Lack of effects of apomorphine,haloperidol and clozapine on the synthesis and utilization of brain GABA

Summary The synthesis of GABA was studied as the accumulation of GABA following inhibition of the GABA--ketoglutaric acid aminotransferase by-acetylenic GABA (GAG) or-vinyl GABA. The disappearance of GABA was studied by means of inhibition of glutamate decarboxylase by 4-deoxypyridoxine.Systemic administration of the dopamine receptor agonist apomorphine did not change the accumulation or the disappearance of GABA in the substantia nigra and the corpus striatum of the rat. However, a very high dose of apomorphine somewhat increased the GAG-induced GABA accumulation in the corpus striatum. The dopamine receptor antagonists haloperidol and clozapine did not modify the accumulation and disappearance of GABA in the two structures, except for a slight decrease in the GAG-induced GABA accumulation in the substantia nigra.Following an acute hemisection, the neural connections between the substantia nigra and the corpus striatum are interrupted on one side of the brain. Apomorphine did not influence the accumulation or the disappearance of GABA in the substantia nigra and in the corpus striatum on the sectioned side of the brain. These results indicate that the synthesis and the utilization of GABA in the two structures studied are not influenced to any greater extent by changes in dopamine receptor activity.     

Comparison of the effects of dopamine D 1 and D 2 receptor antagonists on rat striatal,limbic and nigral dopamine synthesis and utilisation

Summary The effects of dopamine (DA) antagonists upon DA synthesis and utilisation in the rat striatum, olfactory tubercle and substantia nigra have been studied. The concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the rate of depletion of DA afterin vivo inhibition of tyrosine hydroxylase by H 44/68, and the accumulation of L-DOPA afterin vivo inhibition of 1-aromatic amino acid decarboxylase by NSD 1015 were measured in the study. Haloperidol (0.23mol/kg i. p.), sulpiride (293mol/kg i. p.) and remoxipride (5.6mol/kg i. p.) increased both DA synthesis and utilisation in the striatum and olfactory tubercle. A lower dose of sulpiride (45mol/kg i. p.) increased DA synthesis and utilisation in the olfactory tubercle alone. None of the compounds, at the doses used, affected either DOPAC and HVA concentrations or the rate of utilisation of DA in the substantia nigra. Sulpiride (293mol/kg i. p.) and remoxipride, however, produced a modest rise in nigral DA synthesis. The dopamine D 1-selective antagonist SCH 23390 had only modest effects on striatal, limbic and nigral DA synthesis and utilisation at the doses tested (0.078 and 0.36mol/kg i. p.).     

Effects of GABAergic drugs on the GABA turnover in the substantia nigra and the corpus striatum of the rat

Summary Changes in the endogenous GABA concentration and in GABA turnover following GABA receptor stimulation or blockade were studied in the substantia nigra and the corpus striatum of the rat. The GABA agonists, muscimol, baclofen and THIP decreased the accumulation of GABA following inhibition of GABA--ketoglutaric acid aminotransferase by-acetylenic GABA (GAG) in both structures investigated. Only the effect of muscimol in the substantia nigra was inhibited by the GABA antagonist, bicuculline. Muscimol, baclofen and progabide reduced the disappearance rate of GABA in the substantia nigra following inhibition of the glutamate decarboxylase by 4-deoxypyridoxine. The endogenous GABA concentration was decreased in the corpus striatum following muscimol, THIP or baclofen, probably due to a decreased synthesis of GABA. Smaller effects were seen on the endogenous GABA concentration in the substantia nigra, since both the synthesis and the utilization of GABA were decreased by muscimol and baclofen. Thus, the turnover of brain GABA might be regulated by changes in receptor activity.     

Amphetamine-induced and spontaneous release of dopamine from A9 and A10 cell dendrites: an in vitro electrophysiological study in the mouse

