Brainstem Norepinephrine Research Articles

Effects of acute hypoxia on neonatal rat brain: Regionally selective, long-term alterations in catecholamine levels and turnover

Neonatal rats were exposed to 2 hr of hypoxia (7% O 2) on the day after birth and examined for effects on development of noradrenergic and dopaminergic systems. Measurements were made of transmitter levels and turnover, the latter a biochemical index of neuronal activity. Hypoxia had a regionally selective effect, characterized by a long-lasting increase in turnover of norepinephrine and dopamine in midbrain and brainstem, with little or no effect in cerebral cortex or cerebellum. The effects of hypoxia were exacerbated when peripheral α-adrenergic receptors were blocked with phenoxybenzamine during the hypoxic exposure; in this case, the same abnormalities were then seen in the cerebral cortex as well. Thus, the release of peripheral catecholamines during the hypoxic insult, and their actions at α-adrenergic receptors, may play a role in protecting the neonatal nervous system from hypoxia-induced alterations.

Modulation by Norepinephrine of Neural Responses to Estradiol

Pharmacological studies have suggested that neurotransmitter activity impinging on steroid-concentrating cells can affect the steroid receptor system within those cells, modifying behavioral responses to the hormone. The present experiments revealed that the alpha 1-noradrenergic antagonist prazosin, administered to ovariectomized rats at the time of each of two pulses of estradiol, inhibited the appearance of sexual receptivity. Prazosin also substantially reduced the levels of estrogen receptors within hypothalamic cell nuclei following an injection of estradiol. Manipulation of noradrenergic inputs into the hypothalamus by lesioning brain stem norepinephrine cell groups with 6-hydroxydopamine (6OHDA) also reduced the level of nuclear estrogen receptors following an injection of estradiol. Although this effect of 6OHDA lesions was observed in two separate experiments, in other experiments 6OHDA had no effect on estrogen receptors. In some instances, there was a positive correlation between nuclear estrogen receptor levels in the hypothalamus and the levels of norepinephrine. The results are consistent with the hypothesis that brain stem inputs to the hypothalamus are able to modulate neural responses to steroids and specifically that noradrenergic inputs are able to modulate neural responses to estradiol. However, there are additional undiscovered variables that preclude statements of a simple relationship between norepinephrine levels and estrogen receptor levels.

Neural-Renal Interactions in the Hypertension Induced by Papillary Necrosis: Role of Dietary Salt Intake

The effects of high salt intake (1.0% NaCl in the drinking water) on rats made hypertensive by 2-bromoethylamine hydrobromide (BEA) treatment (200 mg/kg, i.p.) were examined. BEA-induced medullary necrosis resulted in a mild hypertension (146 +/- 5 mm Hg) that was exacerbated by 4 weeks of high salt intake (163 +/- 6 mmHg). BEA-treated rats had significant salt-induced increases in urinary norepinephrine excretion and hypothalamic and brainstem norepinephrine content, that were not present in BEA-treated rats drinking tap water or control rats drinking saline. BEA treatment in combination with increased salt intake produced a decrease (p less than 0.05) in renal dopamine content and adrenal norepinephrine stores relative to BEA treatment alone. BEA treatment also significantly decreased renal norepinephrine stores and dopamine binding sites irrespective of salt intake. Renal alpha 2-adrenergic receptors and central nervous system stores of dopamine and serotonin were unaffected by BEA treatment. Renal function was well preserved as indicated by normal creatinine, glucose and protein excretion; however, significant (p less than 0.05) disruption of the urinary concentrating mechanism was present. These studies suggest that BEA-induced hypertension has a neural component that is exacerbated by high salt intake. The primary defect in BEA hypertension appears to be the lack of circulating antihypertensive lipids that attenuate the ability of salt loads to simulate sympathetic nervous system activity.

