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E Gottberg

Publications and source records attributed to E Gottberg.

8 recordsLinked to original sources

Testosterone modulates mesolimbic dopaminergic activity in male rats.

Male rats were castrated before puberty. When they were adult, the activity of their mesolimbic dopamine system was tested by ventral striatum microdialysis. Amphetamine injections increased dopamine more in castrated rats than in normal rats. This exaggerated response was attenuated by testosterone replacement therapy. The mechanism by which androgens modulate the activity of the mesolimbic dopamine system is discussed.

Amphetamine↗

Acute effects of lithium on catecholamines, serotonin, and their major metabolites in discrete brain regions.

The acute effects of lithium on the central catecholamine and serotonin systems were investigated in well-defined cortical areas in the rat: the anterior cingulate cortex (CIN), the piriform-entorhinal region (PiEn), and the primary visual area (VIS) as well as in the hippocampus (HIP), the neostriatum (CPU; caudateputamen), and the olfactory bulbs (OBs). In these microdissected regions, the catecholamines noradrenaline (NA) and dopamine (DA), the indoleamine 5-hydroxytryptamine (5-HT; serotonin), as well as some of their major metabolites (3-methoxy-4-hydroxyphenylglycol; 3,4-dihydroxyphenylacetic acid; homovanillic acid; 3-methoxytyramine; 5-hydroxy-1-tryptophan; and 5-hydroxyindole-3-acetic acid) were assayed by using high-performance liquid chromatography (HPLC) with electrochemical detection. One hour after the administration of lithium chloride (2 and 10 mEq/kg; i.p.) the endogenous NA levels increased in the CIN and PiEn cortices, in the HIP, and in the CPU. The DA contents remained unchanged in the CPU, HIP, OB, and VIS cortex but were increased in the CIN and PiEn regions. These increases in cortical DA levels were accompanied by reductions in HVA and DOPAC. The levels of HVA and DOPAC but not 3-MT were also reduced in the CPU, in spite of a normal DA content. The discrepancies between changes of DA and the levels of its metabolites indicate changes in the turnover rates as well as an action of lithium on DA synthesis and/or storage in the nigrostriatal and mesocortical systems. The 5-HT contents were also increased by lithium throughout all regions, except for the OB.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Effects of sodium, lithium, and magnesium on in vitro binding of [3H]SCH23390 in rat neostriatum and cerebral cortex.

The effects of sodium, lithium, and magnesium on the in vitro binding properties of the D1 antagonist [3H]SCH23390 were examined with membrane preparations from rat neostriatum (CPU; caudate-putamen) and cerebral cortex (CTX). The saturation binding isotherms for both tissues performed in the presence of 120 mM of either Na+ or Li+ revealed an increase in the affinity, as compared to that observed when the incubation buffer was composed of Tris-Cl 50 mM with MgCl2 1 mM alone. For the CPU there were no changes in the maximum binding capacity (Bmax) in the different buffers used. In the case of the CTX, there was a loss of [3H]SCH23390 binding sites when either Na+ or Li+ 120 mM were added to the incubations, suggesting a lack of selectivity of this ligand in the absence of group IA cations. The agonist state of the [3H]SCH23390 binding site was studied in competition experiments with dopamine. The highest agonist affinity was obtained in 50 mM Tris-Cl buffer with 1 mM MgCl2 while the addition of 120 mM of either Na+ or Li+ caused a 3- to 5-fold decrease in the potency of dopamine to compete with specific [3H]SCH23390 binding in both CPU and CTX. The presence of magnesium was essential for the competition experiments; i.e.: a concentration of 1 mM MgCl2 was optimum to obtain dopamine antagonism of ligand binding, while increasing Mg2+ to 2 or 5 mM did not appear to further improve the inhibitions. The results support both agonist and antagonist affinity shifts for the dopamine D1 receptor labeled with [3H]SCH23390.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of dopamine D1 receptors in rat cortical areas, neostriatum, olfactory bulb and hippocampus in relation to endogenous dopamine contents.

