Neurochemical correlate of a spatial preference in rats

Spatial (left or right) preferences were determined for rats given foot shock in a T-maze. The animals were killed, and left and right striata were assayed separately for dopamine and left and right teldiencephalic regions were assayed for norepinephrine. Dopamine content was significantly higher (by 12 percent) in the striata contralateral to rats' side preferences than in the ipsilateral striata; there was no such difference for teldiencephalic norepinephrine. The small asymmetry in striatal dopamine content is not due to any learning- or stress-related change induced by the testing procedure but is probably inherent in normal rats. Some spatial behavior appears to be the manifestation of a normal and specific difference in the activity of left and right nigrostriatal systems.     

Is reserpine tranquilization linked to change in brain serotonin or brain norepinephrine?

Reserpine, when administered to animals stressed by exposure to cold, does not induce sedation or appreciably lower brain serotonin, but markedly lowers brain norepinephrine. Reserpine in cold-exposed hypophysectomized rats elicits sedation and releases both amines equally. The results support the view that the tranquilizing action of reserpine is not related to brain norepinephrine loss but rather to change in the level of brain serotonin.     

Pituitary-adrenal influences on fear responding

In a passive avoidance situation, hypophysectomized male rats show less fear than normal rats, whereas adrenalectomized rats show greater fear than normals. These results probably occur because hypophysectomized rats lack adrenocorticotrophic hormone, which increases arousal or emotionality, whereas adrenalectomized animals lack certain adrenal steroids, which inhibit excitatory effects. The results indicate that adrenocorticotrophic hormone and certain adrenal steroids have opposite effects in regulating fear-motivated behavior.     

Dopaminergic terminals in the rat cortex

The destruction of ascending noradreniergic pathways by bilateral microinjections of 6-hydroxydopamnine made laterally to the pedunculus cerebellaris superior completely abolished the in vitro synthesis of [(3)H]norepinephrine from L-[(3)H]tyrosine in slices and in synaptosomes of the rat cortex. However, normal [(3)H]dopamine synthesis could still be observed in both cortical preparations from animals with lesions. These results provide the first biochemical support for the existence of dopaminergic terminals independent of noradrenergic terminals in the rat cortex.     

Perinatal undernutrition: accumulation of catecholamines in rat brain

Brains of rats undernourished from midgestation and killed at weaning contained 25 percent less norepinephrine than brains of adequately fed littermates. Perinatal undernutrition also suppressed the accumulation of brain dopamine. Paradoxically, the activity of tyrosine hydroxylase, the enzyme thought to be rate-limiting in catecholamine biosynthesis, was significantly increased in brains from undernourished animals.     

NOREPINEPHRINE AND 3,4DIHYDROXYPHENETHYLAMINE TURNOVER IN GUINEA PIG BRAIN IN VIVO

By administering C(14)-la-beled tyrosine or H(3)-labeled 3,4-dihy-droxyphenylalanine to guinea pigs it has been possible to achieve sufficient labeling of the norepinephrine and dopamine in the brain to permit measurement of their turnover rates. The half-life of brain dopamine was about 2.5 hours. The half-life of norepinephrine was about 4 hours, suggesting a rate of synthesis of at least 0.03 to 0.04, microg/g per hr or 2.4 microg/day for the whole guinea pig brain.     

Luteinizing hormone-releasing factor potentiates lordosis behavior in hypophysectomized ovariectomized female rats

Subcutaneous injection of luteinizing hormone-releasing factor (LRF) in estrogen-primed hypophysectomized, ovariectomized female rats facilitates the appearance of the lordosis response. The LRF effect on lordosis was seen 90, 180, and 360 minutes after injection. This effect could help to synchronize the female's mating behavior with the ovulatory discharge of luteinizing hormone.     

Deficits in feeding behavior after intraventricular injection of 6-hydroxydopamine in rats

Intraventricular injections of 6-hydroxydopamine produced 95 percent depletion of telencephalic norepinephrine and 62 percent depletion of striatal dopamine in rats. Treated rats maintained body weight at subnormal levels and failed to increase food intake in response to a short-term decrease in glucose utilization. After treatment with the monoamine oxidase inhibitor pargyline, 6-hydroxydopamine produced no further norepinephrine depletion but increased the dopamnine depletion to 95 percent and produced complete aphagia. These effects are comparable to events that follow bilateral electrolytic lesions of the lateral hypothalanmus.     

Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate

Whether growth hormone stimulates longitudinal bone growth by a direct effect at the site of the growth plate or indirectly by increasing the concentration of circulating somatomedins (insulin-like growth factors) has been the subject of controversy. Immunohistochemical methods were used to explore the localization and distribution of insulin-like growth factor I (IGF-I) immunoreactivity in the epiphyseal growth plate of the proximal tibia of male rats. Cells in the proliferative zone of the growth plate of normal rats exhibited a bright immunofluorescence, whereas cells in the germinal and hypertrophic zones stained only weakly. In rats subjected to hypophysectomy, the number of fluorescent cells was markedly reduced. When the hypophysectomized rats were treated with growth hormone, either systemically or at the site of the growth plate, the number of IGF-I-immunoreactive cells in the proliferative zone was increased. The results show that IGF-I is produced in proliferative chondrocytes in the growth plate and that the number of IGF-I-containing cells is directly regulated by growth hormone. These findings suggest that IGF-I has a specific role in the clonal expansion of differentiated chondrocytes and exerts its function locally through autocrine or paracrine mechanisms.     

Facilitation of brain self-stimulation by central administration of norepinephrine

Rats with electrodes implanted in the medial forebrain bundle stimulated their own brains at sharply reduced rates after systemic administration of disulfiram or intraventricular administration of diethyldithiocarbamate. Both drugs inhibit dopamine-beta-hydroxylase, the enzyme responsible for the final step in the biosynthesis of norepinephrine. The suppressed behavior was reinstated by intraventricular injections of 1-norepinephrine, but not by injection of its biologically inactive isomer, d-norepinephrine. Intraventricular administration of dopamine and serotonin did not restore self-stimulation. The rewarding effect of medial forebrain bundle stimulation may depend on the availability of norepinephrine as a transmitter, but not on dopamine or serotonin.     

Neuroleptic-induced "anhedonia" in rats: pimozide blocks reward quality of food

The dopamine receptor blocker pimozide attenuated lever-pressing and running for food reward in hungry rats. In each case the characteristic behavior of pimozide-treated rats was the same as that of undrugged rats when reward was simply withheld. Drug-induced performance difficulties were ruled out by the presence of periods of normal responding in drug-treated animals. Pimozide appears to selectively blunt the rewarding impact of food and other hedonic stimuli.     

帕金森病模型大鼠脑内CDNF表达变化

为了探讨帕金森病(PD)发病过程中大脑多巴胺能神经营养因子(CDNF)表达的变化,以大鼠为模型,研究了帕金森病CDNF及相关基因的表达变化,从而为基因治疗帕金森病提供理论依据。实验采用单侧黑质内单点注射6-羟多巴胺的方法制备帕金森病大鼠模型;运用免疫组织化学、Western blot及Q-PCR方法检测CDNF和多巴胺合成限速酶—酪氨酸羟化酶(TH)在模型大鼠黑质中表达的变化。研究结果发现,PD模型大鼠脑黑质区CDNF和TH阳性细胞数明显减少;进一步研究表明,与正常大鼠相比,模型大鼠CDNF m RNA表达水平虽未见显著改变(P0.05),但CDNF及TH蛋白表达极显著降低(P0.01)。提示帕金森病的发病可能与黑质中CDNF和TH表达量降低,进而抑制多巴胺合成有关。     

罗布麻叶总黄酮提取物对抑郁大鼠脑内单胺类神经递质含量的影响

[目的]探讨罗布麻（Apocynum venetum L.）叶总黄酮提物抗抑郁作用的机理。[方法]采用大鼠慢性应激抑郁模型,利用液相色谱-质谱串联法测定大鼠脑内单胺类神经递质[去甲肾上腺素（NE）、多巴胺（DA）和5-羟色胺（5-HT）]的含量。[结果]慢性应激抑郁组动物组织内DA、5-HT和NE含量与正常组相比均极显著降低（P〈0.01）。罗布麻总叶黄酮提取物处理组大鼠脑中DA和NE含量与慢性应激抑郁组相比显著或极显著上升,且随着剂量的增大,这种作用更加明显;70.0 mg/kg罗布麻叶黄酮提取物处理与盐酸氟西汀（3.5mg/kg）效果一致;但罗布麻叶总黄酮提取物处理组大鼠脑中5-HT含量与慢性应激抑郁组相比没有明显变化,阳性对照药氟西汀显著增加了抑郁大鼠脑组织中DA、NE和5-HT含量。[结论]该研究证实了抑郁症发病的神经递质假说,同时发现罗布麻叶可以逆转抑郁大鼠脑内单胺类物质NE、DA含量的降低,这也可能是其抗抑郁作用的机理之一。     

THE ISOLATION IN PURE FORM OF THE INTERSTITIAL CELL-STIMULATING (LUTEINIZING) HORMONE OF THE ANTERIOR LOBE OF THE PITUITARY GLAND

Interstitial cell-stimulating (luteinizing) hormone was isolated from swine pituitary glands. This protein hormone, having a molecular weight of about 90,000 and an isoelectric point of pH 7.45, was shown to be pure by tests in the electrophoresis apparatus of Tiselius and in the ultracentrifuge as well as by its constant solubility. The hormone stimulated the interstitial tissue of the testis or ovary and caused the formation of corpora lutea provided that maturing follicles were present. Under the conditions described, its minimal effective total dose in hypophysectomized immature male rats was about 1 microgram of nitrogen or 6.7 micrograms of hormone. Extracts of swine pituitary with purely follicle-stimulating effects did not cause oestrus in immature hypophysectomized female rats unless luteinizing hormone was also administered.     