Central catecholaminergic responses in hypoxie moderation of spontaneous hypertension

Exposure to hypobaric hypoxia (H; simulated altitude = 3658 m) was initiated in 5-week-old, male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKy) normotensive rats while normoxic controls (N) for both groups were maintained under laboratory conditions. Significant attenuation of systolic arterial blood pressure was evident in SHR-H relative to SHR-N (125 ± 6 vs. 145 ± 5, mmHg; p < 0.05) while blood pressure in the normotensive, Wistar-Kyoto rat was not affected by 20 days of exposure to hypoxia (WKy-H, 116 ± 2 vs. WKy-N, 117 ± 5, mmHg). Increased contents of norepinephrine and dopamine in brain stem, striatum, hypothalamus, and frontal cortex in SHR versus WKy indicated a possible involvement of central Catecholaminergic mechanisms with spontaneous hypertension. Hypoxia significantly decreased neuronal contents of both neurotransmitters, typically on both days studied (days 4 and 21 of altitude treatment). In striatum and hypothalamus, dihydroxyphenylacetic acid to dopamine ratios indicated that dopamine turnover was decreased with hypoxia. Hypoxia elicits Catecholaminergic responses consistent with profiles found following ICV administration of 6-hydroxydopamine, a sympatholytic agent that also prevents the development of spontaneous hypertension. Hypoxic mitigation of spontaneous hypertension may occur via mechanisms initiated at the level of the CNS.

Effects of CI-926 (3-[4-[4-(3-Methylphenyl)-l-Piperazinyl] Butyl]-2,-4-Imidazolidinedione), an Antihypertensive Agent, on Rat Brain Catecholamine and Serotonin Turnover

The effects of the antihypertensive drug CI-926 on rat brain norepinephrine (NE), dopamine (DA), and serotonin (5-HT) turnover and its in vitro affinity for several receptors were investigated. CI-926 (3-30 mg/kg intraperitoneally, i.p.) caused a dose-dependent increase in the rate of brain stem NE synthesis and increased the decline in NE after inhibition of its synthesis by alpha-methyl-p-tyrosine. These findings indicated that CI-926 increased brain NE turnover, probably as a compensatory response to central adrenoceptor blockade based on its nanomolar affinity for alpha 1-adrenoceptors and micromolar affinity for alpha 2-adrenoceptors. CI-926 also increased the rate of DA synthesis and DA metabolite levels; this indicates an increase in DA turnover. The latter effect of CI-926 is attributed to a compensatory response to DA-2 receptor blockade because no affinity for DA-1 relative to DA-2 receptors was found and the effect was antagonized by the DA agonist pergolide. CI-926 decreased brain 5-HT turnover, as indicated by reduced concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid and a reduced rate of 5-HT synthesis, effects characteristic of centrally acting 5-HT agonists. Based on its affinity for 5-HT-1A receptors versus 5-HT-1B and 5-HT-2, the decrease in 5-HT synthesis and release is interpreted as evidence of 5-HT-1A receptor activation. These findings indicate that besides peripheral alpha 1-adrenergic blockade, an interference of CI-926 with central adrenergic and serotoninergic neurotransmission may contribute in part to an explanation of its antihypertensive properties.

Stress and behavior in streptozotocin diabetic rats: Biochemical correlates of passive avoidance learning.

Retention of one-trial passive avoidance training was compared in diabetic and nondiabetic rats. Also compared were corticosterone concentrations associated with both training and retention testing, catecholamine excretion related to training, and regional brain catecholamine concentrations accompanying retention testing. Diabetic rats showed significantly better retention for the task than did nondiabetic rats. Associated with retention differences, diabetic rats had higher epinephrine excretion and nondiabetic rats had lower excretion after footshock training relative to baseline measures. Norepinephrine excretion was elevated in diabetics both in baseline measurement and during the 24 hr following footshock training. No differences were found in baseline or stimulated corticosterone concentration between diabetic and nondiabetic rats. Diabetic rats had higher concentrations of norepinephrine (NE) and dopamine (DA) and lower 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in hypothalamus and higher NE in brain stem and amygdala than did nondiabetics, although both diabetic and nondiabetic rats had reduced DA and NE following retention testing. The results indicate that there are biochemical alterations in diabetes that may have important behavioral impact.

Biochemical evidence that brainstem adrenaline-containing neurons are activated during clonidine withdrawal in the spontaneously hypertensive rat.

