Nonparallel changes in brain monoamines of pyridoxine-deficient growing rats

Summary The effects of a large number of neurotropic drugs have been attributed to changes in the metabolism of 5-hydroxytryptamine. The aromatic amino acid decarboxylase considered to decarboxylate both dihydroxyphenylalanine and 5-hydroxytryptophan requires pyridoxal phosphate as coenzyme. Thus, in pyridoxine deficiency one would expect a decrease of serotonin as well as the catecholamines of the brain. In the present study we have found a very significant decrease in brain serotonin of the pyridoxine-deficient growing rat. However, the brain levels of norepinephrine and dopamine were not altered. This decrease in serotonin does not result from a decrease either in the brain level of tryptophan or the activity of tryptophan hydroxylase. Increased degradation of serotonin measured by the levels of its metabolite, 5-hydroxyindoleacetic acid is also excluded, thus suggesting the possibility that the decarboxylation of 5-hydroxytryptophan is decreased in pyridoxine deficiency.     

Monoamines (norepinephrine,dopamine, serotonin) in the rat medial vestibular nucleus: endogenous levels and turnover

Summary Monoamine (norepinephrine, dopamine, serotonin) and metabolite endogenous levels were determined in the rat medial vestibular nucleus (MVN) using HPLC with electrochemical detection. As a comparison, the locus cruleus (LC) and dorsal raphe nucleus (RD) which contain the cell bodies of MVN noradrenergic and serotoninergic neurons respectively were also analyzed. Norepinephrine (NE) and serotonin (5-HT) basal levels of MVN were high (33.8 and 39.2pmol/mg protein respectively) but lesser than in LC or RD. Great amounts of MHPG and 5-HIAA were also present in the MVN. The turnover of NE assessed both from the ratio MHPG/NE and by the decrease in the NE content after treatment with -methylparatyrosine was faster in the MVN (half-life 1.5h) than in LC (half-life 3.6h). On the other hand, the ratio 5-HIAA/5-HT was lower in the MVN (0.58) than in the RD (0.85) indicating a smaller 5-HT turnover in the MVN. In addition, like LC and RD, the MVN contained meaningful amounts of dopamine (DA) and DOPAC. The high ratio DA/NE (0.27) suggests the presence of non precursor specific dopaminergic pools. However, individualized dopaminergic neurons have not yet been demonstrated. The data are discussed in line with the possible neurotransmitter function of monoamines in the MVN.     

The effect of taurine on motor behaviour,body temperature and monoamine metabolism in rat brain

Summary Taurine, a putative inhibitory neurotransmitter, was injected in various doses intracerebroventricularly to conscious rats via pre-implanted polythene cannulas. The formation of DOPA and 5-hydroxytryptophan (5-HTP) in various brain regions was investigated by measuring the accumulation of these monoamine precursors induced within 30 min by the intraperitoneal injection of 3-hydroxybenzyl hydrazine HCl (NSD 1015, 100 mg/kg), an inhibitor of the aromatic L-amino acid decarboxylase readily penetrating into the brain. DIPA formation, but not 5-HTP formation was significantly enhanced by taurine in dose-related manner in all brain regions studied, indicating an increased synthesis of both dopamine and noradrenaline. Dopamine depletion induced by -methyltyrosine was significantly retarded by taurine, whereas noradrenaline depletion tended to be enhanced. Endogenous levels of dopamine were increased, whereas the following brain constituents were unchanged: tyrosine, tryptophan, noradrenaline, 5-HT and 5-hydroxyindoleacetic acid. In the exoeriments with NSD 1015, a dose-related decrease in rectal temperature and in motility was observed after taurine treatment, as compared to treatment with the decarboxylase inhibotor alone. Systemic parenteral administration of taurine caused no significant changes in brain monoamines, body temperature or behaviour but decreased the heart noradrenaline levels. The data indicate that taurine, which apparently has to be given intracerebroventricularly in order to reach the brain in sufficient amounts, causes inhibition of firing in central dopamine neurons but has the opposite effect on noradrenaline neurons, perhaps also peripherally, whereas 5-HT neurons appear to be unaffected. In addition, taurine appears to interfere with motor behaviour and temperature regulation, possibly via effects on catecholaminergic systems.     