Summary d-Amphetamine (d-AMP) is a potent releaser of dopamine (DA), and its central nervous system stimulant action is mediated primarily through its effect on the substantia nigra and ventral tegmental area dopaminergic neurons (nuclei A9 and A10, respectively). The purpose of the present experiment was to use electrophysiological techniques to examine dendritic release of DA in the in vitro slice preparation, and determine whether: (1) d-AMP inhibits the firing rates of both A9 and A10 cells; (2) the d-AMP-induced inhibition is mediated via the dendritic release of DA; and (3) there isspontaneous dendritic release of DA. Superfusion with d-AMP (2-100 M) produced identical inhibitory dose-response curves for A9 and A10 cells, and a dose of 6.25 M caused more than 50% inhibition in the cell firing rates. The d-AMP-induced inhibition was attenuated by blocking DA synthesis. Either D2 receptor blockade (sulpiride, 1 M), or DA synthesis inhibition (-methylparatyrosine, 50 M) resulted in a marked increase in the firing rates of dopaminergic cells. These data suggest that d-AMP comparably releases DA from both A9 and A10 cell dendrites, that it releases newly-synthesized DA to inhibit cell firing, and that DA is tonically released to regulate cell firing rates via interactions with inhibitory D2 autoreceptors.     

Effect of the normal nerve impulse flow on the synthesis and utilization of GABA in the rat substantia nigra

Summary The concentrations of GABA, glutamate, serine, glutamine, threonine, glycine and taurine in the substantia nigra and in the corpus striatum of the rat were determined electrochemically following condensation with o-phthalaldehyde--mercaptoethanol and reverse-phase, high performance liquid chromatography.After a frontal hemisection at the level of the caudal hypothalamus, the GABA concentration in the substantia nigra on the operated side decreased to about 20 per cent of the normal value in 4 days, in all probability caused by degeneration of the nerve terminals of the striato-nigral GABA neurons. The concentrations of taurine in the substantia nigra and of GABA in the corpus striatum were initially lowered and later elevated following this lesion. The concentration of glutamate in the substantia nigra was lower on the sectioned side and higher on the intact side at 14 days as compared to 4 hours after a hemisection.Following an acute hemisection, the GABA transaminase inhibitor-acetylenic GABA increased the concentration of GABA by 36 % and 79 % in the substantia nigra on the sectioned and intact side, respectively. The glutamate decarboxylase inhibitors 4-deoxypyridoxine and isoniazid lowered the concentration of GABA in the substantia nigra by about 50% on both the sectioned and intact side. The results indicate that the synthesis, but not the utilization of GABA in the substantia nigra is dependent on the normal nerve impulse flow.The concentration of glutamine was changed in directions contrary to that of GABA following a chronic hemisection or treatment with-acetylenic GABA, in agreement with the suggestion that glutamine is a precursor of the GABA transmitter pool.     

Cerebral alterations in a MPTP-mouse model of Parkinson’s disease – an immunocytochemical study

Summary. We investigated the immunohistochemical alterations of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), tyrosine hydroxylase (TH), microtuble-associated protein 2a,b (MAP 2), glial fibrillary acidic protein (GFAP), parvalbumin (PV), and dopamine transporter (DAT) in the striatum and substantia nigra following the application of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. TH-, MAP 2- and DAT-immunoreactive cells were decreased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment, as well as the reduction of the striatal dopamine, DOPAC and HVA content. The number of GFAP-immunoreactive astrocytes increased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment. Striatal nNOS-immunoreactive cells were unchanged in MPTP-treated mice. In the substantia nigra, intense immunoreactivity of nNOS-positive cells increased 5hr after MPTP treatment. Thereafter, the immunoreactivity of nNOS-positive cells decreased gradually from 1 day up to 7 days after MPTP treatment. eNOS-immunopositive cells were unchanged in the striatum and substantia nigra. These results demonstrate that nNOS may play a key role in the development of MPTP neurotoxicity. Our findings also indicate that MPTP can cause the functional damage of interneurons in the substantia nigra, but not in the striatum.Received January 30, 2003; accepted May 14, 2003 Published online August 13, 2003     

Taurine infused intrastriatally elevates,but intranigrally decreases striatal extracellular dopamine concentration in anaesthetised rats