We have investigated the effects of prolonged treatment with clonidine (delivered intravenously via osmotic minipumps, 0.1 mg/kg/day for 7 or 10 days) and of withdrawal of such treatment on brainstem noradrenaline and adrenaline metabolism in the adult spontaneously hypertensive rat (SHR). After a seven day treatment with clonidine, noradrenaline and adrenaline turnovers were unchanged both in the A2-C2 and A1-C1 regions. During withdrawal, the noradrenaline turnover was also unchanged in these regions. However, the adrenaline turnover was significantly increased 16 h after withdrawal (p less than 0.01) in the A2-C2 region and 16 h (p less than 0.01) and 40 h (p less than 0.05) after withdrawal in the A1-C1 region. These results show that noradrenaline metabolism is unchanged both during clonidine treatment and during its withdrawal in the brainstem catecholaminergic regions analyzed. In contrast, the increases in adrenaline turnover found in the A2-C2 and A1-C1 regions suggest that the adrenergic neurons of the brainstem could be activated during clonidine withdrawal. As the adrenergic C1 neurons are a key element of the sympathetic vasopressor system, the increase in adrenaline turnover observed during withdrawal could be at the origin of the sympathetic hyperactivity found after cessation of prolonged treatment with clonidine.

Abnormalities in hypothalamic and neurohypophysial vasopressin content are not a consequence of hypertension in the spontaneously hypertensive rat

In order to determine if the decreased hypothalamic and increased posterior pituitary content of vasopressin (VP) observed previously in spontaneously hypertensive rats (SHR) were a secondary consequence of the hypertension, the effect of preventing the development of hypertension on VP content of the hypothalamoneurohypophyseal system was evaluated. Two methods for preventing the hypertension were used: (1) chronic angiotensin-converting enzyme inhibition (oral captopril, 100 mg/kg/day at 4–12 weeks of age); and (2) intraventricular 6-hydroxydopamine (6-OHDA, 200 μg at 4 and 5 weeks of age). Both of these treatments markedly attenuated the increase in systolic blood pressure in SHRs at 5–11 weeks of age. The captopril-treated rats had a significant elevation in serum renin activity at 12 weeks of age indicating the presence of chronic converting enzyme inhibition, and the 6-OHDA-treatment resulted in a depletion of hypothalamic (86%) and brainstem (76%) norepinephrine content. Hypothalamic VP content was reduced in untreated SHRs compared to normotensive Wistar-Kyoto rats (WKYs, P = 0.0015). It was not significantly altered in either strain by the 6-OHDA treatment. Captopril caused a reduction in hypothalamic VP content in both SHRs and WKYs ( P<0.01). Posterior pituitary VP content was elevated in untreated SHRs compared to WKYs ( P<0.001), and remained elevated with captopril and 6-OHDA treatments. These data indicate that the abnormalities in VP content in the hypothalamus and posterior pituitary of SHRs are not a response to the hypertension. Therefore, they may represent primary abnormalities in the SHR. In contrast, the suppression of renal renin concentration previously observed in SHRs was abolished when the hypertension was prevented by 6-OHDA treatment suggesting that the reduced renin concentration in mature SHR is a secondary response to the hypertension.

Monoamine alterations during experimental hydrocephalus in neonatal rats.

The present study was designed to determine the selected monoamine changes that occur during infantile hydrocephalus. Obstructive hydrocephalus was induced in newborn rats by injection of a suspension of kaolin into the 4th ventricle and cisterna magna. Eleven days later, experimental animals and their sham-operated littermate controls were killed and pieces of frontoparietal cortex, neostriatum, cerebellar vermis, and brain stem were processed for high performance liquid chromatography. Grossly, the lateral ventricles were extremely enlarged, the cerebral cortex was thinned, the neostriatum was compressed, and portions of the tectum and cerebellum were vacuolated. Decreases in norepinephrine (71%), dopamine (73%), and serotonin (50%) were observed in the cerebral cortex, neostriatum, and cerebellum, respectively. Brain stem norepinephrine and serotonin were increased 70% and 50%, respectively. These increases may indicate impairment of axonal transport or damage to projections from the locus ceruleus and raphe region. These preliminary results suggest that infantile hydrocephalus causes perturbations in the levels of different monoamines in several brain regions. Such changes may critically influence neuronal function and development, as well as the therapeutic management of hydrocephalus.

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.

