Search Results - (Author, Cooperation:V. A. Russell)

2015-11-19

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0028-0836

1476-4687

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1573-6903

Dopamine ; noradrenaline ; serotonin ; nucleus accumbens ; regional distribution

Springer Online Journal Archives 1860-2000

Medicine

Abstract Monoamine concentrations were low in the rostral area of the nucleus accumbens. Their distributions were not identical. Differences were observed in the medial area. DA concentrations were high in both medial and caudal areas. Noradrenaline (NA) and serotonin (5-HT) concentrations were considerably lower than the dopamine (DA) concentration. The NA concentration was highest in the caudal area of the nucleus accumbens and the (5-HT) concentration was highest in the ventrocaudal area. There was a rostrocaudal decrease in the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and 5-hydroxyindole-3-acetic acid (5-HIAA)/5-HT ratios. Uptake of [3H]DA and [14C]choline was lowest in the rostral area. The K+-stimulated release of [14C]acetylcholine (ACh) was also lowest rostrally, but there was no rostrocaudal difference in the K+-stimulated release of [3H]DA. These results provide further evidence of the heterogeneity of the nucleus accumbens.

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1573-6903

HPA axis ; hippocampus ; corticosterone ; kainic acid ; pyramidal cells

Springer Online Journal Archives 1860-2000

Medicine

Abstract The aim of the present study was to investigate whether the hiopocampus exerts a modulatory effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Kainic acid was stereotaxically injected into the CA1 pyramidal cell layer of the dorsal hippocampus, causing histological and behavioural changes typical of kainic acid toxicity. The CA3 pyramidal cells of the dorsal hippocampus were selectively lesioned. Rats treated with kainic acid were hyperactive, executed clockwise rotatory movements and displayed epileptic seizures. The acute excitatory effect of kainic acid on glutamatergic receptors in the hippocampus resulted in an elevation in plasma corticosterone levels, suggesting a stimulation of HPA axis activity. Direct or indirect stimulation of the CA1 pyramidal cells of the dorsal hippocampus appeared to have caused the increase in corticosterone secretion.

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1573-6903

Springer Online Journal Archives 1860-2000

Medicine

Abstract The modulatory effects of noradrenergic agonists on the 25 mM K+-induced release of [3H]dopamine (3H-DA) from rat brain nucleus accumbens slices was investigated, using a superfusion technique. The K+-induced release of3H-DA was Ca2+ dependent, significantly enhanced (25–32%;p〈0.02) by the β-adrenoceptor agonist isoproterenol (10 μM), and significantly decreased (13–25%;p〈0.05) by the α2-adrenoceptor agonist clonidine (10 μM). At these concentrations neither drug affected basal release of3H-DA. Clonidine (100 μM) increased the basal release of3H-DA, while decreasing the K+-induced release by 19% (p〈0.01). The inclusion of desipramine in the incubation medium, to prevent accumulation of3H-DA into noradrenergic neurons, did not alter the inhibitory effect of clonidine (10 μM) on3H-DA release. This study provides direct evidence that noradrenergic neurons can modulate dopaminergic neurotransmission in the mesolimbic system.

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1573-6903

Springer Online Journal Archives 1860-2000

Medicine

Abstract In order to test whether co-administration of a serotonin precursor with antidepressant drugs could potentiate the effects of the antidepressants on monoamines or adrenoceptors in rat brain,l-tryptophan (20 mg/kg) was administered to rats daily for 7 or 15 days, either alone or in combination with desipramine (10 mg/ kg) or amitriptyline (10 mg/kg). After treatment withl-tryptophan for 7 days, increases were observed in rat hypothalamic and frontal cortex 5-hydroxy-3-indoleacetic acid levels as well as in hypothalamic dopamine and nucleus accumbens 3,4-dihydroxyphenylacetic acid levels. After 15 days, hippocampal β-adrenoceptor density was found to be decreased. There was no evidence of potentiation of desipramine or amitriptyline action whenl-tryptophan was administered in combination with the antidepressants. On the contrary, the antidepressants appeared to interact withl-tryptophan to reduce its effects.

