Periodic maternal deprivation and lesion of anterodorsal thalami nuclei induce alteration on hypophyso adrenal system activity in adult rats

The hypothalamic-pituitary-adrenal (HPA) axis is normally regulated by extrahypothalamic limbic structures, among these, the anterodorsal thalami nuclei (ADTN), which exert an inhibitory influence on HPA, in basal and acute stress conditions in rats. In the present work we have investigated whether neonatal maternal deprivation (MD) produces long-term changes in the ADTN regulation of HPA activity. Maternal deprivation, in female rats, for 4.5 hs daily, during the first 3 weeks of life, produced at 3 months old, a significant decrease in plasma ACTH concentration (p<0.001) and an increase in plasma corticosterone (C) (p<0.001), compared to control non-deprived rats (NMD). Also MD showed higher plasma epinephrine (E) and norepinephrine (NE) levels than NMD rats. The increase of NE (66.6% p<0.001) was higher than that observed in E (19%). After 30 days of ADTN lesion, plasma ACTH values were higher than in sham lesioned rats, in both NMD and MD animals. ACTH response was greater in MD rats. Plasma C, in NMD, was higher, whereas in MD lesioned animals, it was significantly lower than in sham lesioned. In MD rats, lesion produced a significant increase in plasma E and NE (p<0.001), and again, NE increase was higher than E increase. The more accentuated increase of NE than E, suggests sympathetic nervous system hyperactivity. In summary, neonatal maternal deprivation induces long-term alterations on HPA axis sensitivity and medullo adrenal secretion; enhanced sympathetic nervous system activity and, therefore affected the ADTN inhibitory influence on ACTH and adrenal glands secretion.     

Effects of maternal deprivation on adrenal and behavioural responses in rats with anterodorsal thalami nuclei lesions

There is evidence that repeated maternal isolation of neonatal rats may influence both emotional behavior and Hypothalamic-Pituitary Adrenal (HPA) activity. On the other hand the Anterodorsal Thalami Nuclei (ADTN) exerts an inhibitory influence on the hypophyso-adrenal system under basal and stressful conditions. In the present work we investigated whether neonatal maternal deprivation produces long term effects on the ADTN regulation of behavioral patterns (open field test) and on HPA axis activity. Specifically, we sought to determine whether adult female rats with ADTN lesions, previously isolated for 4.5 hours daily during the first 3 weeks of life, react in endocrinologically and behaviourally distinct manner as compared to controls. The examined groups were: non maternally deprived (NMD)/sham lesioned, NMD/lesioned, maternally deprived (MD)/sham lesioned, MD/lesioned with and without the open field test. At 3 months MD/sham lesioned animals showed a marked decrease in ambulation (P < 0.01), and with ADTN lesion, the rearing values were lower (P < 0.01) and grooming higher (P < 0.05) than NMD. This last data would indicate a high emotional index. Regarding the activity of the HPA axis, maternal deprivation induced a significant decrease in plasma ACTH concentration both in sham and lesioned animals (P < 0.001), and plasma Corticosterone (C) increased in sham animals (P < 0.001). This data would indicate a higher sensitivity of the adrenal glands. After the open field test ACTH and C were different between deprived and non-deprived animals depending on the ADTN lesion. Taking into consideration the increase of ACTH levels in sham lesioned MD animals exposed to the test, we could conclude that this new situation was a stressful situation. Finally in the present work, it was very difficult to relate the behavioral parameters with the endocrine data. It is known that depending on the context, corticosteroids may produce opposite effects on emotional behavior via different receptors in the brain.In summary, neonatal maternal deprivation induced alterations of behavioral patterns and affected the ADTN inhibitory influence on ACTH and C secretion.     

Interaction of some limbic structures which exert inhibitory effect on corticosterone secretion.

The interaction between limbic structures which exert inhibitory influence on corticosterone secretion was investigated in the rat. The following experiments were performed: 1) electrical stimulation at mammillary medial nucleus (MMN) in rats with lesioned anterodrosal thalami nucleus (ADTN) or intermediate tegmental area; 2) electrical stimulation at ADTN in rats with lesioned retrosplenial cortex (RC). Bilateral stimulation at MMN in ADTN or RC-lesioned rats produces an increase in plasma corticosterone concentration. In animals with lesioned RC, values of plasma corticosterone after stimulation at ADTN were higher than before stimulation. Taking into consideration that electrical stimulation of MMN or ADTN in intact rats produces a decrease in plasma corticosterone concentration, these studies demonstrate that MMN and ADTN exert inhibitory influence on corticoadrenal activity only when their projection areas remain intact.     