Depletion of brainstem epinephrine stores by α-methyldopa: Possible relation to attenuated sympathetic outflow

The antihypertensive effect of α-methyldopa (MD) is believed to be critically dependent on its ability to deplete endogenous catecholamines or cause the synthesis of false neurotransmitters. We used liquid chromatography with electrochemical detection (LCEC) and negative chemical ionization gas chromatography-mass spectrometry (GC-MS) for quantitation of catecholamines and MD metabolites in rat. MD intraperitoneally (100 mg/kg q12 hr × 12 days), significantly increased α-methylnorepinephrine (MNE) in brain (1.02 ± 0.33 μg/g), heart (1.67 ± 0.57 μg/g) and adrenal glands (114.93 ± 50.47 μg/g) Endogenous norepinephrine (NE), epinephrine (E) and dopamine (DA) were reduced. ME levels were 2.19 ± 0.44 μg/g (n=6) in the adrenal gland but only 99 ± 26 pg/g (n=3) in the brainstem. MD-induced endogenous brainstem NE depletion was more than compensated by MNE production, but brainstem E depletion was not compensated for by a stoichiometric production of brainstem ME.

Corticotropin-releasing factor administration elicits a stress-like activation of cerebral catecholaminergic systems

The cerebral content of the biogenic amines, dopamine (DA), norepinephrine (NE), and serotonin (5-HT) and their catabolites 30 min after CRF or saline injections was determined using HPLC with electrochemical detection. Injection of CRF (1.0 μg) into the lateral ventricles (ICV) of mice produced a behavioral activation in which their motor movements appeared as bursts of activity followed by periods of immobility. CRF administration (ICV or SC) did not alter the concentrations of DA, NE, tryptophan, 5-HT, or 5-hydroxyindoleacetic acid (5-HIAA) in any brain region measured. ICV CRF increased the concentrations of dihydroxyphenylacetic acid (DOPAC), the major catabolite of DA, and of 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG), the major catabolite of NE, in several brain regions. DOPAC:DA ratios were consistently increased in prefrontal cortex, septum, hypothalamus, and brain stem relative to animals injected with saline. MHPG:NE ratios were also increased in the prefrontal cortex and hypothalamus, with a marginal effect ( p=0.06) in brain stem. SC CRF significantly increased DOPAC:DA in prefrontal cortex, and MHPG:NE in prefrontal cortex, hypothalamus and brain stem. Pretreatment with naloxone did not prevent any of the neurochemical responses to ICV CRF, but naloxone alone increased DOPAC:DA in medial profrontal cortex, and decreased MHPG:NE in nucleus accumbens in CRF-injected mice. These results suggest that administration of CRF either centrally or peripherally induces an activation of both dopaminergic and noradrenergic systems in several regions of mouse brain. The pattern resembles that we observe in mice following stressful treatments such as footshock or restraint, but the effect of CRF on noradrenergic systems is less pronounced. Also, brain free tryptophan which is consistently increased in all brain regions by footshock or restraint was not altered by CRF. Thus CRF triggers a response in CNS catecholamine systems that resembles, but does not precisely mimic, that observed following commonly used stressors. This activation of CNS catecholamine metabolism may be related to some of the behavioral effects of CRF, but not all of them because naloxone, which prevents the effects of CRF on exploratory behavior, did not alter the catecholamine responses to CRF.

Kindling antagonism: a role for hindbrain norepinephrine in the development of site suppression following concurrent, alternate stimulation

The concurrent, alternate electrical stimulation of the septal nucleus and the entorhinal cortex results in the development of fully generalized seizures at one site (dominant site) and the lack of development of kindled seizures at the other (suppressed or antagonized site). We have labeled this phenomenon kindling antagonism. Previous work from our laboratory has demonstrated that the whole brain depletion of norepinephrine (NE) eliminates the development of kindling antagonism 1. In the present study animals were treated with the neurotoxin 6-hydroxydopamine (6-OHDA) as neonates. The neonatal administration of 6-OHDA produced robust increases in brainstem and cerebellar NE levels and depletions of forebrain NE levels when assayed at maturity. Striatal dopamine levels were spared by this treatment. Neonatal 6-OHDA did not alter the development of the kindling antagonism phenomenon which is typically observed following concurrent, alternate stimulation of the septal nucleus and entorhinal cortex. Neonatal 6-OHDA treatment significantly facilitated the rate of kindled seizure development at dominant sites but failed to alter thresholds for the elicitation of afterdischarges (AD) or patterns of development of AD durations. Other characteristics of kindling antagonism were similarly unaffected by 6-OHDA treatment. These data suggest that brainstem and/or cerebellar NE are sufficient to mediate the development of kindling antagonism in the relative absence of forebrain NE.

