Changes In Noradrenaline Turnover Research Articles

Differential Sympathetic Activation of Adipose Tissues by Brain-Derived Neurotrophic Factor.

Centrally administered brain-derived neurotrophic factor (BDNF) decreases body adiposity beyond what can be accounted for by decreased food intake, implying enhanced lipid metabolism by BDNF. Consistent with this notion, intracerebroventricular (icv) injection of BDNF in rats increased the expression of lipolytic enzymes in white adipose tissues (WAT) and increased circulating concentrations of lipolytic products without changing the levels of adrenal gland hormones. This suggests that central BDNF-induced lipid mobilization is likely due to sympathetic neural activation, rather than activation of the adrenocortical or adrenomedullary system. We hypothesized that BDNF activated sympathetic innervation of adipose tissues to regulate lipolysis. Rats with unilateral denervation of interscapular brown adipose tissue (BAT) and different WAT depots received icv injections of saline or BDNF. Both intact and denervated adipose tissues were exposed to the same circulating factors, but denervated adipose tissues did not receive neural signals. Norepinephrine (NE) turnover (NETO) of BAT and WAT was assessed as a measure of sympathetic activity. Findings revealed that central BDNF treatment induced a change in NETO in some but not all the adipose tissues tested. Specifically, greater NETO rates were found in BAT and gonadal epididymal WAT (EWAT), but not in inguinal WAT (IWAT) or retroperitoneal WAT (RWAT), of BDNF-treated rats compared to saline-treated rats. Furthermore, intact innervation was necessary for BDNF-induced NETO in BAT and EWAT. In addition, BDNF increased the expression of lipolytic enzymes in both intact and denervated EWAT and IWAT, suggesting that BDNF-induced WAT lipolysis was independent of intact innervation. To summarize, centrally administered BDNF selectively provoked sympathetic drives to BAT and EWAT that was dependent on intact innervation, while BDNF also increased lipolysis in a manner independent of intact innervation.

Organ-specific changes in norepinephrine turnover against various stress conditions in thermoneutral mice.

The effects of three stressors of different categories, namely cold exposure, immobilization, and lipopolysaccharide (LPS) treatment, on sympathetic nerve activity were examined by assessing its biochemical index norepinephrine (NE) turnover in peripheral organs of C57BL/6 mice. NE turnover was assessed by measuring the decrease in the organ NE concentration 3 h after inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine. NE turnover in brown adipose tissue (BAT) in the room temperature (23 degrees C) control group was as high as that in the cold exposure (4 degrees C) group. Similarly, the mRNA level of the thermogenic marker uncoupling protein 1 (UCP1) in the room temperature control group was as high as that in the cold exposure group. As sympathetic stimulation upregulates the UCP1 mRNA level, we thought that sympathetic nerve tonus in BAT was already accelerated at room temperature. To exclude factors affecting basal sympathetic nerve activity, mice housed at thermoneutral temperature (30 degrees C) were used as controls for the subsequent experiments. In this condition, cold exposure accelerated NE turnover in the BAT, as well as heart and pancreas. The corticosterone level showed a higher trend in the cold exposure group in comparison to the control group. Immobilization accelerated NE turnover in the spleen, pancreas, and white adipose tissue and elevated the corticosterone level. LPS (3 mg/kg, i.p.) did not affect NE turnover in all peripheral organs but elevated the corticosterone level. In summary, the sympathetic nervous and adrenocortical responses to three stressors differed greatly. In particular, sympathetic responses showed clear organ-specific acceleration patterns. This important feature may improve our understanding of the multiplicity of biological responses.

Maternal sympathetic stress impairs follicular development and puberty of the offspring.

Chronic cold stress applied to adult rats activates ovarian sympathetic innervation and develops polycystic ovary (PCO) phenotype. The PCO syndrome in humans originates during early development and is expressed before or during puberty, which suggests that the condition derived from in utero exposure to neural- or metabolic-derived insults. We studied the effects of maternal sympathetic stress on the ovarian follicular development and on the onset of puberty of female offspring. Timed pregnant rats were exposed to chronic cold stress (4 °C, 3 h/daily from 1000 to 1300 h) during the entire pregnancy. Neonatal rats exposed to sympathetic stress during gestation had a lower number of primary, primordial, and secondary follicles in the ovary and a lower recruitment of primary and secondary follicles derived from the primordial follicular pool. The expression of the FSH receptor and response of the neonatal ovary to FSH were reduced. A decrease in nerve growth factor (NGF) mRNA was found without change in the low-affinity NGF receptor. The FSH-induced development of secondary follicles was decreased. At puberty, estradiol plasma levels decreased without changes in LH plasma levels. Puberty onset (as shown by the vaginal opening) was delayed. Ovarian norepinephrine (NE) was reduced; there was no change in its metabolite, 3-methoxy-4-hydroxyphenylglycol, in stressed rats and no change in NE turnover. The changes in ovarian NE in prepubertal rats stressed during gestation could represent a lower development of sympathetic nerves as a compensatory response to the chronically increased NE levels during gestation and hence participate in delaying reproductive performance in the rat.