Summary In the present study we infused taurine (50,150 or 450mM, 2l/min for 4h) into the dorsal striatum or into the substantia nigra via microdialysis probe and estimated the extracellular concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the dorsal striatum of anaesthetised rats. Intrastriatal infusion of taurine elevated striatal dopamine at all concentrations studied. At the 450 mM concentration taurine elevated the extracellular dopamine 10-fold, but only in the first 30min sample after starting the taurine infusion. At 50 and 150mM taurine elevated dopamine throughout the 4h infusion maximally up to 3–4-fold the control level. Extracellular DOPAC was increased by 150 and 450mM taurine (up to about 150–160% of the control level), whereas at all three concentrations taurine decreased HVA to about 85% of the control; however, the decrease caused by 450mM taurine was short-lasting. At all three concentrations taurine infused into the substantia nigra decreased the extracellular dopamine in the ipsilateral striatum to about 40–50% of the control, and increased extracellular DOPAC and HVA maximally to about 150% and 170% of the control, respectively. These results show that the effects of taurine on the concentrations of extracellular dopamine and its metabolites depend on its administration site on nigrostriatal dopaminergic neurons. It elevates the extracellular dopamine when given into the striatum, but when given into the cell body region of the nigrostriatal dopaminergic pathway it decreases the extracellular dopamine in the ipsilateral striatum.     

神经节苷脂对帕金森病鼠旋转行为、纹状体多巴胺浓度及黑质病理的影响

目的观察神经节苷脂对帕金森病（Ｐａｒｋｉｎｓｏｎｄｉｓｅａｓｅ，ＰＤ）鼠模型的旋转行为、纹状体多巴胺浓度及黑质病理的影响。方法将６－羟基多巴胺用立体定向法注入大鼠一侧中脑被盖腹侧区制作ＰＤ大鼠模型，并于同侧侧脑室注射混合型神经节苷脂（ａｍｉｘｅｄｇａｎｇｌｉｏｓｉｄｅｐｒｅｐａｒａｔｉｏｎ，ＧＭ），观察ＧＭ对由阿朴吗啡所诱发的旋转行为、受损侧纹状体多巴胺浓度及黑质病理的影响。结果ＧＭ能减轻ＰＤ大鼠模型的旋转行为、使受损侧纹状体多巴胺浓度下降和黑质神经细胞减少。结论ＧＭ可减轻６－羟基多巴胺对黑质多巴胺能神经元的损伤。     

Catecholamine and 5-hydroxytryptamine synthesis and metabolism following intracerebroventricular injection of dibutyryl cyclic AMP

Summary Two to seven days after bilateral implantation of polyethylene tubings into the lateral ventricles rats were injected intracerebroventricularly with dibutyryl cAMP or dibutyryl cGMP. The accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhyrazine HCl, served as a measure of catecholamine and 5-hydroxytryptamine synthesisin vivo.A dose of 100g dibutyryl cAMP per rat but not dibutyryl cGMP increased the accumulation of dopa in all brain regions by 70 to 130%. Both nucleotides stimulated the formation of 5-hydroxytryptophan in the dopamine-rich part of the limbic system and diencephalon and in addition dibutyryl cAMP increased 5-hydroxytryptophan in C. striatum and cerebellum.Dibutyryl cAMP (25–200g per rat) did not change the dopamine levels in the dopamine-rich parts of the brain but decreased the noradrenaline level of the C. striatum in a dose-dependent manner. The same doses of dibutyryl cAMP elevated the 5-hydroxytryptamine level in brain stem and the level of 5-hydroxyindole acetic acid in diencephalon and the limbic system. The disappearance of noradrenaline but not of dopamine after inhibition of catecholamine synthesis with-methyl-p-tyrosine methylester HCl was accelerated in most brain regions.The data are compatible with the view that dibutyryl cAMP stimulates tyrosine and tryptophan hydroxylase directly. In addition, dibutyryl cAMP appears to enhance the utilization of noradrenaline but not that of dopamine. The increased utilization of 5-hydroxytryptamine may be restricted to the diencephalon and the limbic system.     

Sulpiride blocks postsynaptic dopamine receptors in the nucleus accumbens

Summary Intra-accumbens injection of sulpiride, tiapride, and metoclopramide antagonized locomotor hyperactivity induced by intraperitoneal administration of apomorphine in rats and measured over the first five minutes after introducing the animal to an open-field cage. Sulpiride was slightly more potent than tiapride which was more than 10 times more potent than metoclopramide and haloperidol. The threshold dose of sulpiride was as low as 0.001g, bilaterally. Intra-accumbens injection of sulpiride also blocked exploratory hypermotility induced by bilateral intra-accumbens injections of apomorphine and picrotoxin. The threshold dose of sulpiride for blocking these two effects was about 0.01g, bilaterally. Sulpiride was more than 10 times more potent than haloperidol in blocking this apomorphine-induced hypermotility. Haloperidol did not influence the picrotoxin hypermotility.The results obtained indicate strong postsynaptic dopamine antagonist properties of sulpiride, tiapride and metoclopramide.     