Changes in plasma corticosterone and cerebral biogenic amines and their catabolites during training and testing of mice in passive avoidance behavior

Concentrations of cerebral biogenic amines and their catabolites, and of plasma corticosterone were determined 10 min after training and testing of passive avoidance behavior in mice. Training and testing of mice that had acquired the task well resulted in statistically significant increases of plasma corticosterone, of the DOPAC:DA ratio [an index of dopamine (DA) metabolism] in prefrontal cortex, and of MHPG:NE ratios [an index of norepinephrine (NE) metabolism] in hypothalamus and brain stem. There were also decreases of NE in hypothalamus and brain stem, and an increase of 5-HIAA:5-HT [an index of serotonin (5-HT) metabolism] and of tryptophan in brain stem. Some of these changes also occurred in mice merely exposed to the apparatus but not trained. Plasma corticosterone concentrations were significantly higher in mice that performed the task well compared to those that did not, and there were significant correlations between this measure and the avoidance performance. Although there was only one statistically significant correlation between a cerebral metabolite and the avoidance performance (a decrease in hypothalamic NE), there were indications of relationships between cerebral biogenic amine metabolism and the performance. The patterns of neurochemical and endocrine changes closely resemble those previously observed in response to various stressors. Thus, the changes could reflect stress responses, which may or may not be related directly to the performance of the avoidance task.

Effect of urapidil on rat brain catecholamine synthesis.

The effects of urapidil, a clinically effective antihypertensive drug, on the in-vivo rate of synthesis of rat brain noradrenaline (NA) and dopamine (DA) was determined. A significant dose-dependent increase in dopa concentration by urapidil after dopa decarboxylase inhibition by NSD 1015 was observed in brain stem (3-30 mg kg-1 i.p.) and striatum (10-30 mg kg-1 i.p.), indicating increased NA and DA turnover, respectively, most probably a result of central blockade of brainstem alpha 1-adrenergic and striatal DA receptors. These results indicate that urapidil may possibly exert its central hypotensive action in part by a reduced influence on brain stem NA, thus reducing central sympathetic outflow.

Neonatal monosodium glutamate administration alters noradrenergic measures in the brainstem of the mouse

Mice treated neonatally with MSG (4 mg/g) were compared to saline-injected controls on a number of neurochemical parameters of brainstem noradrenergic activity. MSG treatment resulted in an attenuation of brainstem norepinephrine (NE) decline after α-methyl-p-tyrosine administration. Neonatal MSG administration did not result in alterations in the steady state levels of brainstem NE or MOPEG. The synthesis of NE was slightly increased in the pons-medulla of MSG-treated mice as indexed by pargyline-induced NE accumulation. NE release, however, appeared diminished as reflected by a significant ( p < 0.05) decrease in the ratio of normetanephrine to NE found in the pons-medulla of MSG-treated mice given pargyline. The results suggest that MSG-induced damage to the arcuate nucleus produces selective alterations in brainstem NE systems. These alterations may reflect the toxic action of MSG on the opiomelanocortin neurons of the arcuate nucleus or other descending systems that are damaged by MSG. The loss of the descending opiomelanocortin input to the brainstem could result in these types of neurochemical consequences since the pharmacologie action of opiate drugs results in a selective enhancement of brainstem NE turnover in rodents.

67 The Role of Thyrotropin-releasing Hormone(TRH) and Histidyl-proline Diketopiperazine(HPD) in the Maturation of Thermogenesis in Growing Rats