The tritiated dopamine D1 antagonist SCH23390 was employed to determine the densities of D1 receptors in seven discrete and functionally identified cortical areas (cingulate, frontal, parietal, primary somatosensory, primary visual, retrosplenial and entorhinal-piriform) as well as in the neostriatum, hippocampus and olfactory bulbs. In addition, the tissue levels of the catecholamines NA, AD, DA, the indoleamine 5-HT and their main metabolites (MHPG, DOPAC, HVA, 3-MT, 5-HTP and 5-HIAA) were measured in the different regions by HPLC with electrochemical detection. The Scatchard analysis of saturation curves revealed the highest density of [3H]SCH23390 binding sites for the neostriatum, while the densities were 10-20 times lower for total cerebral cortex and hippocampus respectively. For the olfactory bulb and other cortical areas, D1 receptor densities were determined by equilibrium binding at a fixed radioligand concentration approaching saturation. The distribution of D1 receptors was heterogeneous with the greatest densities in entorhinal-piriform and cingulate cortices. The endogenous DA levels measured for all regions correlated with their metabolite (DOPAC, HVA and 3-MT) contents (r = 0.999; P less than 0.001). There was also a very good correlation (r = 0.981; P less than 0.001) between tissue DA and D1 receptor densities. This quantitative information reflects particular features of the organization of the DA systems and is discussed in relation to turnover and recently established aspects of the DA innervation.

Animals↗

Acute effects of lithium on dopaminergic responses: iontophoretic studies in the rat visual cortex.

The interactions between lithium and cortical dopaminergic receptors were investigated using the iontophoretic technique to record and apply dopaminergic compounds, GABA, acetylcholine and LiCl on neurons in the primary visual cortex of the rat. The main responses to dopamine (DA) or to the D1 agonist (+/- )SKF38393 on spontaneously-active (SA) or visually-driven (VD) units was a prolonged decrease in firing and a reduction in the responsiveness to pulses of acetylcholine. The D1 antagonist SCH23390, applied iontophoretically or intravenously, blocked or attenuated the inhibitory responses to both DA and (+/- )SKF38393. The D2 agonist quinpirole (LY171555) either produced only slight excitations or had no effects on both VD and SA units. The concomitant application of lithium blocked the inhibitory responses to DA and to (+/- )SKF38393 but did not modify the responsiveness to LY171555. In addition, the DA- and (+/- )SKF38393-induced decreases in responsiveness to acetylcholine were also suppressed by lithium. These effects were on dopaminergic mechanisms, since the excitatory responses to acetylcholine alone as well as the inhibitions caused by GABA were unchanged by the application of lithium. These results imply that the modifications in sensitivity to dopaminergic agents induced by lithium are mediated by dopamine D1 receptors and are discussed in relation to adenylate-cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Specific [3H]SCH23390 binding to dopamine D1 receptors in cerebral cortex and neostriatum: evidence for heterogeneities in affinity states and cortical distribution.

The tritiated antagonist SCH23390 was used to identify dopamine D1 receptors in the cerebral cortex and neostriatum. The kinetic properties of binding were investigated in parallel experiments with membrane preparations from both tissues. The densities of receptors (Bmax) and the dissociation constants (KD) were determined from saturation curves, and the specificity of binding verified in competition experiments using agonists and antagonists. The cortical D1 receptor displays the same pharmacological selectivity (including stereospecificity) and kinetic properties as the neostriatal D1 receptor. From both the dissociation kinetics by dilution and the competition curves, it could be established that there is an heterogeneity of binding probably due to high- and low-affinity states. Endogenous dopamine, 4-hydroxy-3-methoxyphenylacetic acid, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine contents, as well as D1 receptor distribution, were measured for the neostriatum and four localized cortical areas: anterior cingulate, primary somatosensory, primary visual, and piriform-entorhinal. For the regions examined, the distribution of D1 receptors is heterogeneous, but correlates very well (r greater than 0.98) with the endogenous levels of dopamine and its major metabolites.

Animals↗

Stereospecific binding of a new benzazepine, [3H]SCH23390, in cortex and neostriatum.

The binding of the D1 antagonist SCH23390 to membrane preparations from rat cerebral cortex was examined using enantiomers of dopamine agonists and antagonists to compete with the bound [3H]SCH23390 at its Kd value. The competition curves were compared with those obtained with preparations from the neostriatum. The results demonstrate that specific [3H]SCH23390 binding in the cerebral cortex has the same pharmacological profile as in the neostriatum, so that this radioligand can be used to label dopamine D1 receptors in brain regions with a sparse dopaminergic innervation.

Animals↗