) concentrations, and the influence of estradiol (E) and progesterone (P) on NE levels, were correlated with changes in blood glucose levels and body weight (obesity) in developing 4–16-week-old C57BL/KsJ ( db / db) mice relative to corresponding age-matched control (+/?) parameters. Regional brain (i.e. amygdala, hypothalamus and medulla) NE levels were determined by high performance liquid chromatography. The ( db / db) mice exhibited overt hyperglycemia and obesity relative to controls between 4 and 16 weeks of age. Hypothalamic NE levels in diabetics were chronically elevated as compared to those of age-matched controls by 8 weeks of age, and remained elevated through 16 weeks of age. Regional amygdaloid and medullary NE concentrations were comparable in (+/?) and ( db / db) groups by 16 weeks. E-treatments normalized ( db / db) hypothalamic NE concentrations to control levels between 8 and 16 weeks of age, but had no effect on amygdaloid or medullary values. In contrast, in 16 week old ( db / db) mice, P-treatments elevated hypothalamic and medullary NE levels compared to controls and expected diabetic levels. These data demonstrate that a marked modification in regional brain NE concentrations occurs in association with the overt expression of the diabetes mutation during development in this species. Observed changes in adrenergic influences in specific CNS loci may be therapeutically modulated by ovarian steroid hormones, especially in the hypothalamic locus which is recognized to possess steroid-concentrating neurons. The observed normalization of regional brain NE concentrations by E-therapy may be causally related to the ovarian steroid-modulation of overt hyperglycemia and diabetes-associated neuronal degeneration in ( db / db) mice.

L-type Ca 2+ channel ligands modulate morphine effects on the hypothalamus-pituitary-adrenocortical axis in rats

The role of the L-type Ca 2+ channel in the acute effects of morphine on the hypothalamo-pituitary-adrenocortical (HPA) system was studied by administration of the Ca 2+ channel agonist, BAY K 8644, and the antagonists, verapamil and nimodipine, to rats. Morphine (30 mg/kg i.p.) induced an increase in corticosterone secretion 30 min after injection, which was correlated with a simultaneous change in hypothalamic noradrenaline (NA) and dopamine DA) contents. Pretreatment with verapamil (10 or 20 mg/kg i.p.) or nimodipine (5 mg/kg i.p.) antagonized the HPA activation induced by morphine, blocking both the decrease in hypothalamic NA levels and the elevation in plasma corticosterone induced by the opioid. BAY K 8644 (2 mg/kg i.p.) potentiated the effects of morphine, decreasing the hypothalamic NA content and increasing the release of corticosterone. The Ca 2+ channel antagonist, nimodipine, given alone induced a slight reduction in hypothalamic NA content but did not modify plasma corticosterone levels. Verapamil given alone did not alter HPA activity. Instead, the Ca 2+ agonist decreased the hypothalamic catecholamine content and increased plasma corticosterone levels. These results indicate that Ca 2+ influx is necessary for the expression of opioid actions on the HPA system, and suggest that the Ca 2+ flux in hypothalamic neurons is functionally linked to activation of opioid receptors.

Behavioral and neurochemical changes in response to acute stressors: Influence of previous chronic exposure to immobilization

The effects of daily (2 h) exposure to immobilization (IMO) for 15 days on the behavioral and neurochemical responses of adult male rats to acute stress caused by 2-h IMO or 2-h tail-shock was studied. The brain areas studied were frontal cortex, hippocampus, hypothalamus, midbrain, and pons plus medulla. Chronic exposure to IMO did not alter noradrenaline (NA), 3-methoxy, 4-hydroxyphenyletileneglycol-SO 4 (MHPG-SO 4), serotonin, or 5-hydroxindoleacetic acid (5-HIAA) concentrations in any brain area as measured approximately 20 h after the last exposure to IMO. Exposure to behavioral tests did not modify neurochemical variables except NA levels in the hypothalamus of nonchronically stressed (control) rats. Both exposure to 2-h IMO or 2-h shock significantly decreased NA levels in hypothalamus and midbrain of nonchronically stressed rats. These decreases in response to the two acute stressors were not observed in chronically stressed rats. However, MHPG-SO 4 levels increased to the same extent in control and chronically stressed rats after exposure to the acute stressors. Likewise, increased 5-HIAA concentrations observed in response to acute stressors were similar in control and chronically stressed rats. The inhibition of activity (areas crossed and rearing) in the holeboard caused by acute IMO was less marked in rats previously exposed to the same stressor than in control rats, but the response to schock was similar. In the forced swim test, acute IMO decreased struglling in control rats but tended to increase it in chronically stressed rats. The response to shock followed the same pattern as that to IMO, although it was slight. These data suggest that: (a) cross-adaptation between stressors might or might not exist, depending upon the behavioral test studied; (b) previous chronic stress did not appear to reduced monoaminergic response to the same or a novel acute stressor as evaluated by the increases in MHPG-SO 4 and 5-HIAA levels; (c) apparently, behavioral adaptation to repeated stress was not related to the changes in noradrenergic or serotonergic activity.

Effects of prenatal morphine on adult sexual behavior and brain catecholamines in rats

Female rats exposed to morphine in utero (5–10 mg/kg twice a day on days 11–18 of gestation) were significantly inhibited in their sexual behavior when compared to saline-exposed controls. In contrast, males exposed prenatally to morphine had shorter post-ejaculatory intromission latencies and, after the first test, exhibited increased mounting and intromitting activity relative to controls. Examination of the brain catecholamine content revealed that morphine in utero may permanently alter adult hypothalamic norepinephrine levels in male and female rats. The morphine-induced alterations in hypothalamic norepinephrine levels were sexually dimorphic. In the hypothalamus of male rats, norepinephrine content was increased 95%, whereas in the hypothalamus of female rats it was decreased 57% relative to controls. These results suggests that prenatal morphine exposure, which differentially affects adult male and female sexual behavior, also alters hypothalamic norepinephrine content in a sexually dimorphic fashion.

The physiological role of the pineal gland as the masterswitch of life, turning on at birth breathing and geared to it the function of the autonomic nervous system. The cause of SIDS examined in this context

The proposition is that the masterswitch of life and death is invested in the physiological role of the pineal gland which by its neurohormonal influence and its neuronal connections in the brain gears hypothalamic noradrenaline levels to which the function of the autonomic nervous system (ANS) and breathing are integrated. Sudden death in an apparently healthy infant can be compared to a well known event, to what happens to a plant if you close the masterswitch which distributes energy. The plant stops to function. It is not yet realized that the human plant also functions only as long as the masterswitch of its biological organization in the brain in charge of energy substrate availability — BOESA — to which breathing, the need of O 2, is also geared, is functioning.