Both thermal and nociceptive afferents influence the unit activity of the neurons in the corpus striatum

Summary Both thermal and nociceptive stimulation in the periphery were shown to influence the neuronal activity recorded in the striatal area. Both the thermal and nociceptive sensitivity of the striatal neurons were closely related.The authors are grateful to the Alexander von Humboldt-Stiftung (Bad Godesberg, Bonn, Federal Republic of Germany) for donations of the necessary equipment for the present study. The research reported here was supported by grants from the National Science Council (Taipei, Taiwan, Republic of China)     

Role played in man by myelinated fibers of different diameters for the evocation of a nociceptive flex reflex and the accompanying pain sensation]

Using simultaneous recordings we have made in Man a comparative study of: the sural nerve afferent volley, the nociceptive flexor reflex of a muscle of the lower limb and the associated painful sensation. Two types of stimulations were used, a single short duration electric stimulus, and a train of electric shocks (100/sec). With a single stimulus, the nociceptive flexor reflex and the painful sensation develop only when A delta fibers are recruited. On the other hand, when the stimulations are given by trains the nociceptive flexor reflex and the painful sensation can develop with a stimulus sub-liminar to the threshold of A delta fibers, when A alpha fibers are recruited. When the stimulus activate both A alpha and A delta fibers, the flexion reflex and the pain disappear when a selective blockade of the A delta group is exerted by means of Lidocain.     

Central terminals of capsaicin-sensitive primary afferent make synaptic contacts with neuronal soma in the mouse substantia gelatinosa

Degeneration of primary afferent central terminals (C-terminals) that contact neuronal soma in the substantia gelatinosa of the spinal dorsal horn was examined by electron microscopy 2 h after s.c. injection of capsaicin into newborn and adult mice. The C-terminals were small, dark, sinuous or slender terminals with clear synaptic vesicles in the early postnatal period. They are thought to develop into scalloped CI-terminals, surrounded by dendrites and a few axonal endings, forming synaptic glomeruli. The same type of nonglomerular terminals making presynaptic contacts with neuronal soma showed degeneration in both the newborn and adult animals, and were identified as capsaicin-sensitive CI-terminals. This finding suggests that capsaicin-sensitive C-fibers have a modulatory role on their own nociceptive input besides functioning in nociceptive transmission in the substantia gelatinosa.     

Effect of benzatropine on the O-methylation of striatal dopamine]

After treatment by nialamid, benztropine administered to Rats produced an increase in the level of 3-O-methyldopamine in the corpus striatum. It produced a slight increase in the level of striatal dopamine and no change in the level of norepinephrine. The monoamine oxydase and catechol-O-methyltransferase activities of remaining brain showed no variations by benztropine. The results suggest the possible involvement of striatal dopamine and its extraneuronally catabolism in the antiparkinsonian effect of benztropine.     

Dopamine synthesis in rat striatum: mobilization of tyrosine from non-dopaminergic cells

Unilateral nigrostriatal lesions in rats that almost totally depleted striatal dopamine had no effect on striatal levels of dopamine's precursor, tyrosine, nor on those of leucine. Since prolonged electrical stimulation of the slices markedly depletes them of tyrosine (1,2) we conclude that tyrosine can be mobilized from non-dopaminergic striatal cells to augment dopamine release.     

Effects of L-aspartic acid,L-asparagine and/or L-asparaginase on forced swimming-induced immobility,analgesia, and decrease in rectal temperature in rats

Summary The effect of L-aspartic acid, L-asparagine and/or L-asparaginase were compared with those of imipramine on immobility, number of defecations, increase of nociceptive threshold, and hypothermia, induced by forced swimming in rats. L-Aspartic acid was found to be as effective as imipramine in reducing the effects of forced swimming, presumable by normalizing the decreased level of endogenous L-aspartic acid, due to the inhibition of L-asparaginase activity and/or by stimulated the inhibited enzyme. The other treatments antagonized the immobility, but not the increased number of defecations. All compounds abolished the elevation of nociceptive threshold and hypothermia.     

Dopamine synthesis in rat striatum: Mobilization of tyrosine from non-dopaminergic cells

Summary Unilateral nigrostriatal lesions in rats that almost totally depleted striatal dopamine had no effect on striatal levels of dopamine's precursor, tyrosine, nor on those of leucine. Since prolonged electrical stimulation of the slices markedly depletes them of tyrosine (1, 2) we conclude that tyrosine can be mobilized from non-dopaminergic striatal cells to augment dopamine release.     

Human neuropharmacological findings with oxapadol (MD 720111), a new non-narcotic analgesic

Summary The effects of oxapadol, a new non-narcotic analgesic, were tested in man using the electrically-induced nociceptive flexion reflex in the flexor muscles of the lower limb as an index of pain. The drug caused a significant increase in the threshold of the reflex whereas no change was noted with placebo.     

Antidromic latency variations of nigral compacta neurones

Summary Variations in the antidromic latency of substantia nigra compacta neurones were commonly observed following striatal stimulation. These results provide electrophysiological evidence for a branched unmyelinated nigrostriatal pathway and demonstrate that the antidromic criterion of constant latency is not valid for this type of pathway.     