Sympathetic Denervation of One White Fat Depot Changes Norepinephrine Content and Turnover in Intact White and Brown Fat Depots

It is well established that the sympathetic nervous system regulates adipocyte metabolism and recently it has been reported that sensory afferents from white fat overlap anatomically with sympathetic efferents to white fat. The studies described here characterize the response of intact fat pads to selective sympathectomy (local 6-hydroxydopamine injections) of inguinal (ING) or epididymal (EPI) fat in male NIH Swiss mice and provide in vivo evidence for communication between individual white and brown fat depots. The contralateral ING pad, both EPI pads, perirenal and mesenteric pads were significantly enlarged four weeks after denervating one ING pad, but only intrascapular brown fat (IBAT) increased when both ING pads were denervated. Denervation of one or both EPI pad had no effect on fat depot weights. In an additional experiment, NE turnover was inhibited in ING, retroperitoneal, mesenteric and IBAT two days after denervation of both EPI or of both ING pads. NE content was reduced to 10-30% of control values in all fat depots. There was no relation between early changes in NE turnover and fat pad weight 4 weeks after denervation, even though the reduction in NE content of intact fat pads was maintained. These data demonstrate that there is communication among individual fat pads, presumably through central integration of activity of sensory afferent and sympathetic efferent fibers,that changes sympathetic drive to white adipose tissue in a unified manner. In specific situations, removal of sympathetic efferents to one pad induces a compensatory enlargement of other intact depots.

Desipramine prevents the sustained increase in corticotropin‐releasing hormone‐like immunoreactivity induced by repeated immobilization stress in the rat central extended amygdala

Clinical and experimental studies have shown that the activation of corticotropin-releasing hormone (CRH) and noradrenergic systems mediate stress-induced anxiety. Repeated immobilization stress (RIS) has been shown to induce long-lasting anxiety behavior and changes in noradrenaline turnover. The present work was aimed at studying the effect of RIS on the in situ expression of CRH-LI in the central extended amygdala and paraventricular nucleus of the hypothalamus (PVN). Our results showed that RIS for 15 days induces a significant increase of CRH-LI expression in the central extended amygdala. The increase in CRH-LI expression in the central extended amygdala was sustained even after a 25-day stress-free period. The concomitant administration of desipramine (DMI), a specific noradrenaline uptake inhibitor, fully prevented the RIS-induced increase in CRH expression. RIS also induced an increase of CRH-LI expression in the PVN that was prevented by the concomitant DMI administration. In contrast to the sustained effect observed in the central extended amygdala, the RIS-induced increase of CRH-LI expression in the PVN was nonlasting. DMI administration also prevented the RIS-induced increase of adrenal gland weight. The present findings showing that RIS induces a sustained increase of CRH expression in the central extended amygdala suggest that the repeated activation of CRH neurons and CRH receptors in the central extended amygdala may underlie the long-lasting anxiety behavior induced by RIS. Further studies should address the mechanisms involved in the effect of DMI and its eventual relevance in the therapeutic actions of DMI.

Norepinephrine turnover in brown and white adipose tissue after partial lipectomy