Evidence for increased hepatic sympathetic nerve activity resulting in hyperglycemia in response to hemorrhage-induced reflex stimulation in anesthetized dogs

To investigate the role of the sympathoadrenal system in glucose mobilization by the liver during hemorrhage, catecholamine (CA) output from both adrenal glands was determined in anesthetized dogs. Venous blood draining from both adrenal glands was combined in a Y-tube that was connected to an electromagnetic flow probe to measure total adrenal venous blood flow. Plasma concentrations of norepinephrine (NE), epinephrine (E), dopamine (DA), and glucose (GL) were determined in various vascular regions. Adrenal CA output (nanograms per minute) under basal conditions was 50.2 +/- 13.6, 181.4 +/- 41.9, and 13.7 +/- 4.8 for NE, E, and DA, respectively. These values were found to increase significantly (P less than 0.05) in response to 5 min of hemorrhage, reaching a maximum output (nanograms per minute) of 663.6 +/- 160.6 (NE), 2503.4 +/- 607.8 (E), and 141.7 +/- 43.7 (DA). Aortic CAs (nanograms per millilitre) increased significantly with a predominant increase in E (0.33 +/- 0.08 to 3.75 +/- 1.03, P less than 0.05). In contrast, increases in portal and hepatic venous CAs (nanograms per millilitre) were characterized by a predominant increase in NE (0.30 +/- 0.06 to 0.64 +/- 0.11 and 0.17 +/- 0.02 to 0.31 +/- 0.07, respectively, P less than 0.05). Hepatic venous and aortic GL concentrations also increased significantly during hemorrhage. Among the various correlations between plasma CA and GL concentrations, the strongest correlation was found between hepatic venous NE and hepatic venous GL (r = 0.804, P less than 0.001). Correlation coefficients obtained with aortic NE and E were weaker but significant (r = 0.603 and r = 0.608, respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of central GABAA receptors suppresses the alteration of plasma catecholamine levels induced by neostigmine or histamine in rats

We investigated the effects of intraventricular injection of muscimol, the GABA_A receptor agonist, on the alteration of plasma epinephrine (E) and norepinephrine (NE) levels induced by neostigmine or histamine in anesthetized rats. Injection of neostigmine (10 nmol) into the third cerebral ventricle increased plasma levels of E more than NE, while histamine (500 nmol) increased plasma levels of NE more than E. Concomitant injection of muscimol (2.5 nmol) with neostigmine or histamine significantly suppressed the alteration of E and NE levels induced by neostigmine or histamine. These findings suggest that activation of central cholinergic neuron stimulates the adrenal medullary response more than the sympathetic nervous system, while activation of central histaminergic neuron stimulates the sympathetic nervous system more than the adrenal medullary response in anesthetized rats. Activation of GABA_A receptors in the CNS suppresses these effects.     

Oxytocin inhibits ACTH and peripheral catecholamine secretion in the urethane-anesthetized rat

Oxytocin (OT) generally has a stimulatory effect on ACTH secretion both in vitro and in vivo. As part of a study of ACTH-releasing factors in hypophysial portal blood, the effects of i.v. OT administration on plasma ACTH levels were tested in urethane-anesthetized rats. Surprisingly, i.v. injection of 10 micrograms OT lowered plasma ACTH levels by about 35% (P less than 0.01). It was reasoned that this paradoxical inhibition of ACTH secretion by OT might be mediated by inhibition of the unusually high rate of peripheral catecholamine secretion in this model. Measurement of plasma catecholamines before and after i.v. administration of 10 micrograms OT revealed a 53% inhibition of EPI (P less than 0.01) and 43% inhibition of NE (P less than 0.05). Administration of the beta-adrenergic antagonist propranolol (400 micrograms) 15 min before the beginning of the experiment completely blocked the inhibitory effects of OT on ACTH secretion and in fact unmasked the stimulatory effects of OT normally seen in conscious animals and in vitro. Superfused bisected adrenal glands exposed to 10(-6) M OT for 10 min secreted more than 30% less EPI and NE than control adrenals suggesting that the inhibition of EPI and NE secretion by OT in vivo occurs, at least in part, directly at the level of the adrenal. The data support the hypothesis that peripheral catecholamines may at times be directly involved in the control of ACTH secretion and also suggest that OT, which has recently been identified in the adrenal medulla, may have important paracrine functions in the regulation of adrenal catecholamine secretion.     