Atrophy of Ovaries Transplanted to the Spleen in Unilaterally Castrated Rats; Proliferative Changes Following Subsequent Removal of Intact Ovary

An ovary placed in the spleen of an animal that has one normal ovary undergoes atrophy that starts as early as 24 days after transplantation. Severe atrophy is reached before 55 days, and subsequent changes are minor. The degree of atrophy is almost as intense as that noted in the hypophysectomized castrate animal with an ovarian transplant in the spleen (2). The transplanted ovary shows no evidence of any type of response to the hormonal influence that has stimulated the ovary that remained in situ. Removal of the normal ovary introduces the hormonal imbalance that was present in the original tumor animals. The atrophic ovarian parenchyma in the spleen in these, as well as in the hypophysectomized animals previously reported, retained its growth potentials and responded to the hormonal forces by assuming the changes that characterized the development of the luteoma. The action of the atrophic ovarian parenchyma is reminiscent of malignant cell deposits that may remain dormant or quiescent for long periods and then, for some unknown reason, suddenly undergo growth.     

Rat fighting behavior: serum dopamine- -hydroxylase and hypothalamic tyrosine hydroxylase

Male Sprague-Dawley rats were subjected to 4 weeks of daily periods of immobilization stress. One of two experimental groups was allowed 1 month of recovery. After 4 weeks of stress, there was a significant increase in shockinduced fighting, in the activity of serum dopamine-beta-hydroxylase, and in the activity of hypothalamic tyrosine hydroxylase. The concentration of hypothalamic norepinephrine was not decreased. After 4 weeks of recovery, only serum dopamine-betahydroxylase activity returned to normal; it therefore appears that longterm stress may increase central catecholamine synthesis. possibly resulting in a persistent increase in aggressive behavior.     

Biosynthesis of norepinephrine in isolated canine heart

Radioactive dopamine was injected into the blood that was perfusing an isolated heart preparation. Analysis of the norepinephrine obtained from the heart 1 hour later demonstrated that it contained radioactivity. Between 1.4 and 10.8 percent of the norepinephrine present had been formed from the dopamine. The turnover of norepinephrine was substantially higher in the ventricles than in the atria.     

Amphetamine: differentiation by d and l isomers of behavior involving brain norepinephrine or dopamine

d-Amphetamine is markedly more potent an inhibitor of catecholamine uptake by norepinephrine neurons in the brain than is 1-amphetamine, whereas the two isomers are equally active in inhibiting catecholamine uptake by the dopamine neurons of the corpus striatum. In behavioral studies, d-amphetamine is ten times as potent as 1-amphetamine in enhancing locomotor activity, while it is only twice as potent in eliciting a compulsive gnawing syndrome. This suggests that the locomotor stimulation induced by amphetamine involves central norepinephrine, while dopamine neurons play an important role in the induced compulsive gnawing behavior. Assessment of differential actions of d- and 1-amphetamine may be an efficient method to differentiate behaviors involving norepinephrine or dopamine in the brain.     

Adenosine 3',5'-monophosphate content in rat caudate nucleus: demonstration of dopaminergic and adrenergic receptors

Dopamine, apomorphine, isoproterenol, and norepinephrine each increased the concentration of adenosine 3',5'-monophosphate in slice of rat caudate nucleus. The concentrations of dopamine, apomorphine isoproterenol, and norepinephrine causing half-maximal increases were 60, 150, 0.03 and 30 micromoles per liter, respectively. The effect of dopamine was blocked by fluphenazine, a dopamine receptor antagonist, but not by propranolol, a beta-andrenergic receptor antagonist. Conversely, the effect of isoproterenol was blocked by propranolol but not by fluphenazine. The results suggest that in rat caudate nucleus there are two distinct catecholamine receptors capable of causing increased concentrations of adenosine 3',5'-monophosphate, one having the characteristic of dopamine receptor, and the other having the characteristics of beta-adrenergic receptor.     

Pineal vasotocin: release into cat cerebrospinal fluid by melanocyte-stimulating hormone release-inhibiting factor

The intracarotid injection of both synthetic melanocyte-stimulating hormone release-inhibiting factor (MIF) and purified MIF prepared from bovine hypothalami induces arginine vasotocin release into cerebrospinal fluid of cats and significantly decreases the pineal arginine vasotocin content at 5 minutes after the injection. The present results demonstrate an extrapituitary endocrine effect of synthetic and purified bovine MIF.