Total body fat is restored after the surgical removal (i.e., partial lipectomy) of white adipose tissue (WAT), and this is accomplished via increases in the mass of nonexcised WAT pads. The underlying mechanism for this apparent regulation of total body fat is unknown. One possibility is via the sympathetic nervous system (SNS) innervation of WAT and brown adipose tissue (BAT) through the regulation of lipolysis and thermogenesis, respectively. Specifically, decreases in SNS activity might fuel lipectomy-induced body fat compensation through energy saved from decreased BAT thermogenesis and would promote lipid accretion through decreased WAT basal lipolysis. Therefore, we tested whether lipectomy triggered decreases in the SNS drive [as indicated by the norepinephrine turnover (NETO)] to nonexcised WAT or to BAT, at times before the lipectomy-induced fat pad mass compensation was complete. Siberian hamsters received either sham or bilateral epididymal WAT lipectomy, and NETO was measured in the remaining WAT and interscapular BAT (IBAT) before, and 3 and 6 weeks after surgery. Total dissected WAT, and inguinal and retroperitoneal WAT masses were significantly increased following lipectomy, whereas dorsal subcutaneous WAT and IBAT masses, as well as food intake, were unchanged. The only significant change in NETO was a marked decrease (approximately 90%) in IBAT NETO at Week 3 postlipectomy compared with the sham-lipectomized controls. These findings suggest that the lipid accretion of nonexcised WAT pads triggered by lipectomy may be partially fueled by decreased BAT thermogenesis, inasmuch as decreased IBAT NETO reflects decreased BAT heat production.

Quantitative analysis of corticotropin-releasing factor and arginine vasopressin mRNA in the hypothalamus during chronic morphine treatment in rats: an in situ hybridization study.

The content of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in the hypothalamic paraventricular nucleus (PVN) increases during chronic morphine treatment. Because these experiments cannot distinguish between increased synthesis or reduced release, the present study measured changes in CRF and AVP mRNAs in the PVN by in situ hybridization. Concomitantly, changes in noradrenaline turnover in the PVN and changes in plasma corticosterone release were determined. Male rats were implanted with placebo (naive) or morphine pellets for 7 days. On day 7, groups of rats received an acute injection of either saline i.p. or morphine (30 mg/kg, i.p.). Acute morphine injection did not change the total size of the labelled area for CRF mRNA in the PVN of naive or morphine-pelleted rats, indicating that the number of CRF-containing neurones was unchanged. On the other hand, in rats chronically treated with morphine, the intensity of labelling for CRF mRNA was significantly reduced, suggesting a decrease in the synthesis of CRF. In placebo rats, injection of saline or morphine did not affect the surface hybridized for AVP mRNA. By contrast, in the morphine-group injected with saline, there was a significant reduction in the number of labelled neurones, measured by the size of labelled area. Similarly, there was a decrease in intensity of AVP mRNA expression in the parvocellular and magnocellular neurones of the PVN in the morphine-group injected with saline, suggesting a decreased synthesis of AVP in these neurones. In parallel with the decrease in the expression of CRF and AVP mRNAs in the PVN, there was a pronounced decrease in noradrenaline turnover and in the release of corticosterone in the morphine-pelleted rats. In conclusion, present results show that, in addition to modifications in corticosterone secretion and in noradrenaline turnover, chronic morphine administration produces a reduction in the synthesis of CRF and AVP.

Prenatal stress and glucocorticoid effects on the developing gender-related brainProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Hormonal and neurotransmitter environment of nondifferentiated cells in the developing brain determines many of gender-specific behavioural and neuroendocrine functions. Early postnatal and long-term effects of maternal stress or prenatal glucocorticoid on sex-related peculiarities of the brain morphology, biogenic monoamine turnover, testosterone metabolism, hypothalamic noradrenaline (NA) and adrenocortical responses to an acute stress were studied in Wistar rat offsprings. Maternal stress (1 h immobilization daily for gestational days 15–21) prevented development of sexual dimorphism in neuronal cell nuclei volumes in suprachiazmatic nucleus (SCN) in 10 day old pups. That was associated with a disappearance of male–female differences in NA and 5-hydroxytryptamine turnover in the preoptic area (POA) and dopamine (DA) turnover in the mediobasal hypothalamus (MBH) by decreasing them in male pups. Hydrocortisone acetate (5 mg daily during the last week of pregnancy) produced changes in NA turnover in the POA of males and females which were quite similar to those after maternal stress. Changes in aromatase and 5 α-reductase activities in the POA of male pups were quite opposite as affected by maternal stress or prenatal glucocorticoid. Sexual differences in 5 α-reductase activity in the MBH appeared due to its increase in prenatally stressed male pups. In contrast to adult males, in adult females maternal stress did not restrict hypothalamic NA and blood plasma corticosterone response to acute stress (1 h immobilization). Our findings on morphology and functions of gender-related developing brain areas stand in correlation with modifying effects of maternal stress and prenatal glucocorticoid on behavior and neuroendocrine regulations.