Cytoplasmic and axoplasmic density variations in relation to hyperactivity

Summary The density of the cytoplasm and axoplasm of the anterior horn cell in rats was determined by X-ray microradiography. The average density of the cytoplasm of more than 400 cells from control rats was 0.31 g/³, while that of over 600 cells from rats fed IDPN (- iminodipropionitrile) was 0.43 g/³.Hyperactivity developed during the first 5 weeks and was associated with a gradual increase in cytoplasmic density to 0.51 g/³.At 6 weeks there was a drop in density to 0.36 g/³ which coincided with the appearance of axonal balloons having a density of 0.17 g/³.During the 7–12th week on the diet, the cytoplasmic density showed a gradual increase to 0.59 g/³ and the balloons to 0.29 g/³.The volume of the nerve cells remained fairly constant. The density increases were discussed in relation to hypertrophy, dystrophy, and hyperactivity.

---

Zusammenfassung Die Dichte des Cytoplasmas und Axoplasmas der Vorderhornzellen von Ratten wurde durch Röntgenmikroradiographie bestimmt. Die mittlere Dichte des Cytoplasmas von mehr als 400 Zellen der Kontrollratten war 0,31 g/³, während die mittlere Dichte von mehr als 600 Zellen der Ratten, die mit IDPN (- iminodipropionitrile) gefüttert waren, 0,43 g/³ war.Hyperaktivität entwickelte sich während der ersten 5 Wochen und war mit einer progressiven Zunahme der Cytoplasmadichte bis auf 0,51 g/³ verbunden.Nach 6 Wochen sank die Dichte auf 0,36 g/³. Diese Tatsache traf mit dem Auftreten der Axonauftreibungen zusammen, die eine Dichte von 0,17 g/³ hatten.Nach 7–12 Wochen zeigte die Cytoplasmadichte eine progressive Zunahme auf 0,59 g/³ und die der Auftreibungen eine Zunahme auf 0,29 g/³.Das Volumen der Nervenzellen blieb ziemlich konstant.Die möglichen Zusammenhänge zwischen Zunahme der Dichte, Hypertrophie, Dystrophie und Hyperaktivität werden dargestellt.

---

---

Supported by U. S. Public Health Grant NB 1305.     

Effect of tryptophan metabolites on activity of the epileptogenic focus in the frog hippocampus

Summary In frogs with the epileptogenic foci made by injection of penicilline (1000 U in 0.4 mcl) in the primordial hippocampus it was shown that preliminary administration of two kynurenines quinolinic acid (0,1g) and d,l-kynurenine (1g), in the foci region, and their injection in the functioning epileptogenic foci led to a strong increase of the interictal epileptiform discharges and of the electrographic correlates of fits on the EEG. Anthranilic acid (0.1, 1.0 and S.0g) did not influence the activity of epileptogenic foci. Serotonin (1g) and 5-methoxytryptamine (1g) essentially decreased it. Provocating effect of kynurenines on neurons in epileptogenic foci is supposed to play a certain role in pathogenesis of epilepsy.     

Injection of a minuscule dose of FeCl3 within the ventrolateral striatum causes a chronic disturbance of the integrative function within the limbic part of the ventral striatum

Summary The present study shows that low amounts of applied iron have a potent effect on the ventrolateral striatum. This is reflected by an influence on spontaneous night activity, cognitive behaviour during the water maze navigation task, exploratory activity and in response to postsynaptic apomorphine stimulation. Such functional disturbances could be observed up to months after a single application of either 0.3 g or 1.5 g FeCl₃. The low dose of iron stimulates while 1.5 g inhibits the spontaneous dopaminedependent locomotor night and explorative activity. The low concentration of ionic iron injected intrastriatally also increases lipid peroxidation in striatal and hippocampal tissues. These results suggest that the functional integrity of the ventral striatum and the regulation of the iron metabolism are critical for the sensorimotor performance.     