Effects of TRH and its metabolite, histidyl-proline diketopi-perazine (HPD) on the maturation of thermogenesis were examined. Week old Wistar rats were administered 0.04, 0.4 or 4 nmoles of TRH or HPD intrathecally for 7 days. Half of the litters served as saline-treated controls. Body temperature upon cold exposure (5°C, 1-3 hrs) was measured weekly. On the 4th week of age, catecholamines in forebrain, midbrain, cerebellum, brain stem and adrenal glands were measured by HPLC with an EC detector. NADPH-dependent cytochrome C reductase(CCR) and ATPase activities were determined in liver mitochondria and microsomes. TRH showed a dose-dependent thermogenic effect while HPD potentiated hypothermia. This was associated with an elevated or reduced mitochondrial CCR activity in the TRH and HPD groups respectively. No significant differences were noted in either mitochondrial ATPase or microsomal CCR activity. Norepinephrine(NE) and dopamine in midbrain, cerebellum and brain stem were decreased in both groups but adrenal NE was increased in the HPD group. Dose-related changes were not apparent at 4 weeks of age. These results indicate that TRH and HPD exert antagonistic effects on thermogenesis and mitochondrial NADPH-dependent CCR activity and that these changes may be mediated by central and adrenal catecholamine release.

Age-related changes in brain catecholamine responses to a single footshock

—The responses of forebrain and brainstem catecholamine levels to a single footshock were studied in 70-day, one-year, and two-year-old Fischer-344 rats. Brain catecholamine concentrations were assessed 10 minutes after a single 2 second footshock (0, 0.3, or 2.0 mA). In samples taken from non-footshocked rats, only forebrain dopamine concentrations showed a significant age-related decline. However, because the net weights of both the forebrain and the brainstem samples increased significantly with age, the content of forebrain dopamine did not exhibit a significant decline. Both norepinephrine and dopamine levels showed age-related changes in responsiveness to footshock. Norepinephrine concentrations were reduced in both the forebrain and brainstem samples obtained 10 minutes after the high footshock in both the 70-day and one-year-old animals. In two-year-old rats, however, neither forebrain nor brainstem norepinephrine concentrations were altered in response to footshock. Seventy-day-old rats demonstrated significant footshock-induced increases in brainstem dopamine levels, one-year olds showed no appreciable change, and two-year olds demonstrated a non-significant footshock-induced decrease. Thus, both noradrenergic and dopaminergic systems demonstrated age-related changes in their responsiveness to a single brief footshock. These alterations may contribute to the declining ability of the senescent animals to adapt to stressful situations.

Neonatal intraspinal 6-hydroxydopamine, 5,7-dihydroxytryptamine or their combination: Effects on nociception and morphine analgesia

Newborn rats received two injections of intraspinal 6-hydroxydopamine (6-OHDA, 10 μg) or 5,7-dihydroxytryptamine (5,7-DHT, 8 μg preceded by s.c. desmethylimipramine) or a ‘cocktail’ of both neurotoxins. The two injections were separated by 24 h. When assayed in adulthood, the 6-OHDA rats showed a substantial (about 80%) depletion of spinal norepinephrine (NE) but an elevation of brainstem NE. Conversely, the 5,7-DHT rats showed a modest (about 60%) loss of spinal serotonin (5-HT) but an elevation of brainstem 5-HT. Rats receiving combined 6-OHDA plus 5,7-DHT showed rostro-caudal, decreasing gradients of spinal NE and 5-HT depletions, with the largest loss in the lumbar cord. These depletions were much less than those observed after the respective single neurotoxin treatments. Neither the single nor combined neurotoxin treatments altered the tail-flick analgesia induced by morphine (1.0, 3.0 or 7.5 mg/kg s.c.). Basal nociception, however, was altered by the neurotoxins but in a sexually dimorphic manner. The 6-OHDA lowered baseline tail-flick latencies in females while 5,7-DHT elevated latencies in males. Like the 6-OHDA-only rats, the combined 6-OHDA plus 5,7-DHT lowered latencies in females. We conclude that neither spinal NE nor 5-HT are essential to morphine analgesia but do participate in nociception, seemingly in a sexually dimorphic fashion.

REM sleep and depression: common neurobiological control mechanisms.

The author summarizes clinical data showing parallels between REM sleep and depressive phenomena; e.g., patients with endogenous depression show a first REM period that has a shorter than normal latency and a higher density of eye movement. The author discusses evidence for his hypothesis that the following commonalities in neurobiological control systems generate these parallels: 1) brainstem norepinephrine and serotonin systems suppress both REM sleep and depressive phenomena, 2) acetylcholine systems promote both REM and depressive phenomena, and 3) in control of depressive phenomena, as acetylcholine neuronal systems interact and the balance of activity between these two systems, rather than absolute activity levels in either, is the critical factor.