Widespread and lateralized effects of acute traumatic brain injury on norepinephrine turnover in the rat brain

Norepinephrine (NE) has been implicated in recovery of function following traumatic brain injury (TBI). While bilateral decreases in brain NE turnover occur at 6–24 h after TBI, it is unknown what effects unilateral TBI might have on brain NE turnover over the first few minutes after injury. Here male Sprague-Dawley rats had unilateral contusions of either the right or left somatosensory cortex produced by an air driven piston. At 30min after TBI, brain NE turnover was assessed by measuring the ratio of 3-methoxy-4-hydroxyphenylglycol (MHPG) to NE levels in various brain regions. Both right and left TBI produced 32–103% increases in NE turnover at the injury site and in the ipsilateral cerebral cortex surrounding, rostral and caudal to the injury as compared to the contralateral, uninjured site or to the homologous sites in uninjured controls. NE turnover was also altered selectively in some brain areas not affected by right TBI. Left TBI decreased NE turnover by 29% in the frontal cortex contralateral to the injury and by 24% bilaterally in the hypothalamus while increasing locus coeruleus NE turnover by 72% compared to uninjured controls. Thus, unilateral cortical TBI produced predominantly ipsilateral increases in cortical NE turnover but variable, bilateral changes in NE turnover in subcortical areas which were dependent upon the side of injury. These subcortical differences may explain some of the lateralized effects of cortical injury on post-injury behavior.

Prenatal exposure to diazepam causes sex-dependent changes of the sympathetic control of rat spleen

Prenatal exposure to low doses of benzodiazepines has been found to affect immune functions (25,26). Because the immune system is controlled by the autonomic nervous system, we investigated the sympathetic activity in the spleen for a possible contribution to impaired immune function. Twenty-eight-day-old offspring of prenatally diazepam- or vehicle-treated Long-Evans rats (diazepam 1.25 mg/kg/day SC, gestational day 14–20) were injected IP with sheep red blood cells (SRBC) to evoke an immune reaction. Baseline splenic noradrenaline (NA) turnover was higher in females than in males. Prenatal diazepam treatment resulted in reduced NA turnover in the spleen of SRBC-stimulated female, but not male, offspring. β-Adrenergic binding sites in spleen membrane fractions, studied with 3H-dihydroalprenolol, showed no differences, indicating that changes in NA turnover were not compensated by changes in receptor expression. Sex-specific developmental effects of diazepam have been described earlier, e.g., in selective effects on perinatal corticosterone levels in female offspring (26).

Increased cardiac production of dihydroxyphenylalanine (DOPA) during sympathetic stimulation in anaesthetized dogs

Entry of dihydroxyphenylalanine (DOPA) into plasma from specific organs may reflect regional activity of tyrosine hydroxylase, the enzyme responsible for the immediate synthesis of DOPA and rate-limiting for subsequent formation of catecholamines. Therefore, cardiac spillovers of DOPA, noradrenaline and the intraneuronal metabolite of noradrenaline, dihydroxyphenylglycol (DHPG), were examined during two periods of graded electrical stimulation of the sympathetic nerves to the heart in anaesthetized dogs. Responses were examined before and after neuronal uptake blockade with desipramine. Cardiac spillover of DOPA increased by 1.8- and 4.4-fold during sympathetic stimulation before desipramine and by 1.6- and 3.3-fold after desipramine. Fold increases in cardiac spillover of DOPA were much lower than but positively related with fold increases in noradrenaline spillover (5.9- and 13.8-fold increases before and 9.0- and 15.8-fold increases after desipramine). Increases in cardiac spillover of DHPG (1.5- and 2.3-fold increases) were blocked by desipramine so that fold changes in spillover of DOPA were greater than and poorly related to changes in spillover of DHPG. Fold increases in cardiac spillover of DOPA showed a close one-to-one positive relationship with fold increases in the sum of cardiac spillovers of noradrenaline and dihydroxyphenylglycol before and after desipramine. For a given fold increase in noradrenaline release, transmitter turnover is increased fractionally and noradrenaline synthesis need also only increase fractionally to maintain transmitter stores constant. The close relationship between fold increases in cardiac spillover of DOPA and combined spillovers of noradrenaline and DHPG is consistent with regulation of tyrosine hydroxylase activity to match changes in noradrenaline synthesis with changes in noradrenaline turnover. Changes in cardiac spillover of DOPA appear to reflect local changes in tyrosine hydroxylase activity.