Massive striatal dopamine release in acute cerebral ischemia in rats

Summary Extracellular dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and cerebral blood flow were simultaneously determined using in vivo brain dialysis and a hydrogen clearance method in the striatum of spontaneously hypertensive rats during ischemia and after recirculation. Massive striatal dopamine release was demonstrated in acutely induced ischemic brain.     

Behavior modifications induced by unilateral administration of picrotoxin into rat substantia nigra]

Intranigral injection of picrotoxin in Rats induced contralateral rotation and stereotyped behaviour. These responses were significantly altered following neuroleptic treatment (haloperiod, pimozide) or ipsilateral striatal electrolytic destruction. The present results provide behavioural evidence for gamma-aminobutyric acid-mediated inhibition of the dopaminergic nigrostriatal pathway.     

Accumulation of 3H-dopamine by synaptic vesicles from rat striatum in an impermeant medium

The accumulation of 3H-dopamine by synaptic vesicles from rat striatum was significantly stabilized in a membrane impermeant medium. The characteristics of dopamine accumulation by striatal vesicles were quite similar to those reported for dopamine accumulation by a whole brain vesicle preparation in the same medium, and were significantly different from the characteristics previously reported for vesicular accumulation of norepinephrine.     

In vivo continuous electrochemical determination of dopamine release in rat neostriatum]

Polarographic micro-electrodes (carbon fiber, o. d. 8 micron) implanted in the Rat caudate nucleus, allowed a practically continuous in vivo monitoring (one measurement every 5 sec.) of the extra-cellular concentration of dopamine released by striatal dopaminergic terminals. Administration of amphetamine produced a reproducible increase of the oxidation current. This effect was suppressed after the selective degeneration of the striatal dopaminergic terminals following the injection of 6-OHDA into the substantia nigra or after inhibition of the synthesis of the amine by alpha methyl-p-tyrosin. After 5 hrs. this drug produced a 70% decrease of the oxidation current.     

Multiple daily amphetamine administration decreases both [3H]agoinst and [3]antagonist dopamine receptor binding

Summary Multiple daily amphetamine injections in rats decreased both [³H]agonist as well as [³H]antagonist striatal dopamine receptor binding. Concurrently, these animals exhibited a decrease in striatal dopamine concentration and, paradoxically, an enhancement of behavioral responsivity.This study was supported by PHS grant MH32990 to I.C. and DA0156805 to D.S.I. Creese and D. Segal are the recipients of the RSDA grants MH00316-01 and RSDA MH70183-08, respectively.     

Piroxicam-induced analgesia: evidence for a central component which is not opioid mediated.

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p < 0.05) and 50% (p < 0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.     

Piroxicam-induced analgesia: Evidence for a central component which is not opioid mediated

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p<0.05) and 50% (p<0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.     

Two novel prolactin release-inhibiting 8α-amino-ergolines

Summary Prolactin secretion inhibition and changes in striatal dopamine metabolism in rats were compared after the administration of 8a-amino-ergoline CH 29-717 and 2 derivates. CQ 32-084 was similar to but less potent than CH 29-717. while 32-085, the 1-methyl derivative, showed delayed dopaminomimetic effects.     

Melatonin receptors limit dopamine reuptake by regulating dopamine transporter cell-surface exposure

Melatonin, a neuro-hormone released by the pineal gland, has multiple effects in the central nervous system including the regulation of dopamine (DA) levels, but how melatonin accomplishes this task is not clear. Here, we show that melatonin MT₁ and MT₂ receptors co-immunoprecipitate with the DA transporter (DAT) in mouse striatal synaptosomes. Increased DA re-uptake and decreased amphetamine-induced locomotor activity were observed in the striatum of mice with targeted deletion of MT₁ or MT₂ receptors. In vitro experiments confirmed the interactions and recapitulated the inhibitory effect of melatonin receptors on DA re-uptake. Melatonin receptors retained DAT in the endoplasmic reticulum in its immature non-glycosylated form. In conclusion, we reveal one of the first molecular complexes between G protein-coupled receptors (MT₁ and MT₂) and transporters (DAT) in which melatonin receptors regulate the availability of DAT at the plasma membrane, thus limiting the striatal DA re-uptake capacity in mice.     

交会对接载人组合体热管理技术研究

组合体热管理是优化交会对接载人组合体热控设计,实现长期载人热环境控制的重要手段.在对目标飞行器和载人飞船组合体热特性分析的基础上,提出了以舱段间通风为技术手段的交会对接载人组合体热管理方案,并结合热平衡试验数据,建立了组合体热管理系统分析模型.仿真结果、地面热平衡试验数据和在轨飞行数据表明,组合体密封舱内空气流速分布满足要求,温度在19~26°C可调,空气相对湿度在30%~70%范围内,验证了交会对接载人组合体热管理设计的正确性.最后对空间站等复杂组合体热管理设计提出了建议.     

Interaction of CDP-choline with synaptosomal transport of biogenic amines and their precursors in vitro and in vivo in the rat corpus striatum.

Added to a striatal synaptosomal homogenate of rat brain, CDP-choline 10(-4) M inhibits the uptake of norepinephrine (NE), dopamine (DA) and serotonin (5 HT) in a competitive fashion and enhances the uptake of tyrosine and tryptophan; administered to animals, CDP-choline (50 mg/kg/l h/i.v.) inhibits only the in vitro uptake of DA but enhances the uptake of precursors.