Effects of unilateral labyrinthectomy on the norepinephrine content in forebrain and cerebellar structures of albino rats

Albino (Wistar) rats were used to investigate whether unilateral labyrinthectomy (UL) modified the concentration of norepinephrine (NE) as well as of dopamine (DA) and the corresponding metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) in different areas of the cerebral and the cerebellar cortex and the striatum. The results obtained in 38 rats submitted to UL were compared to those of 18 rats submitted to sham-operation. The animals were operated under sodium pentobarbital anesthesia and sacrificed 1.5, 3 and 6 h after surgery. All rats submitted to UL showed phenomena of deficit (1.5-3 h after the lesion) followed by partial vestibular compensation (3-6 h after the lesion). Significant changes in the content of NE were neither found in different areas of the cerebral and the cerebellar cortex, nor in the striatum of rats sacrificed 1.5 h after UL. Three h after the lesion a bilateral increase in the NE content occurred in all the explored areas of the cerebral cortex (i.e., frontal, parieto-temporal and occipital) and the cerebellar cortex (i.e., the vermis and flocculus), as well as in the striatum. This increase, however, was more prominent in the parieto-temporal areas of the neocortex of the intact side, in all the explored areas of the cerebellar cortex of that side, as well as in the striatum of the lesioned side. This asymmetric increase in NE content could not be attributed, at least exclusively, to a generalized activation of the noradrenergic LC nuclei of both sides, due to waking and/or stress which may occur after UL, but did rather depend on asymmetric changes in unit discharge of the vestibular nuclei projecting to the LC of both sides, following UL. In particular, the increased discharge of the vestibular nuclei of the intact side would lead to activation of noradrenergic neurons projecting particularly to the parieto-temporal cortex and the cerebellar cortex of the intact side, as well as to the striatum of the lesioned side. A bilateral increase in NE content was still observed in different areas of the cerebral and cerebellar cortex of rats sacrificed 6 h after UL. This increase, however, was of smaller entity than that observed in the same areas 3 h after UL and quite symmetric. The content of DA and its metabolite DOPAC decreased bilaterally in the striatum of rats sacrificed 1.5 h after UL. This effect was attributed to a reduced synthesis and release of DA, which probably resulted from a reduced facilitatory influence that the deafferented vestibular nuclei exert on the dopaminergic, nigrostriatal system of both sides, although mainly on the intact side. The corresponding values, however, bilaterally recovered to slightly increase with respect to the control values in rats sacrificed 3 and 6 h after UL. In these experiments the content of both DA and DOPAC remained symmetric on both sides after UL, in contrast with the bilateral but asymmetric increase in NE concentration observed in the same structure 3 h the lesion. The present results integrate and extend those of previous experiments showing that: 1) albino rats sacrificed 6 h after UL displayed an increased synthesis of NE, which affected particularly the LC of the intact side as well as the medial vestibular nuclei of both sides (21); and 2) the structures which showed an increased content of NE at given time intervals after UL also displayed an increase in the expression of the immediate early gene c-fos (cf. 16 for ref.). These findings suggest that bilateral but asymmetric activation of the noradrenergic LC neurons following UL may lead to an asymmetric increase in c-fos expression in several target structures, thus contributing to the plastic changes responsible for vestibular compensation. In conclusion, it appears that UL induces in several brain structures of albino rats a short-term increase in synthesis and release of NE. (ABSTRACT TRUNCATED)     

L-NAME raises systolic blood pressure in the pithed rat by a direct adrenal epinephrine releasing action

