An Association Between a Microsatellite Polymorphism at the DRD5 Gene and the Liability to Substance Abuse: Pilot Study

We have conducted a population-based association study of substance abuse and a microsatellite at the dopamine D5 receptor locus (DRD5) in a sample of European–American males and females with substance dependence (SA) or without any psychiatric disorder. Overrepresentation of the most frequent allele (148 bp) was found in males in the SA group (OR = 2.2, P= .02); this finding was reproduced in females (OR = 5.4, p< .001). The difference in the frequencies of this allele between SA males and SA females was statistically significant. The genotype coded in accordance with the dose of this allele correlated with substance abuse liability in males and females (stronger in females) and with novelty seeking in females. There was no evidence of correlation between the genotypes of spouses that could be induced by assortative mating for the liability to substance abuse. The data suggest that the DRD5 locus is involved in the variation and sex dimorphism of substance abuse liability.CEDAR is a consortium between St. Francis Medical Center and the University of Pittsburgh.     

The ''M2'' electromyographic response to random perturbations of arm movements is missing in long-trained monkeys

Post-trial injections of norepinephrine, but not dopamine, into the amygdala produce a long-term retention deficit (amnesia) for a 1-trial footshock experience in rats. In contrast, post-trial injections of dopamine, but not norepinephrine, into the caudate produce long-term facilitation. The data provide evidence for brain region-neurotransmitter specificity which supports a multiple component hypothesis.     

鸡后根神经节多巴胺细胞在体及体外培养中的免疫细胞化学观察

应用免疫细胞化学PAP法,研究了鸡胚和雏鸡后根神经节细胞内多巴胺递质的表现与胚胎发育过程中的变化,并在细胞培养条件下研究了周围靶组织——皮肤对后根节细胞胚胎发育的影响。鸡后根节细胞内多巴胺的免疫反应最先出现于E_(10),只占后根节细胞的0.8%,E_(18)时达5.6%,出壳后雏鸡为8.6%。在鸡后根节内,多巴胺免疫反应阳性细胞主要为较大的A类细胞,和极少较小的B类细胞。免疫反应阳性的周围神经末梢位于皮肤和交感干内。当取自E_9的鸡胚后根节细胞经7天培养后,部分神经细胞出现多巴胺免疫反应阳性;而取自E_6的鸡胚后根节细胞虽经10天培养后仍为免疫反应阴性;然而,将取自E_6后根节细胞与皮肤组织联合培养10天后,少量神经细胞及轴突出现多巴胺免疫阳性反应。作者认为:鸡后根节多巴胺细胞在胚胎时期的发育有赖于周围靶组织的作用。     

Linkage analysis between manic-depressive illness and markers on the long arm of chromosome 11

The long arm of chromosome 11 is one of the most interesting regions in the search for major genes involved in the etiology of manic-depressive illness. Several candidate genes have been identified, including the gene encoding the dopamine D2 receptor, the M1 muscarinic receptor, and porfobillinogen deaminase. Furthermore, different families with co-segregation of psychiatric illness and structural chromosome abnormalities involving regions 11q21, 11q22.3, and 11q25 have been reported. Using narrow as well as broad phenotypic models, conservative genetic parameters, models with dominant or recessive modes of inheritance, and various methods to reduce misclassification, the present study did not find evidence for a major gene causing manic-depressive illness on the long arm of chromosome 11. In the broader phenotypic models multi-point analyses excluded at least 11q14 to 11q23.3, approximately 60 cM, even in one large family. Assuming homogeneity close linkage to DRD2 was excluded for all dominant models, and also in the affecteds-only analyses in the large family alone. © 1995 Wiley-Liss, Inc.     

Muscle relaxant action of excitatory amino acid antagonists

Antagonists of neuronal excitation induced by dicarboxylic amino acids were tested in genetically spastic rats of the Han-Wistar strain. These animals exhibit an increased muscle tone which can be measured as a spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Compounds that block excitation due to N-methyl-D-aspartic acid reduced the spontaneous activity measured in the electromyogram in a dose-related manner. The most potent compounds, 2-amino-7-phosphonoheptanoic and kynurenic acids were effective muscle relaxants when given either intraperitoneally or intracerebroventricularly. 2-Amino-5-phosphonopentanoic acid possessed much weaker muscle relaxant activity, while L-glutamic acid diethylester was inactive by either route. The results suggest that blockade of N-methyl-D-aspartic acid receptors results in a myorelaxant effect. Specific antagonists of excitation at N-methyl-D-aspartic acid receptors may provide a new class of muscle relaxants.     