Importance of the Locus coeruleus and involvement of α-adrenergic receptors in the post-decapitation reflex in the rat

The latency, duration, hindlimb kick frequency, and total activity components of the post-decapitation reflex (PDR) were measured in the rat using a movement-sensitive transducer. Reduction of brain and spinal cord norepinephrine (NE) caused by neonatal administration of 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine, which also reduced brain serotonin, decreased all components of the PDR. Depletion of serotonin or dopamine alone reduced the vigor of the reflex, suggesting that these pathways can influence the PDR but are not essential for the response. Lesions of neurons in the Locus coeruleus, made electrolytically or with 6-OHDA, decreased the intensity of the PDR, with the 6-OHDA-induced lesion being more effective. Depletion of forebrain NE terminals with 6-OHDA did not alter the PDR, consistent with a critical involvement of spinal noradrenergic fibers. The PDR was also decreased by phentolamine and prazosin, but not by propanolol, suggesting an involvement of -adrenergic receptors in the response. This hypothesis was further supported by the finding that the efficacy of a variety of drugs (such as tricyclic antidepressants, phenothiazines, and antihypertensive compounds) for blocking the reflex was apparently related to their affinity for -adrenergic receptors. Thus, the PDR is dependent on noradrenergic fibers in the spinal cord and may provide a simple screen for drugs with suspected -adrenergic blocking properties or for agents that disrupt the function of central noradrenergic fibers.Bruce A. Pappas was a visiting Professor on sabbatical leave from the Department of Psychology, Carleton University, Ottawa, Canada K1S 5B6     

Naloxone effects on β-endorphin,cortisol, prolactin,growth hormone,HVA and MHPG in plasma of normal volunteers

8 mg of naloxone were administered IV to 14 normal volunteers in a placebo-controlled, double-blind experiment. Plasma levels of -endorphin, cortisol, prolactin, growth hormone, HVA and MHPG were determined before and 45 min after administration. Naloxone elicited significant increases in cortisol and MHPG but did not change plasma levels of the other compounds. In an additional experiment on two subjects, 20 mg of naloxone caused elevations of -endorphin as well as of cortisol. This parallel increase indicates that the linkage between the secretion of -endorphin and ACTH/cortisol may be dose-dependent. The increase in MHPG is in agreement with the hypothesized association of noradrenergic hyperactivity and opiate withdrawal.     

Prolongation of the ejaculation latency in the male rat by thioridazine and chlorimipramine

Thioridazine (3 mg/kg) and chlorimipramine (1.5–6.0 mg/kg) prolonged the ejaculation latency and increased the number of mounts but did not change the number of intromissions preceding ejaculation. Blockade of peripheral and central noradrenaline receptors by phentolamine and phenoxybenzamine respectively resulted in a suppression of all aspects of the sexual behavior with increasing doses. dl-5-HTP (25–100 mg/kg) in combination with an inhibitor of peripheral 5-HTP decarboxylase (benserazide, 25 mg/kg) produced, like chlorimipramine and thioridazine, a prolongation of ejaculation latency and an increase in the number of mounts preceding ejaculation. Selective inhibition of 5-HT reuptake however, by zimelidine (0–20 mg/kg) or alaproclate (0–20 mg/kg) did not affect the mating behavior. At higher doses of these drugs some animals failed to initiate sexual activities. There was an increase in the postejaculatory interval but no change in the ejaculatory latency.It is concluded that the prolonged ejaculation latencies observed following treatment with thioridazine or chlorimipramine is not due to a blockade of central or peripheral adrenergic -receptors.     

Effects of Ethyl Alcohol Administration to THA Rat Dams During Their Gestation Period on Learning Behavior and on Levels of Monoamines and Metabolites in the Brain of Pups after Birth

Children born from chronic alcoholic mothers have shown behavioral teratogenic effects more frequently than morphological malformations. To investigate the possible mechanisms and evaluate maternal alcohol dosage levels to induce behavioral dysfunctions, we gave pregnant Tokai High Avoider (THA) rats 0, 5,10, and 20% ethanol (EtOH) as drinking water during the gestation period. We evaluated the brain function of pups born of alcohol-administered dams. Sidman avoidance behavior test and the levels of monoamines (nor-adrenalin, dopamine, and serotonin) and metabolites (3,4-dihydroxy-phenyl acetic acid, homovanillic acid, and 5-hydroxyindole acetic acid) in whole brain were examined for neurobehavioral and neurochemical effects. EtOH-exposed THA offsprings showed high pre-and postnatal mortality, growth deficits, and brain weight reductions. Compared with the results of the same conditioning experiment using Wistar rats, the THA rat may have higher susceptibility to the effects of in utero EtOH exposure than Wistar rats. EtOH-exposed THA pups exhibited deficits in avoidance operant learning that were not shown in Wistar rats. We also observed the increased levels of all monoamines that were assumed to be related with the deficit of learning, the decreased levels of 3,4-dihydroxyphenyl acetic acid and homovanillic acid, and the unchanged levels of 5-hydroxyindole acetic acid in pups from dams administered 10 and 20% EtOH. However, contrary alteration of monoamines and their metabolites were shown in pups from 5% EtOH-administered dams.     