It is generally thought that inhibition of nitric oxide synthase leads to blood pressure elevation largely through reduction in vascular levels of the vasodilator nitric oxide. However, there are several reports suggesting that NO synthase inhibitors cause adrenal epinephrine (E) release by both central and peripheral mechanisms. We investigated the role of adrenal E in the pressor effects of the nitric oxide synthase inhibitor L-NAME in the pithed rat to help distinguish central from peripherally mediated actions. L-NAME (10 mg/kg) raised both systolic and diastolic BP by about 30 mm Hg (P < .01) in the absence of exogenous electrical stimulation of sympathetic nerves. During stimulation at 10 V and frequencies of 1 or 2 Hz, systolic BP was about 70 mm Hg higher in L-NAME treated rats than in drug free stimulated rats. This enhancement of systolic BP by L-NAME was less pronounced at 5 or 10 Hz stimulation frequencies. Following these types of electrical stimulations of pithed rats, both plasma norepinephrine (NE) and E levels were dramatically elevated above resting plasma levels. L-NAME pretreatment of these electrically stimulated rats increased plasma E levels by an additional 60% and decreased NE by 18%. Acute adrenalectomy dramatically reduced plasma E levels and abolished the ability of L-NAME to enhance the pressor effect of sympathetic stimulation. In contrast, acute adrenalectomy of unstimulated pithed rats did not significantly reduce the pressor response to L-NAME. We conclude that adrenal E release may mediate much of the systolic pressor response of L-NAME in the stimulated pithed rat, but the magnitude of this effect varies with stimulation frequency. Since pithing disrupts central pathways, this induction of adrenal E release by L-NAME is a peripheral effect.     

The effect of paragigantocellularis lateralis lesion on conditioned place preference (CPP) in presence or absence of alpha2 adrenergic agonist (clonidine) in male rats

The nucleus paragigantocellularis lateralis (LPGi) is located in the rostral ventrolateral medulla (RVLM), a brain stem region that regulates homeostatic functions such as blood pressure and cardiovascular reflexes, respiration, pain and opiate withdrawal syndrome. LPGi has many anatomical relationships with important nuclei such as arcute nucleus, caudal raphe nucleus, periaqueductal gray (PAG), locus coeruleus (LC), and dentate. In this study we have examined the role of LPGi in the conditioned place preference (CPP) induced by morphine in the presence and absence of clonidine in the rat. We used 49 male N-MRI rats which were divided into 7 groups randomly: 1: Control, 2: Control+saline, 3: sham control, 4: lesion, 5: lesion +0.02 mg/kg clonidine, 6: lesion +0.2 mg/kg clonidine, 7: lesion +2 mg/kg clonidine. Animals were anaesthetized with ketamine (110 mg/kg) and rampune (Xylazine) (3 mg/kg) mixture. In the process of surgery LPGi nucleus has been destroyed bilaterally by DC electrical current (1 mA, 6 second), with stainless steel electrode placed in stereotaxic coordinates of (AP = 11.8, Lat +/- 1.86 and Depth = 10.5). After the recovery period, they were treated with clonidine one hour before the application of Hand's method to induce CPP. We have not found any significant differences between the results of control, control+saline and sham groups in the CPP test but there is a significant increase in the CPP time between sham and LPGi lesion+saline groups (P < 0.019). Clonidine at different doses (0.02, 0.2 and 2 mg/kg) have decreased CPP time in LPGi lesioned group in comparison with lesioned+saline group as well (p < 0.002). In this study we have also demonstrated that clonidine has not any effects on the CPP time in the intact animals. Our results indicate that LPGi lesion induces CPP. It seems that LPGi is involved in drug reinforcements and also LPGi lesion induces sensitivity to alpha2 adrenergic agonist.     

Plasma catecholamine concentrations in normotensive rats of different strains and in spontaneously hypertensive rats under basal conditions and during cold exposure

Under basal conditions, the levels of circulating norepinephrine (NE) and epinephrine (E) were higher in normotensive Wistar rats of different origins than in Sprague-Dawley rats. Since the decline of ³H-NE concentration in the plasma after i.v. injection was similar in Wistar and in Sprague-Dawley rats, the higher levels of endogenous NE in the former strain probably reflect greater NE release from sympathetic nerve terminals. In normotensive Sprague-Dawley and Wistar rats, plasma NE rose to various extents during cold exposure (4°C), depending on the basal plasma NE levels. Compared with normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) had similar basal plasma E and NE concentrations, similar rates of ³H-NE disappearance, but more rapid increases to higher values of plasma NE during cold exposure. It is concluded that the basal rate of peripheral catecholamine release does not seem to be the main determining factor for arterial blood pressure in the various rat strains and that the sympathetic neuronal system of SHR is more responsive to cold exposure than that of WKY rats.     