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1573-6903

Dopamine ; D1-receptor ; D2-receptor ; monoamines ; striatum ; regional distribution

Springer Online Journal Archives 1860-2000

Medicine

Abstract Dopamine (DA) D1-and D2-receptor densities were determined in 18 discrete areas of the caudate-putamen-globus pallidus of male Wistar rats and compared to local DA concentrations. All three parameters were found to decrease caudally. The globus pallidus was distinguished by the low concentration of DA and its receptors and high noradrenaline, (NA) content. While there were no mediolateral differences in DA or DA D1-receptors, a clear mediolateral gradient was observed for DA D2-receptors which extended over several sections of the brain. The ratio of DA D1-to D2-receptors was significantly higher in the dorsal than in the ventral areas of the mediolateral and caudal striatum. This is the first report of clear dorsoventral differences in parameters relating to DA activity in the striatum. These findings may be of particular significance in understanding the functional dichotomy between the dorsal and ventral striatum.

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1573-6903

Corticosterone ; medial forebrain bundle ; lesion ; clonidine ; isoproterenol

Springer Online Journal Archives 1860-2000

Medicine

Abstract Bilateral injection of 6-hydroxydopamine into the medial forebrain bundle (MFB) significantly decreased monoamine concentrations in the hypothalamus. The noradrenaline and serotonin content of the paraventricular nucleus (PVN) was also significantly reduced. These drastic decreases in neurotransmitter concentration did not alter basal secretion of corticosterone. Isoproterenol. a β-adrenoceptor agonist (1 mg/kg, i.p.), significantly stimulated corticosterone release in saline and MFB lesioned rats. This stimulation did not differ significantly between the two groups. Clonidine, an α2-adreceptor agonist, injected either intraperitoneally or intracerebrally just dorsal to the PVN, caused a dose-dependent increase in corticosterone secretion. The stimulation of corticosterone release by clonidine (250 μg/kg, i.p.) was antagonised by the selective α2-adreceptors antagonist, yohimbine (1 mg/kg, i.p.) and significantly reduced by the MFB lesion. These results suggest that corticosterone secretion is stimulated by activation of α2-adreceptors which occur on noradrenergic nerve terminals in the PVN.

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1573-6903

Springer Online Journal Archives 1860-2000

Medicine

Abstract δ-Aminolaevulinic acid (ALA) has been shown to be toxic to cultured neurons and glia at concentrations as low as 10 μM. In an attempt to elucidate the mechanism of toxicity, the effects of ALA on membrane ATPase activity were investigated. Exposure of neuron cultures to 1 mM ALA for 7 days caused a substantial decrease in both Na+, K+-ATPase and Mg2+-ATPase activities. At lower concentrations, ALA affected only the Na+, K+-component. ALA appeared to act directly, inhibiting Na+, K+-ATPase activity in rat brain cortex membrane preparations at 10 μM Although this effect was slight, it may well represent the mechanism of action of ALA, since ouabain, a potent inhibitor of Na+, K+-ATPase activity, proved to be more toxic to cultured neurons than ALA. Furthermore, cardiac glycoside overdosage causes neurological disturbances which are very similar to those observed in the acute attack of porphyria.