Interleukin-1 increases norepinephrine turnover in the spleen and lung in rats

To clarify effects of interleukin-1 on sympathetic nerve activity, norepinephrine turnover in various organs was assessed in rats after intraperitoneal injection of recombinant human interleukin-1 beta. Interleukin-1 administration increased norepinephrine turnover in the spleen, lung and hypothalamus without appreciable effect in the heart, liver, submandibular gland, thymus, pancreas, brown adipose tissue and medulla oblongata. Similar changes in norepinephrine turnover were also found after the administration of bacterial endotoxin. It was concluded that interleukin-1 activates the sympathetic nerves specifically in the spleen and lung.

Sympathetic response to exercise in various tissues with advancing age.

It was the purpose of this investigation to examine any age-related changes in norepinephrine turnover (NEt) in four tissues at rest and during exercise. Fischer 344 rats 6 (n = 20) and 25 mo of age (n = 20) were received from the National Institute on Aging. NEt was determined at rest, during 30 min of submaximal exercise, and at maximal exercise by administration of alpha-methyl-p-tyrosine, a competitive inhibitor of tyrosine hydroxylase. Resting NE declined with age in both heart (38.2 vs. 30.5 ng.g-1.h-1) and liver (11.2 vs. 6.4 ng.g-1.h-1). NEt was greater in the older animals compared with the young animals in heart (120.9 vs. 169.5 ng.g-1.h-1), liver (23.1 vs. 38.9 ng.g-1.h-1), and adrenals (74.0 vs. 98.4 ng.mg-1.h-1) during submaximal exercise. In response to maximal exercise, NEt varied depending on age and tissue. It was concluded that, in response to exercise stress, the older animals generally demonstrated a higher NEt (reflecting elevated sympathetic activity) perhaps because of a decreased adrenergic receptor sensitivity and/or responsiveness.

Effects of acute morphine administration on noradrenaline turnover and metabolism in various brain parts of control and handled rats.

The main purpose of these experiments was to study whether the morphine-induced changes in cerebral noradrenaline (NA) turnover differ between various brain areas of male Wistar rats assessed by the alpha-methyl-p-tyrosine (alpha MT)-induced NA depletion. The effects of repeated saline injections (20 days) on the morphine-induced changes in NA and also in free and sulphated 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG) concentrations were studied. 5 to 40 mg/kg of morphine reduced the alpha MT-induced NA depletion in the cortical hemispheres, while 40 mg/kg of morphine enhanced it in the lower brain stem. 10 mg/kg of morphine lowered the NA concentration in limbic forebrain and hypothalamus and increased it in the cortical areas. It also elevated the MOPEG concentrations in all brain parts with the sole exception of sulphated MOPEG in the cortical hemispheres. Naltrexone antagonized the morphine-induced changes in NA turnover and MOPEG concentrations. The only significant handling-induced change was the elevation of NA concentrations in the hypothalamus. The increasing effect of morphine on the sulphated MOPEG concentration in the prefrontal cortex and the lower brain stem was attenuated in handled rats. In conclusion, these findings show that, the response of cortical NA neurones to acute morphine administration is retardation of turnover rather than activation which occurs most notably in the lower brain stem. Furthermore, the responses are modified by previous exposure of rats to handling.

Adrenergic mechanisms during hypertension induced by sucrose and/or salt in the spontaneously hypertensive rat.

Spontaneously hypertensive rats received tap water, 1% NaCl, 5% sucrose or NaCl and sucrose in combination for 4 weeks. The blood pressure (tail plethysmography) and renal excretions of sodium and catecholamines were followed. After 4 weeks the noradrenaline turnover (disappearance after alpha-methyltyrosine) was assessed in the heart and brain. In pithed rats the pressor responses to intravenous noradrenaline and to electrical stimulation of the spinal sympathetic nerves (SNS) were determined together with the rise in plasma noradrenaline concentrations during the SNS. Salt alone caused an increase in peripheral sympathetic activity, measured as turnover of noradrenaline in the heart and spillover of noradrenaline in the urine, a modest enhancement of vascular responsiveness to noradrenaline and a blood pressure elevation. Sucrose alone increased the peripheral sympathetic activity but influenced neither the vascular responsiveness to noradrenaline nor the basal blood pressure. The largest increase in sympathetic activity and in blood pressure was observed with sucrose and salt in combination. The release of noradrenaline from the sympathetic nerve endings was not significantly influenced by any diet regime. The changes in noradrenaline turnover in the heart was accompanied by reciprocal changes in brain stem noradrenaline turnover.