Norepinephrine triggers medullar epinephrine depletion during normoglycemia

Our experiments did show that chronic 12 hours administration of norepinephrine (NE) to rats by means of subcutaneously implantable retard tablets, led to a highly significant epinephrine (E) depletion of the adrenal medulla during normoglycemia. The expected rise of free plasma NE at 6 and 12 hours was accompanied by increased free plasma E values at 12 hours. At this very time point the liver contents of glycogen and free intracellular glucose showed their most pronounced decrease. Since at 12 hours both liver glycogen and medullar E values were at their lowest, a second experiment was performed to examine a possible causal relationship. In order to curb the breakdown of liver glycogen, rats were force fed with 50% glucose solution 9 hours after NE tablet implantation. Glucose feeding not only caused a much less pronounced liver glycogen fall at 12 hours, but, at the same time also prevented E depletion of the adrenal medulla. These observations suggested that rapid fall of liver glycogen and/or liver intracellular free glucose might be the trigger for medullar E depletion, even before hypoglycemia.     

Effects of central GABA receptors activation on catecholamine secretion in rats

We investigated the effects of muscimol, the GABA_A receptor agonist, and baclofen, the GABA_B receptor agonist, injected into the third cerebral ventricle on plasma epinephrine (E) and norepinephrine (NE) levels in anesthetized rats. Baclofen (0.4–5 nmol) increased plasma NE levels in a dose dependent manner but did not affect plasma E levels. Muscimol (2.5 nmol) affected neither plasma E nor NE levels. Concomitant injection of muscimol (2.5 nmol) with baclofen (5 nmol) attenuated the baclofen (5 nmol)-induced NE secretion. These findings suggest that activation of GABA_B receptors in the central nervous system (CNS) stimulates the sympathetic nervous system but not the adrenal medullary response. In contrast, activation of GABA_A receptors in the CNS affects neither the sympathetic nervous system nor the adrenal medullary response, but inhibits the sympathetic neural activity induced by activation of GABA_B receptors in anesthetized rats.     

Ebselen lowers plasma interleukin-6 levels and glial heme oxygenase-1 expression after focal photothrombotic brain ischemia

Heme oxygenase-1, an inducible heat shock protein, is upregulated by oxidative stress, and its expression is modulated by proinflammatory cytokines such as IL-1 and IL-6. In the present study, we investigated the effects of postlesional, orally applied ebselen, a neuroprotective antioxidant, on serum levels of IL-6 and cerebral heme oxygenase-1 expression following focal ischemia induced by photothrombosis. Ebselen (50 mg/kg body weight) was given 30 min postlesion to male Wistar rats. Animals were divided into four groups: sham-operated vehicle control (n = 9), sham-operated ebselen control (n = 8), lesioned vehicle control (n = 14), and lesioned ebselen-treated (n = 17). Ebselen treatment resulted in a significant lowering of IL-6 plasma levels (26 +/- 5 pg/ml) as compared with that seen in lesioned vehicle controls (48 +/- 9 pg/ml) at 24 h postlesion. In sham-operated rats IL-6 was not detectable. Heme oxygenase-1-positive glial cells were quantitated within topographically determined perilesional brain regions. Within the 0.5-mm-wide rim region directly associated with the lesion core, no differences in the amount of heme oxygenase-1-positive glial cells were found. However, in the more remote ipsilateral perilesional cortex, significantly fewer heme oxygenase-1-positive glial cells were present within the supragranular cortical layers of lesioned ebselen-treated rats compared to lesioned vehicle controls (P < 0.001). In sham-operated rats, no glial heme oxygenase-1 induction occurred. The results indicate that postlesional ebselen treatment lowered plasma IL-6 levels subsequent to a photothrombotic lesion concomitant with a lowering of the heme oxygenase-1 response in glial cells.     