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1573-6903

Serotonin ; nucleus accumbens ; striatum ; dopamine release

Springer Online Journal Archives 1860-2000

Medicine

Abstract The effect of serotonin agonists on the depolarization (K+)-induced, calcium-dependent, release of [3H]dopamine (DA) from rat nucleus accumbens and striatal slices was investigated. Serotonin enhanced basal3H overflow and reduced K+-induced release of [3H]DA from nucleus accumbens slices. The effect of serotonin on basal3H overflow was not altered by the serotonin antagonist, methysergide, or the serotonin re-uptake blocker, chlorimipramine, but was reversed by the DA re-uptake carrier inhibitors nomifensine and benztropine. With the effect on basal overflow blocked, serotonin did not modulate K+-induced release of [3H]DA in the nucleus accumbens or striatum. The serotonin agonists, quipazine (in the presence of nomifensine) and 5-methoxytryptamine, did not significantly affect K+-induced release of [3H]DA in the nucleus accumbens. This study does not support suggestions that serotonin receptors inhibit the depolarization-induced release of dopamine in the nucleus accumbens or striatum of the rat brain. The present results do not preclude the possibility that serotonin may affect the mesolimbic reward system at a site which is post-synaptic to dopaminergic terminals in the nucleus accumbens.

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1573-6903

Ethanol ; nucleus accumbens ; striatum ; dopamine release ; acetylcholine

Springer Online Journal Archives 1860-2000

Medicine

Abstract Ethanol (10–200 mM) transiently increased tritium overflow from superfused rat nucleus accumbens slices previously incubated with [3H]dopamine (DA) and [14C]choline. The effect was greater in striatal tissue and did not appear to be a non-specific membrane effect since [14C]acetylcholine (ACh) release was not affected. Lack of antagonism by picrotoxin suggested that γ-aminobutyric acid (GABA) receptors were not involved. Calcium was not a requirement and the DA uptake blocker, nomifensine, was without effect. Ethanol appeared to be causing [3H]DA release into the cytoplasm. K+-stimulated release of [3H]DA and [14C]ACh from nucleus accumbens and striatal slices was not affected. Clonidine-mediated inhibition of the K+-evoked release of [3H]DA remained unaltered. Ethanol attenuated the isoproterenol-induced enhancement of [3H]DA release. Ethanol therefore appeared to interact with components of the DA terminal causing a transient increase in the release of neurotransmitter without impairing K+-evoked release but apparently interfering with the isoproterenol-induced effect.

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1573-6903

DSP4 ; nucleus accumbens ; noradrenaline ; dopamine

Springer Online Journal Archives 1860-2000

Medicine

Abstract DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) treatment (50 mg/kg i.p., 10 days previously) significantly decreased the noradrenaline (NA) content of the rostral part of the nucleus accumbens. The medial and caudal areas were not affected. The nucleus accumbens appears to receive noradrenergic innervation predominantly from subcoeruleus nuclei of the pons-medulla while the locus coeruleus neurons project to the rostral area. The isoproterenol-induced enhancement of the K+-evoked release of [3H]dopamine (DA) was not affected by DSP4 treatment. Noradrenergic denervation does not appear to have been sufficient to cause up-regulation of postsynaptic β-adrenoceptors.

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1573-6903

DA/ACh release ; DA D1/D2-receptors ; nucleus accumbens ; desipramine

Springer Online Journal Archives 1860-2000

Medicine

Abstract The binding of [3H]SCH 23390 to dopamine (DA) D1-receptors was measured in the nucleus accumbens of rats treated chronically with desipramine for 14 days. DA D1 — and D2-receptor binding using [3H]SCH 23390 and [3H]spiperone, respectively as ligands, was determined in rats treated for 28 days. NeitherB max norK d values were influenced by chronic desipramine treatment. In addition, chronic desipramine treatment (28 days) did not influence the dose dependent, quinpirole (10–1000 nM)-mediated inhibition of the electrically stimulated release of [3H]DA and [14C]ACh from nucleus accumbens slices or the dose dependent increase in [3H]DA release and decrease in [14C]ACh release in the presence of 1 and 10 μM nomifensine. Therefore, our results suggest that the effect of chronic antidepressant treatment cannot be attributed to changes in either DA D11-or D2-receptor binding or DA D2-receptor function in the nucleus accumbens.