氟对大鼠子代脑单胺类神经介质的影响

Ｗｉｓｔａｒ大鼠自查到阴栓起，分别自由饮用０．６ｍｇ／Ｌ（对照组）、１ｍｇ／Ｌ、５ｍｇ／Ｌ、２５ｍｇ／Ｌ含氟水，其仔鼠饮用同浓度含氟水至９０ｄ，观察胚胎期及生长发育期接触氟对仔鼠大脑功能的影响。采用高压液相色谱－电化学法对大脑单胺类神经介质测定结果显示，除多巴胺的代谢产物之一－３，４－二羟乙酸（ＤＯＰＡＣ）的含量在高剂量组显著降低外，去甲肾上腺素（ＮＥ）、多巴胺（ＤＡ）、高香草酸（ＨＶＡ）、５－羟色胺（５－ＨＴ）和５－羟吲哚乙酸（５－ＨＩＡＡ）的含量与对照组比较均无显著差异，表明氟可抑制ＤＡ的代谢转化，对单胺氧化酶（ＭＡＯ）的活性有一定的抑制作用。提示氟对仔鼠的大脑功能有一定的不良影响。     

Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice

The taiep rat is a myelin mutant in which immobility episodes (IEs) can be induced in adult males by gripping. EEG recordings during gripping-induced IEs show a rapid eye movement (REM) sleep-like pattern, similar to that reported for narcolepsy-cataplexy suggesting that IEs represent a disorder of REM-sleep. An alpha(2) adrenoceptor agonist increases gripping-induced IEs, whereas alpha(2) antagonists decrease these. We have studied the effect of prazosin on IEs and the levels of alpha(1) adrenoceptors were evaluated in cerebro-cortical homogenates of taiep and control rats. Systemic administration of prazosin results in a significant increase in both the frequency and duration of gripping-induced IEs. Our results show that cerebro-cortical tissue is not an adequate candidate for the expression of cataplexy-like symptoms, but prazosin, an alpha(1) antagonist, is a potent inducer of gripping-induced immobility episodes in taiep rats.     

Inhibition of the responses of cat dorsal horn neurons to noxious skin heating by stimulation in medial or lateral medullary reticular formation

Summary Responses of single lumbar dorsal horn units to noxious radiant heating (50° C, 10 s) of glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% nitrous oxide. The heat-evoked responses of 37/40 units were reduced during electrical stimulation (100 ms trains, 100 Hz, 3/s, 25–600 A) in the medullary nucleus raphe magnus (NRM) and/or in laterally adjacent regions of the medullary reticular formation (MRF). Inhibition was elicited by stimulation in widespread areas of the medulla, but with greatest efficacy at ventrolateral sites. The magnitude of inhibition increased with graded increases in medullary stimulation intensity. Mean current intensities at threshold for inhibition or to produce 50% inhibition were higher for NRM than for MRF sites. Units' responses to graded noxious heat stimuli increased linearly from threshold (42–43° C) to 52° C. During NRM (5 units) or ipsilateral MRF stimulation (7 units), responses were inhibited such that the mean temperature-response functions were shifted toward higher temperatures with increased thresholds (1.5° and 1° C, respectively) and reduced slopes (to 60% of control). Contralateral MRF stimulation had a similar effect in 4 units. Inhibitory effects of NRM and MRF stimulation were reduced (by >25%) or abolished in 4/6 and 5/12 units, respectively, following systemic administration of the serotonin antagonist methysergide. Inhibitory effects from NRM, ipsi- and contralateral MRF were reduced or abolished in 2/9, 4/8 and 6/9 cases, respectively, following systemic administration of the noradrenergic antagonist phentolamine. These results confirm and extend previous studies of medullospinal inhibition and the role of monoamines, and are discussed in terms of analgesic mechanisms.