A comparative study of adrenal progesterone secretion during the estrous cycles of hamsters and rats

Adrenal secretory rates and peripheral plasma levels of progesterone (PROG) were determined during the estrous cycles of hamsters and 4-day cyclic rats. In both species, the PROG concentrations in peripheral plasma were never more than 6% of those observed in adrenal venous plasma. In hamsters, adrenal PROG secretory rates varied from 3.8 ± 0.8 ng/min at 0800 hr on proestrus (P) to 8.5 ± 1 ng/min at 2000 hr on estrus (E). The rates noted on P were among the lowest observed and were similar to those noted at 0800 hr the following morning. In rats, adrenal PROG secretory rates varied from 57 ± 9 ng/min at 0800 hr on E to 130 ± 18 ng/min at 2000 hr on P. A significant decline occurred between 2000 hr on P and 0800 hr the following morning. Rats secreted 3 to 8 times more PROG than did hamsters when the secretory rates are expressed as ng/min/100 mg adrenal. In hamsters, the data suggest a relative lack of influence of female reproductive hormones on adrenal PROG secretion and in turn the latter may not be involved in reproductive hormonal changes leading to ovulation. In rats, the increased adrenal PROG secretion noted on P may be due to the influence of reproductive hormones on adrenocortical function. This elevated rate may in turn influence the hypothalamo-hypophyseal-ovarian axis.     

R?le of histamine on plasma fibrinogen levels in rats with surgical injury (laparotomy)

The probable r?le of endogenous histamine in the increase of plasma fibrinogen in rats submitted to tissue injury (laparotomy) was studied. In laparotomized rats with 10 mg kg-1 day-1 of diphenhydramine (a H1-histamine receptor blocker) plasma fibrinogen decreased significantly as compared to the group of rats laparotomized only (P less than 0.02), reaching values similar to those observed in rats laparotomized with removal of the adrenal medulla or laparotomized with severing of splanchnic nerves. There is a significant difference between these latter groups and the normal noninjured group (P less than 0.01). Plasma fibrinogen did not modify (as compared with the uninjured group) in rats injected only with histamine (1 mg kg-1 day-1) or with diphenhydramine. Taking into account the results obtained and the mechanism of action of diphenhydramine, it would seen that endogenous histamine takes part in the increase of plasma fibrinogen in laparotomized rats, perhaps indirectly through stimulation of the adrenal medulla secretion.     

Effects of estrogens and progesterone on the catecholaminergic activity of the adrenal medulla in female rats

Some reports in the literature allow to suspect the existence of an effect of sexual steroids on the adrenal catecholamines. To test this possibility, we have examined the catecholaminergic activity in the adrenal medulla of normal cycling rats in three phases of estrous cycle and of ovariectomized (OVX) rats injected with pharmacological doses of estradiol (ES), 2-hydroxyestradiol (HE) and/or progesterone (P). Adrenomedullary content of norepinephrine (NE) was similar during the estrous cycle, while epinephrine (E) content was increased during diestrous. This increase was concomitant with an increased phenylethanolamine-N-methyltransferase (PNMT) activity. Moreover, the monoamine oxidase (MAO) activity was significantly increased during proestrous, while the catechol-O-methyltransferase (COMT) activity was significantly decreased during estrous. In addition to these observations, ovariectomy caused a significant reduction of the E/NE ratio and of COMT and MAO activities. Administration of ES to OVX rats increased the E content, the E/NE ratio and the COMT activity as compared to vehicle-treated OVX rats. Administration of P to OVX animals led also to a significant increase of the E/NE ratio and of the COMT activity but not of the E content, while the administration of this steroid to OVX rats previously treated with ES only increased the COMT activity. Finally, administration of HE caused non-significant changes in NE and E contents and in MAO, COMT and PNMT activities. We can conclude that sexual steroids seem to be able to modify the catecholamine metabolism in the adrenal medulla and, hence, they could alter the ability of this gland to store and release these amines.     