The effect of reserpine treatment in vivo upon L-dopa and amphetamine evoked dopamine and DOPAC efflux in vitro from the corpus striatum of male rats

Summary In the present experiment we tested the effects of L-DOPA and amphetamine upon dopamine and DOPAC efflux in vitro from superfused corpus striatal tissue fragments of male rats who had been pretreated with reserpine. Male rats were treated with reserpine (5mg/kg) or its vehicle at 24 hours prior to sacrifice and superfusion of the corpus striatum. Two different modes of L-DOPA (5 M) and amphetamine (10 M) stimulation, a brief 10-minute and a continuous 60-minute infusion, were tested for their ability to evoke striatal dopamine and DOPAC efflux. Depletion of monoamine storage capacity as achieved with reserpine significantly reduced the amount of basal dopamine and DOPAC released from superfused striatal tissue fragments of male rats. Although basal release rates were significantly reduced, the amount of dopamine and DOPAC released in response to in vitro L-DOPA infusions (10 or 60 minute infusions) was equivalent between reserpine and vehicle treated animals. In contrast, amphetamine stimulated DA release was significantly reduced in male rats treated with reserpine. For both L-DOPA and amphetamine, significantly greater amounts of dopamine were obtained with the 60-versus 10-minute infusion modes. These results demonstrate that the capacity for L-DOPA, but not amphetamine, to evoke dopamine efflux is unaltered under conditions when monoamine storage ability is diminished.     

Human brain phenolsulfotransferase. Regional distribution in Parkinson's disease

Summary Brain phenolsulfotransferase (PST) in 105.000×g supernatant fractions prepared from post mortem human brain catalyzes the sulfate conjugation of dopamine (DA). Using 50 M DA, the PST activity was linear up to one hour. The KM value for DA was 3.1 M. Higher concentrations of DA from 25 bM up caused inhibition of PST activity. Assessment of regional distribution in normal brain using 20 M DA concentration revealed the highest PST activites in temporal and frontal cortex. About ten times lower activities were measured in parietal and occipital lobe, amygdala, hypothalamus, and hippocampus, whereas the nucleus accumbens, nucleus basalis of Meynert, caudate nucleus, and substantia nigra showed the lowest activities (about 1% of those in frontal and parietal cortex). In the brains of subjects with Parkinson's disease (PD) treated with levodopa, a significant reduction of PST activities was observed in hypothalamus, frontal and temporal cortex, amygdaloid nucleus, occipital and parietal cortex (between 20 and 38.8% of controls). Depletion of PST activity was less severe in hippocampus (46% of controls), nucleus accumbens, putamen, and substantia nigra (67 and 72% of controls, respectively). No changes were observed in the nucleus basalis of Meynert, while PST activity was increased in the caudate nucleus (174 to 203% of controls). The presented data indicate that on PD brain the PST activity is reduced in areas of the cerebral isocortex and limbic system, while in the basal ganglia it is either mildly reduced (putamen) or increased (caudate nucleus). Selective changes of PST activity in PD brain may indicate an important function of this enzyme in the metabolism and/or storage of DA under pathological conditions.     

Potentiation of yawning responses to the dopamine receptor agonists B-HT 920 and SND 919 by pindolol in the rat

Summary Subcutaneous injection of B-HT 920, a dopamine D₂-receptor agonist, in doses ranging from 5 to 100g/kg, induced yawning behavior in rats. Yawning was also elicited by low doses (25–500 g/kg sc) of SND 919, a newly synthesized dopamine receptor agonist. The yawning evoked by B-HT 920 or SND 919 was increased by the -adrenoceptor antagonist pindolol (20mg/kg ip) which alone did not induce yawning. Stereotyped behavior did not appear after B-HT 920 or SND 919 given alone or in combination with pindolol. The results suggest that SND 919 as well as B-HT 920 has stimulatory activity at dopamine D₂-receptors, and that pindolol may exert its enhancement of the yawning response to dopamine receptor agonists via blockade of -adrenoceptors.     