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1573-6903

Dopamine ; D2 receptors ; nucleus accumbens ; acetylcholine ; quinpirole ; sulpiride

Springer Online Journal Archives 1860-2000

Medicine

Abstract Dopamine (DA) D2 receptor-mediated inhibition of the K+-stimulated release of [14C]acetylcholine (ACh) from prelabeled rat dorsomedial nucleus accumbens slices was found to be 1.7 times greater than that observed in dorsorostral and ventromedial slices. This observation is consistent with the 1.9 fold higher DA D2 receptor density found in the dorsomedial area. In contrast, there were no differences in the DA D2 receptor-mediated effects on [3H]DA release in these areas. In addition, DA D2 receptor-mediated effects on [3H]DA and [14C]ACh release could not be demonstrated in the ventrorostral part of the nucleus accumbens consistent with the fact that DA D2 receptors were barely detectable in this area. The results suggest that cholinergic terminals in the dorsomedial part of the nucleus accumbens are under greater inhibitory DA control than in other areas of the nucleus accumbens.

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1573-6903

Dopamine ; release ; nucleus accumbens ; α2-adrenoceptor ; dopamine D2-receptor ; UK14304

Springer Online Journal Archives 1860-2000

Medicine

Abstract The α2-adrenoceptor agonist, UK14304, dose-dependently inhibited the electrically stimulated release of dopamine (DA) from rat nucleus accumbens slices. This effect was antagonized by idazoxan, confirming that it was an α2-adrenoceptor mediated effect. There was no evidence of endogenous activation of noradrenergic receptors suggesting that the α2-adrenoceptor agonist was not acting presynaptically to inhibit noradrenaline release. An in vitro superfusion technique was used to investigate wheher there was any interaction between α2-adrenoceptors and DA D2-receptors in mediating their inhibitory effects on [3H]DA release from rat nucleus accumbens slices. α2-Adrenoceptor and DA D2-receptors interact with similar second messenger systems and it was considered that they may compete for a common pool of G-proteins. The inhibitory effects of the α2-adrenoceptor agonist, UK14304, and the DA receptor agonists, quinpirole, apomorphine and pergolide were not independent. However, there was no evidence of any interaction between UK14304 and the DA D2-receptor antagonists, sulpiride or haloperidol, suggesting that the two receptors do not compete for a common pool of G-proteins in mediating their inhibitory effects on DA release.

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1573-6903

GH ; DSP4 ; 6-OHDA ; MFB ; lesion ; clonidine ; isoproterenol ; PVN

Springer Online Journal Archives 1860-2000

Medicine

Abstract The aim of the present investigation was to lesion the noradrenergic system and to measure the effect on growth hormone (GH) secretion following peripheral administration of α2- and β-adrenoceptor agonists. Direct injection of these agonists into the paraventricular nucleus of the hypothalamus (PVN) and its effect on GH secretion were also investigated. Systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4, 60 mg/kg, injected i.p. 10 days prior to experimentation) significantly decreased the noradrenaline (NA) content of the hippocampus, frontal cortex and hypothalamus but had no effect on the dopamine (DA) or serotonin (5-HT) content of these areas. Bilateral injection of 6-hydroxydopamine (6-OHDA, 10 μg/μl, 14 days prior to experimentation) into the medial forebrain bundle (MFB) caused a greater reduction of NA and also decreased the DA and 5-HT content of the hypothalamus. Analysis of the PVN of the hypothalami of rats following 6-OHDA lesion of the MFB showed significantly decreased NA and 5-HT content. Neither DSP4 treatment nor 6-OHDA lesion of the MFB affected the clonidine (250 μg/kg, i.p.) induced stimulation of GH secretion. Injection of isoproterenol (1 mg/kg, i.p.) had varying effects on GH secretion. It stimulated GH release in control rats but not in DSP4 or MFB lesioned rats. Direct injection of clonidine (0.1 μg/μl) into the PVN significantly stimulated GH secretion, whereas injection of isoproterenol (2.5 μg/μl) into the PVN did not affect GH levels when compared to controls. The results of the present study do not support the hypothesis that hypoactivity of the central noradrenergic system may be the cause of the blunted GH response to clonidine observed in depressed patients.