Comparison of Changes in Glutamate Levels in the Nucleus Accumbens of the Rat Brain during Food Consumption in Conditions of Blockade of Dopamine D1 and D2 Receptors

The effects of blockade of D₁ and D₂ dopamine receptors in the nucleus accumbens on changes in glutamate levels in the intercellular space of this structure during food consumption were studied in Sprague–Dawley rats by intracerebral microdialysis combined with HPLC. These experiments showed that food consumption was accompanied by decreases in glutamate levels in the intercellular spaces of the nucleus accumbens. Blockade of D₁ dopamine receptors with SCH-23390 (0.01 mM) produced no changes in the dynamics of glutamate release during food consumption. Food consumption in conditions of blockade of D₂ dopamine receptors with raclopride (0.01 mM) induced increases in glutamate levels. These data suggest that glutamate levels during food consumption are controlled by the dopaminergic system of the nucleus accumbens, mediated by D₂ but not D₁ dopamine receptors.     

Immunofluorescent evidence for exocytosis and internalization of secretory granule membrane in isolated chromaffin cells

Cultured bovine adrenal medullary chromaffin cells were stimulated with the secretogogues Ba2+ or carbamyl choline plus Ca2+ in the presence of a monospecific rabbit IgG fraction directed against bovine dopamine beta-hydroxylase. The anti-dopamine beta-hydroxylase was labeled either with fluorescent protein A or with a fluorescent second antibody to rabbit IgG. Stimulation produced a patchy cell surface distribution of fluorescence. There was no noticeable internalization of the fluorescence for up to 2 h. In similar experiments using fluorescent monovalent fragments (Fab) of the same monospecificidopamine-beta-hydroxylase IgG, a more uniform distribution of the fluorescence was observed. A few min after a 5 min period of stimulation with Ba2+, the fluorescence appeared to be on or near the cell surface; however, after 20 min or more it was distributed throughout the cytoplasm except that the cell nuclei were not labeled. Thus, dopamine beta-hydroxylase which appeared on the cell surface as a consequence of exocytosis was internalized in the presence of monovalent antibody fragments, but not in the presence of the divalent (polyclonal) antibody, presumably because endocytosis of dopamine beta-hydroxylase was inhibited by crosslinking of the dopamine beta-hydroxylase molecules. The internalized anti-dopamine beta-hydroxylase Fab fragments were found to reappear on the cell surface during a second secretory response. It is concluded that the interior of the chromaffin granule membrane, for which dopamine beta-hydroxylase is a marker, becomes exposed on the surface of the cell during secretion and that the membrane is then retrieved back into the cell where it can be re-used in a further secretory cycle.     

Dopamine and methionine-enkephalin in human brain

The contents of dopamine (determined radioenzymatically) and methionine-enkephalin (assayed by a radioimmunoassay) were measured in several areas of the human brain. The peptide was principally localized in dopamine-rich structures. In patients with Parkinson's disease, in contrast to the general dopamine deficiency, the reduction in methionine-enkephalin was restricted to the mesencephalon, putamen and lateral pallidum.     

Voltammetry in unanesthetized rat: Increases of striatal dopamine turnover after unilateral haloperidol injection into the substantia nigra

In freely moving rats, effects of unilateral haloperidol injection into the substantia nigra were monitored with in vivo voltammetry in the bilateral striata. The electrochemical responses at 120 mV versus Ag-AgCl, reflecting mainly a level of 3,4-dihydroxyphenylacetic acid (DOPAC), increased both in the striata within 1.5 h after 5 μg of haloperidol treatment. In the experiments of high-performance liquid chromatography with electrochemical detection, the ratio of DOPAC to dopamine in the striata significantly increased at 2.75 h after drug treatment. These data support the idea that unilateral injection of haloperidol into the substantia nigra in freely moving rats increases dopamine turnover in the bilateral striata.