Thioctic acid does not restore glutathione levels or protect against the potentiation of 6-hydroxydopamine toxicity induced by glutathione depletion in rat brain

Summary Decreased reduced glutathione (GSH) levels are an early marker of nigral cell death in Parkinson's disease. Depletion of rat brain GSH by intracerebroventricular administration of buthionine sulphoximine (BSO) potentiates the toxicity of 6-hydroxydopamine (6-OHDA) to the nigrostriatal pathway. We have investigated whether thioctic acid can replenish brain GSH levels following BSO-induced depletion and/or prevent 6-OHDA induced toxicity.Administration of BSO (2 × 1.6 mg ICV) to rats depleted striatal GSH levels by upto 75%. BSO treatment potentiated 6-OHDA (75 g ICV) toxicity as judged by striatal dopamine content and the number of tyrosine hydroxylase immunoreactive cells in substantia nigra. Repeated treatment with thioctic acid (50 or 100mg/kg i.p.) over 48h had no effect on the 6-OHDA induced loss of dopamine in striatum or nigral tyrosine hydroxylase positive cells in substantia nigra. Also thioctic acid treatment did not reverse the BSO induced depletion of GSH or prevent the potentiation of 6-OHDA neurotoxicity produced by BSO.Thioctic acid (50mg or 100mg/kg i.p.) alone or in combination with BSO did not alter striatal dopamine levels but increased dopamine turnover. Striatal 5-HT content was not altered by thioctic acid but 5-HIAA levels were increased.Under conditions of inhibition of GSH synthesis, thioctic acid does not replenish brain GSH levels or protect against 6-OHDA toxicity. At least in this model of Parkinson's disease, thioctic acid does not appear to have a neuroprotective effect.     

Die spektralphotometrische Analyse des Liquor cerebrospinalis im UV-Licht

Zusammenfassung Die spektralphotometrische Bestimmung der Absorptionskurve des natürlichen Liquors im UV-Licht gestattet in exakt reproduzierbarer Weise normale und pathologische Liquores zu unterscheiden. Dies ist namentlich bei Verlaufskontrollen von Bedeutung. Ein konstantes Absorptionsmaximum (A) findet sich im kurzwelligen Bereich bis 240 m und ist zur quantitativen Eiweißbestimmung mit einer für die klinischen Bedürfnisse hinreichenden Genauigkeit geeignet. Eine von den quantitativen Eiweißwerten unabhängige Absorptionsbande ( A) hat ihr Maximum bei allen normalen und den meisten pathologischen Liquors bei 266 m Eine Verschiebung nach 275 m kommt vereinzelt bei pathologischen Liquores vor.Eine starke A mit einem Durchlaßgrad von weniger als 30% spricht auch bei im übrigen normalen Liquorwerten für pathologische Veränderungen.Das mittels Perchlorsäure gefällte Liquoreiweiß zeigt in alkalischer Lösung ein dem Grade nach von dem Eiweißgehalt abhängiges Absorptionsmaximum bei 215 m und eine flache Absorptionsbande zwischen 275–285 m.     

Selective subregional dopamine depletions in the rat caudate-putamen following nigrostriatal lesions.

Previous work has demonstrated a complex neurochemical and neuroanatomical heterogeneity of the striatum in normal brains. The present research investigated whether the heterogeneous distribution of dopamine would be altered following unilateral injections of the neurotoxin 6-hydroxydopamine into the substantia nigra of the rat. Four weeks following injection, the nucleus accumbens and subregions of the caudate-putamen and substantia nigra were dissected and analyzed by HPLC with electrochemical detection for dopamine, 5-hydroxytryptamine, and their respective metabolites. Levels of dopamine and its metabolites in the anterodorsolateral caudate-putamen were depleted more than medial, posterior, and ventral, striatal areas in partially lesioned animals (less than 90% dopamine depletion). This resulted in an alteration of striatal heterogeneity such that a mediolateral gradient of dopamine tissue content was now superimposed on the normal rostrocaudal gradient observed in controls. Paralleling these findings, dopamine was more depleted in the lateral, as opposed to the medial, substantia nigra. These results indicate that the nigrostriatal dopamine system degenerates in a heterogeneous fashion following 6-hydroxydopamine administration. It is speculated that the differential loss of dopamine neurons observed in the nigra of Parkinson's patients may be due to a differential sensitivity to toxins within the nigra.     

Acute effects of histamine on plasma prolactin and luteinizing hormone levels in male rats

Summary Histamine injected into the 3rd ventricle of normal male rats at doses of 5–60g (free base) caused a marked release of prolactin. Responses were prevented by the antihistamine chlorpheniramine but not by atropine, methysergide or phenoxybenzamine. It thus seems that effects of histamine on prolactin are specific and not mediated by other neurotransmitters. Plasma LH remained normal after injection of low doses but it was decreased after high doses.The results obtained indicate a facilitatory role of histamine on prolactin release.