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1.
Enduring changes in dopamine receptor cells of pups from drug administration to pregnant and nursing rats 总被引：4，自引：0，他引：4
A decrease in specific [3H]spiroperidol binding to rat caudate tissue and a parallel decrease in sensitivity to apomorphine in eliciting stereotyped behavior was observed in the offspring of rat mothers treated with either haloperidol or alpha-methyl-p-tyrosine-methyl ester during pregnancy. In contrast, evidence of increased dopamine-receptor sensitivity was observed in the pups if haloperidol was administered to their mothers postpartum during nursing rather than during pregnancy. 相似文献
2.
Perinatal dopamine-related drugs demasculinize rats 总被引：2，自引：0，他引：2
Administration of haloperidol, a common neuroleptic, to pregnant or lactating rats impaired the masculine sex behavior of their male offspring. Prenatal haloperidol did not affect testosterone concentrations in fetuses. Maternal administration of apomorphine, a dopamine agonist, and of alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis, also demasculinized male offspring. In both experiments other behaviors and developmental milestones were unaffected. Perinatal haloperidol, apomorphine, and alpha-methyl-p-tyrosine did not lower testosterone in adulthood. These drugs may act directly on neurons that control masculine behavior without lowering testosterone prenatally or in adulthood. 相似文献
3.
Ascorbic acid and the behavioral response to haloperidol: implications for the action of antipsychotic drugs 总被引：1，自引：0，他引：1
Haloperidol, a widely used antipsychotic drug, was tested for its ability to block the behavioral response to amphetamine and to elicit catalepsy in rats treated with saline or ascorbic acid (1000 milligrams per kilogram of body weight). By itself, ascorbic acid failed to exert significant behavioral effects, but it enhanced the antiamphetamine and cataleptogenic effects of haloperidol (0.1 or 0.5 milligrams per kilogram). These results, combined with a growing body of biochemical evidence, suggest that ascorbic acid plays an important role in modulating the behavioral effects of haloperidol and related antipsychotic drugs. 相似文献
4.
The hyperthermic response of rabbits to apomorphine, a dopaminergic agonist, is abolished by prior treatment with p-chlorophenylalanine. If such 5-hydroxytryptamine (5-HT)-depleted animals are administered a peripherally acting decarboxylase inhibitor plus 5-hydroxytryptophan, central stores of 5-HT are regenerated and the hyperthermic response to apomorphine is restored in part. The effects of apomorphine in rabbits with elevated concentrations of 5-HT are not different from those in control animals. The behavioral effects of apomnorphine appear to be constant in all groups of animals tested. It is suggested that the hyperthermic effects of apomorphine in rabbits require the presence of 5-HT. 相似文献
5.
Normalization of spiroperidol binding in the denervated rat striatum by homologous grafts of substantia nigra 总被引：3，自引：0，他引：3
W J Freed G N Ko D L Niehoff M J Kuhar B J Hoffer L Olson H E Cannon-Spoor J M Morihisa R J Wyatt 《Science (New York, N.Y.)》1983,222(4626):937-939
Transplantation of embryonic substantia nigra into the adult rat brain decreases the motor asymmetry that is produced by dopamine receptor supersensitivity after a unilateral lesion of the substantia nigra. The authors report that this effect of transplantation is specific to grafts of substantia nigra. They also report that, in conjunction with the decrease in motor asymmetry, these grafts cause postsynaptic dopaminergic binding sites to return to normal density as measured by tritiated spiroperidol autoradiography. Thus, in animals with brain lesions, grafts of substantia nigra produce a long-term alteration in the functional status of host brain cell receptors that is associated with a reduction in the behavioral deficit. 相似文献
6.
Adenosine 3',5'-monophosphate content in rat caudate nucleus: demonstration of dopaminergic and adrenergic receptors 总被引：6，自引：0，他引：6
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. 相似文献
7.
D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects 总被引：15，自引：0，他引：15
J R Walters D A Bergstrom J H Carlson T N Chase A R Braun 《Science (New York, N.Y.)》1987,236(4802):719-722
D1 and D2 dopamine receptors exert synergistic effects on the firing rates of basal ganglia neurons and on the expression of stereotyped behavior in rats. Moreover, the ability of D2 agonists to induce changes in basal ganglia single unit activity and spontaneous motor activity is dependent upon the presence of endogenous dopamine to stimulate D1 receptors; in rats treated with alpha-methyl-rho-tyrosine to reduce endogenous dopamine levels, the neurophysiological and behavioral effects of the D2 agonist quinpirole are significantly attenuated, while the effects of nonselective agonists like apomorphine, which stimulate both D1 and D2 receptors, or combinations of a D2 agonist and a D1 agonist are not attenuated. Thus, the previously held view that D2 receptors alone are responsible for evoking the changes in behavior and basal ganglia output induced by nonselective dopamine agonists and endogenous dopamine is not supported by these results, which indicate that these phenomena require concurrent stimulation of both dopamine receptor subtypes. 相似文献
8.