Epinephrine and dopamine colocalization with norepinephrine in various peripheral tissues: guanethidine effects

Chemical sympathectomy with guanethidine (Gnt) selectively destroys the postganglionic noradrenergic neurons, whereas dopaminergic fibers and nonneural catecholamine-secreting cells are spared. As a result, the relative proportions of norepinephrine (NE), epinephrine (E), and dopamine (DA) in tissues can be differentially affected. This study was done to show the possible differences in the relative amount of catecholamines in some organs and tissues that might indicate the nature of the secretory cells from which they originate. The contents of NE, E, and DA were assessed in rats neonatally treated with Gnt. Gnt-treated rats showed significantly lower levels of NE (P < 0.01) in all tissues except the adrenal gland and paraganglia. Epinephrine was present in all tissues with mean levels below 25 ng/g, with the exception of the adrenal gland (700 microg/gland) and paraganglia (100 ng/g). Only the heart showed lower values in Gnt-treated rats. Mean DA levels were also very high in paraganglia (530 ng/g). In the Gnt-treated rats, DA levels fell practically to zero except in the duodenum, mesentery, and adrenal, whereas there were high levels in the paraganglia, which were significantly different from controls. The results suggest that the three catecholamines are contained mainly in noradrenergic sympathetic fibers of muscle, white adipose tissue, heart, liver, pancreas, and spleen. The duodenum and mesentery may have dopaminergic fibers or E- and DA-containing nonneural cells. Hepatic-vagus paraganglia contain all the catecholamines in relatively high amounts in nonneural cells, and Gnt treatment raises DA levels without affecting the other amines.     

Sympatho-endocrine and metabolic responses to exercise under post-ganglionic blockade in rats

The purpose of this study was to further document the role of locally released norepinephrine (NE) in the control of metabolic and endocrine responses to exercise in rats. Post-ganglionic blockade with bretylium (20 mg.kg-1, i.v.) reduced NE release from sympathetic nerve endings and triggered a compensatory increase in epinephrine (E) release from the adrenal medulla, as reflected by plasma NE and E concentrations at rest and exercise (E/NE ratio = 2.92 +/- 0.53 and 2.48 +/- 0.51 vs 0.62 +/- 0.15 and 1.48 +/- 0.18 in control rats; mean +/- SE). Following bretylium administration a reduction in running time to exhaustion (28 m.min-1, 8% slope: 33 +/- 2 min vs 74 +/- 10 min) was associated with 1) a faster decrease in blood glucose concentration (3.58 +/- 0.80 mM vs 8.09 +/- 0.38 mM in control rats exercised for 33 min); and 2) an increased glycogen store utilization in fast-twitch muscles (superficial vastus lateralis and gastrocnemius lateralis). Glycogen utilization was not modified in soleus muscle and in the liver. Taken together these results suggest that post-ganglionic blockade increased carbohydrate store and peripheral blood glucose utilization. This could reflect an impairment in fat mobilization and utilization which might be secondary to a reduction of NE release in the adipose tissue and/or in the endocrine pancreas.     

Plasma catecholamine responses to tyrosine hydroxylase inhibition and cold exposure

The acute effect of α-methyl-p-tyrosine (αMPT), a tyrosine hydroxylase inhibitor, on plasma levels of norepinephrine (NE), epinephrine (E), dopamine (DA), and adrenal cholesterol content in male rats at room temperature (24°C) and during acute cold exposure (4°C) was evaluated. Compared to saline-treated controls, αMPT: 1) significantly reduced plasma NE and DA in both normal and cold stress conditions, 2) significantly increased plasma E in both environments, and 3) stimulated the adrenal cortex. These findings suggest that tyrosine hydroxylase inhibition and consequent catecholamine synthesis blockade disrupts the homeokinesis of adrenergic processes and may present a significant stress to the intact animal.     

Rotation produced by administration of dopamine and related substances directly into the supersensitive caudate nucleus

Dopamine and related compounds were administered directly into the caudate nucleus ipsilateral to a unilateral 6-OHDA induced lesion of the substantia nigra in rats. Dopamine, norepinephrine, epinine, epinephrine, apomorphine and ADTN produced vigorous long-lasting, dose-related contraversive circling. Dopamine was the most potent substance tested, its threshold for significant activity was 0.06 μg and the dose producing the maximal rate of rotation was 0.40 μg. Serotonin produced modest rotation which was not dose-related. Piribedil, although more effective than its metabolite S584, produced only a short period of activity at very high doses. Isoproterenol and clonidine were inactive.The effects of dopamine were compared in lesioned and non-lesioned rats. The supersensitivity of the lesioned rats was manifested as an increase in the potency of dopamine and as an increase in the maximal response, defined as rate of rotation. Rotation was produced in non-lesioned rats only after pretreatment with tranylcypromine, which had no significant effect in lesioned rats.