Effects of insulin on rat brain noradrenaline

A single intracardial injection of streptozotocin produced a significant increase in rat hypothalamic noradrenaline while no changes were observed in the olfactory tubercles. The parenteral administration of a single dose of insulin decreased rat hypothalamic noradrenaline; the effect had a rapid onset and lasted for at least six hours. Similar noradrenaline reductions were observed in the olfactory tubercles but in this tissue the depletion started later and recovered earlier. In addition, in olfactory tubercles after insulin injection, tyrosine level and dopamine metabolism were increased. The results show that the increases in hypothalamic NA observed in streptozotocin diabetic rats are counteracted by insulin administration and possibly the consequence of changes in noradrenaline turnover.

Effect of short-term administration of vasopressin on arterial pressure and norepinephrine turnover in Long-Evans rats.

Vasopressin (AVP) in acute experiments has been shown to influence cardiovascular reflexes, but the effect of a more prolonged administration of AVP on the sympathetic nervous system has not been investigated. Long-Evans rats were treated for 7 days with AVP (Pitressin tannate in oil, with single daily doses of 100 or 500 mU.100 g-1, s.c.) to determine whether AVP alters norepinephrine (NE) turnover in kidney, intestine, or skeletal muscle. Control rats were given equal doses of peanut oil daily. NE turnover was determined by measuring the decline in tissue levels of NE for 8 h after inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (300 mg.kg-1, i.p. every 4 h). Measurements of water intake, urine output, and urine osmolality showed that chronic administration of the high dose, but not the low dose, of AVP produced maintained increases in urine osmolality and decreases in water intake and urine output. Body weight, plasma osmolality, plasma electrolytes, and hematocrit were not significantly altered by AVP treatment, but mean arterial pressure was elevated significantly (control, 105 +/- 3 mmHg versus AVP, 119 +/- 4 mmHg, p less than 0.05) (1 mmHg = 133.3 Pa) in the high dose group. Plasma renin activity was decreased slightly, but significantly in rats treated with the high dose of AVP. Compared with results in control animals, there were no statistically significant changes in NE turnover after chronic administration of either the low or the high dose of AVP. The results indicate that administration of AVP for 7 days to rats in normal fluid balance does not result in a decrease in NE turnover in peripheral organs.

P-334 - Changes in noradrenaline turnover in the rat brain regions induced by yohimbine, a blocker of alpha-2 adrenoceptor, and immobilization stress

P-334 - Changes in noradrenaline turnover in the rat brain regions induced by yohimbine, a blocker of alpha-2 adrenoceptor, and immobilization stress

Differential changes in noradrenaline turnover in specific regions of rat brain produced by controllable and uncontrollable shocks.

A series of three studies was performed to investigate the effects of the ability to avoid or escape shock (controllability) and the lack of ability to do so (uncontrollability) on noradrenergic neurons in various brain regions of male Wistar rats. The levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in the hypothalamus, amygdala, thalamus, midbrain, hippocampus, cerebral cortex, pons plus medulla oblongata, and basal ganglia were measured fluorometrically. These studies indicated that after 3 hr and 6 hr in a free operant avoidance-escape stress procedure, the experimental rats able to avoid or escape shock showed greater increases in NA turnover (lower NA levels and higher MHPG-SO4 levels) in specific brain regions (i.e., the hypothalamus, amygdala, and thalamus) than the yoked rats unable to control the same shock. After 21 hr of stress, in contrast to stress of either 3-hr or 6-hr duration, the yoked rats exhibited a more marked enhancement of NA turnover in these brain regions than did experimental rats. Once shock-controlling responses had been acquired and well established by experimental rats, the responses of NA neurons in these rats did not differ markedly from those in the nonshocked control rats. Yoked rats given the same repetitive sessions of uncontrollable shock displayed sustained increases in NA turnover preferentially in the hypothalamus and amygdala, compared with the experimental rats. These results suggest that NA release in specific brain regions in the experimental "coping" rats is increased before the rats have learned the effective coping response. However, once a coping response is firmly established, NA release is reduced.

Differential changes in noradrenaline turnover in specific regions of rat brain produced by controllable and uncontrollable shocks.

Differential changes in noradrenaline turnover in specific regions of rat brain produced by controllable and uncontrollable shocks.