People typically exhibit greater sensitivity to losses than to equivalent gains when making decisions. We investigated neural correlates of loss aversion while individuals decided whether to accept or reject gambles that offered a 50/50 chance of gaining or losing money. A broad set of areas (including midbrain dopaminergic regions and their targets) showed increasing activity as potential gains increased. Potential losses were represented by decreasing activity in several of these same gain-sensitive areas. Finally, individual differences in behavioral loss aversion were predicted by a measure of neural loss aversion in several regions, including the ventral striatum and prefrontal cortex. 相似文献
9.
Neuroleptic drug-induced dopamine receptor supersensitivity: antagonism by L-prolyl-L-leucyl-glycinamide 总被引：1，自引：0，他引：1
An animal model of tardive dyskinesia was used to evaluate the potential antidyskinetic properties of the neuropeptide L-prolyl-L-leucyl-glycinamide (PLG). In rats, PLG administered concurrently with the neuroleptic drug haloperidol or chlorpromazine antagonized the enhancement of specific [3H]spiroperidol binding in the striatum that is associated with long-term neuroleptic treatment. The results are discussed in relation to a possible functional coupling of the putative PLG receptor with neuroleptic-dopamine receptor complex and clinical implications for tardive dyskinesia. 相似文献
10.
Bäckman L Nyberg L Soveri A Johansson J Andersson M Dahlin E Neely AS Virta J Laine M Rinne JO 《Science (New York, N.Y.)》2011,333(6043):718
Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory. 相似文献
11.
When placed in a tank of water, aged rats (24 to 27 months old) showed marked impairments in swimming. Compared with young adult rats (3 to 4 months old), the older animals moved their limbs less vigorously and were less successful in keeping their heads above water. The young, but not old, rats maintained a position nearly horizontal to the water surface and planed across it. These movement dysfunctions of aged rats resemble those seen in young adult animals that have sustained injury to brain dopamine-containing neurons. The swimming impairments of the aged rats were reversed by the dopamine receptor stimulant apomorphine and by the biosynthetic precursor of dopamine, L-dopa. Thus, age-related alterations in brain dopaminergic systems may be responsible for some of the movement disturbances associated with senescence. 相似文献
12.
Refojo D Schweizer M Kuehne C Ehrenberg S Thoeringer C Vogl AM Dedic N Schumacher M von Wolff G Avrabos C Touma C Engblom D Schütz G Nave KA Eder M Wotjak CT Sillaber I Holsboer F Wurst W Deussing JM 《Science (New York, N.Y.)》2011,333(6051):1903-1907
The corticotropin-releasing hormone receptor 1 (CRHR1) critically controls behavioral adaptation to stress and is causally linked to emotional disorders. Using neurochemical and genetic tools, we determined that CRHR1 is expressed in forebrain glutamatergic and γ-aminobutyric acid-containing (GABAergic) neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs neurotransmission in the amygdala and hippocampus. Selective deletion of CRHR1 in midbrain dopaminergic neurons increases anxiety-like behavior and reduces dopamine release in the prefrontal cortex. These results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders. 相似文献
13.
Klein TA Neumann J Reuter M Hennig J von Cramon DY Ullsperger M 《Science (New York, N.Y.)》2007,318(5856):1642-1645
The role of dopamine in monitoring negative action outcomes and feedback-based learning was tested in a neuroimaging study in humans grouped according to the dopamine D2 receptor gene polymorphism DRD2-TAQ-IA. In a probabilistic learning task, A1-allele carriers with reduced dopamine D2 receptor densities learned to avoid actions with negative consequences less efficiently. Their posterior medial frontal cortex (pMFC), involved in feedback monitoring, responded less to negative feedback than others' did. Dynamically changing interactions between pMFC and hippocampus found to underlie feedback-based learning were reduced in A1-allele carriers. This demonstrates that learning from errors requires dopaminergic signaling. Dopamine D2 receptor reduction seems to decrease sensitivity to negative action consequences, which may explain an increased risk of developing addictive behaviors in A1-allele carriers. 相似文献
14.
Striatal nondopaminergic neurons: possible involvement in feeding and drinking behavior 总被引：1，自引：0，他引：1
D J Pettibone N Kaufman M C Scally E Meyer I Ulus L D Lytle 《Science (New York, N.Y.)》1978,200(4346):1175-1177
Intracaudate injections of kainic acid destroy striatal neurons containing acetylcholine and gamma-aminobutyric acid but leave dopaminergic nerve terminals in this brain region intact. Rats injected with the drug are aphagic and adipsic, and have other behavioral abnormalities strikingly similar to those seen in animals with lesions in the dopaminergic nigrostriatal bundle. 相似文献
15.