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1573-6903

SHR ; ADHD ; reinforcement ; nucleus accumbens ; α2-adrenoceptor ; dopamine release ; monoamines

Springer Online Journal Archives 1860-2000

Medicine

Abstract The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attentiondeficit disorder (ADHD). The behavioural problems have been suggested to be secondary to altered reinforcement mechanisms in which nucleus accumbens dopaminergic activity plays an important role. Interaction between the noradrenergic and dopaminergic system in the nucleus accumbens has been implicated in the locomotor hyperactivity and impaire discriminative performance of SHR. The present study therefore investigated whether there was any change in the α2-adrenoceptor mediated inhibition of dopamine release from nucleus accumbens slices of SHR in comparison with their normotensive Wistar-Kyoto (WKY) controls. The electrically stimulated release of [3H]dopamine (DA) from nucleus accumbens slices was decreased to a similar extent by UK14,304, an α2-adrenoceptor agonist, in SHR and WKY. Basal norepinephrine (NE) levels were increased in locus coeruleus (LC) and A2 noradrenergic nuclei, but not in the A1 nucleus of SHR, while basal serotonin (5-HT) levels were increased in all these pons-medulla nuclei. These results suggest that a primarily dysfunctional LC and A2 nucleus does not have a secondary effect on dopaminergic transmission in the nucleus accumbens via α2-adrenoceptor mediated inhibition of DA release. Basal monoamine levels in several brain areas of SHR were significantly different from that of WKY. DA, and 5-HT turnover were decreased in SHR versus WKY suggesting hypofunctional dopaminergic and serotonergic systems in some brain areas of SHR.

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1573-6903

Frontal cortex ; desipramine ; gamma-aminobutyric acidB receptors

Springer Online Journal Archives 1860-2000

Medicine

Abstract The aim of the present study was to investigate whether a disturbance of the central noradrenergic (NA) system could cause changes in gamma-aminobutyric acidB (GABAB) receptors in the rat frontal cortex. Manipulation of the NA projection to the frontal cortex was achieved by bilateral lesion of the locus coeruleus with 6-hydroxydopamine (6-OHDA) or chronic treatment with the NA reuptake blocker and antidepressant drug, desipramine. Precautions were taken to ensure that the GABAB receptor assay was performed optimally and was not confounded by the presence of endogenously generated GABA. The results show conclusively that manipulation of the NA projection did not result in any significant change in the number (Bmax) or affinity (Kd) of GABAB receptors in the frontal cortex. These results do not support the hypothesis that hypoactivity of the central NA system can lead to changes in cortical GABAB receptors and that antidepressant drugs act by increasing GABAB receptor binding in the frontal cortex.

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1573-6903

Springer Online Journal Archives 1860-2000

Medicine

Abstract The effects of δ-aminolaevulinic acid (ALA), porphobilinogen (PBG), γ-aminobutyric acid (GABA), muscimol, glutamic acid and kainic acid on [3H]2-deoxy-d-glucose uptake by cultured neurons were investigated. Exposure of the cultures for 4 days, to ALA at concentrations as low as 10 μM caused a significant, dose-dependent decrease in [3H]2-deoxy-d-glucose uptake. Neither ALA nor PBG appeared to interfere directly with glucose transport into the neuron but 1 mM ALA caused an initial stimulation of [3H]2-deoxy-d-glucose uptake which increased to a maximum after 4 hr and fell to below control values after 19 hr exposure. GABA and muscimol caused similar increases in [3H]2-deoxy-d-glucose uptake but these values remained above control levels after 19 hr exposure. Glutamic acid and kainic acid caused an immediate increase in [3H]2-deoxy-d-glucose uptake which declined to mininum values after 4 hr exposure. The effect of ALA on glucose utilization in neurons may be of particular relevance to patients with acute porphyria where a genetic lesion in neural haem and haemoprotein biosynthesis is postulated to occur. ALA appeared to be more toxic to the neurons than any of the other compounds tested, possibly causing a critical depletion of energy reserves and cell death.

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