随着经济发展、人们生活方式改变,糖尿病已严重威胁人类健康。胰岛素抵抗是2型糖尿病发生的关键因素,从胰岛素合成后与胰岛素受体结合到实现生理效应的一系列过程中,都可能发生异常。运动疗法能够提高组织对胰岛素的敏感性,提高机体维持血糖稳定的激素调节能力。查阅了近年来国内外有关运动干预骨骼肌胰岛素功能的研究情况,分析了运动对骨骼肌胰岛素影响的主要因素,以及不同运动形式对骨骼肌胰岛素的影响。 相似文献
16.
Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding 总被引：20，自引：0，他引：20
Mononuclear blood cells were obtained from a patient with type A insulin resistance. The cells showed a normal ability to bind iodine 125-labeled insulin. Analysis of solubilized insulin receptors from the patient's cells revealed a defect in insulin-stimulated tyrosine kinase activity, which is closely associated with the receptor itself. The enzyme failed to phosphorylate the insulin receptor and showed a markedly reduced ability to phosphorylate exogenously added substrates. It appears that receptors from this insulin-resistant patient have a defect distal to the insulin-binding site (the alpha subunit of the receptor). The defect could be located in the beta subunit, which has an adenosine triphosphate-binding site, or in another receptor component that transfers a signal of insulin binding into kinase activity. This dissociation between the normal binding and the defective protein kinase component of the insulin receptor represents the first biochemical defect of the receptor distal to ligand binding. 相似文献
17.
Dissociated cell suspensions, prepared from the substantia nigra and septal regions of rat embryos, can be grafted to the depths of the caudate-putamen and hippocampus of aged rats. The grafts were rich in dopamine-containing and acetylcholinesterase-positive neurons and had produced extensive new dopaminergic and cholinergic terminal networks in the host neostriatum and hippocampus, respectively. The intrastriatal dopaminergic grafts were associated with a significant improvement in motor coordination in the aged rats. This result suggests that the intracerebral grafting technique may provide a new tool for exploring the role of dopaminergic and cholinergic deficits in the neurological and behavioral impairments associated with aging. 相似文献
18.
beta-Adrenergic regulation of alpha 2-adrenergic receptors in the central nervous system 总被引：1，自引：0，他引：1
Incubation of rat cerebral cortical slices with the beta-adrenergic agonist isoproterenol causes an increase in alpha 2-adrenergic receptor binding in addition to a decrease in beta-adrenergic receptor binding. The effects are rapid and reversible, show a parallel time course, and are blocked by sotalol, a beta-adrenergic receptor antagonist. The beta-mediated regulation of alpha 2-receptor sensitivity at brain norepinephrine synapses may be a mechanism for the homeostatic control of central noradrenergic activity. 相似文献
19.
Insulin-resistant diabetes due to a point mutation that prevents insulin proreceptor processing 总被引：21，自引：0，他引：21
Y Yoshimasa S Seino J Whittaker T Kakehi A Kosaki H Kuzuya H Imura G I Bell D F Steiner 《Science (New York, N.Y.)》1988,240(4853):784-787
A point mutation in the human insulin receptor gene in a patient with type A insulin resistance alters the amino acid sequence within the tetrabasic processing site of the proreceptor molecule from Arg-Lys-Arg-Arg to Arg-Lys-Arg-Ser. Epstein-Barr virus-transformed lymphocytes from this patient synthesize an insulin receptor precursor that is normally glycosylated and inserted into the plasma membrane but is not cleaved to mature alpha and beta subunits. Insulin binding to these cells is severely reduced but can be increased about fivefold by gentle treatment with trypsin, accompanied by the appearance of normal alpha subunits. These results indicate that proteolysis of the proreceptor is necessary for its normal full insulin-binding sensitivity and signal-transducing activity and that a cellular protease that is more stringent in its specificity than trypsin is required to process the receptor precursor. 相似文献
20.
Behavioral sensitivity to purinergic drugs parallels ethanol sensitivity in selectively bred mice 总被引：6，自引：0，他引：6
Behavioral responses to an adenosine receptor agonist and antagonist were examined in mice genetically selected for differential sensitivity to the soporific effects of ethanol. Both ethanol and the adenosine receptor agonist L-phenylisopropyladenosine had greater sedative and hypothermic effects in ethanol-sensitive "long-sleep" mice than in ethanol-insensitive "short-sleep" mice. Long-sleep mice were also more sensitive to the excitatory behavioral effects of theophylline, an adenosine receptor antagonist. These data suggest that adenosine may be an endogenous mediator of responses to ethanol. 相似文献