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U Ungerstedt

Publications and source records attributed to U Ungerstedt.

At least 19 recordsLinked to original sources
PubMed1992

Immunohistochemical evidence for a crossed cholecystokinin corticostriatal pathway in the rat.

Using the indirect immunofluorescence technique, the effects of decortication and callosotomy on the pattern of cholecystokinin (CCK)-like immunoreactivity were studied in the striatum of the rat. Decortication plus callosotomy, but not decortication alone, caused a strong decrease in the immunoreactivity on the side ipsilateral to the lesion. An almost complete disappearance of CCK immunoreactive patches in the medial-dorsal aspects of the striatum was observed. These results indicate that part of the striatal CCK immunoreactive fibres are of cortical origin, to a considerable extent from the contralateral side.

Animals↗
PubMed1992

Effect of the neurotoxin AF64A on intrinsic and extrinsic neuronal systems of rat neostriatum measured by in vivo microdialysis.

In the present in vivo microdialysis study the aziridinium ion of ethylcholine mustard, AF64A and the excitotoxin ibotenic acid were compared for their effects on extracellular striatal acetylcholine, choline, gamma-aminobutyric acid (GABA), dopamine and its metabolites, glutamate and aspartate, measured in the same perfusate sample, under basal and high KCL conditions. Ten days following unilateral striatal injections of AF64A (2 x 0.08 to 2 x 8 mM) there was a dose-dependent decrease in the extracellular striatal levels of acetylcholine and GABA, the two major intrinsic striatal neurotransmitter systems. No significant effects were observed on any of the monitored neurotransmitter systems following the lowest (2 x 0.08 mM) dose of AF64A, while at the intermediate (2 x 0.8 mM) dose, AF64A produced a unilateral > 50% and > 70% decrease in basal extracellular striatal acetylcholine and GABA levels respectively. The effects of K(+)-depolarization on extracellular acetylcholine and GABA levels were diminished by approximately 50%. At the highest dose (2 x 8 mM), extracellular striatal acetylcholine levels were non-detectable under basal conditions, while the GABA levels were decreased by > 50%, when compared with the contralateral intact side. However, at this dose, GABA levels were bilaterally decreased compared to levels observed in control animals. Basal extracellular striatal dopamine and glutamate levels, representing the two major extrinsic neurotransmitter systems innervating the neostriatum were only affected by the highest dose of AF64A. The excitotoxin ibotenic acid (2 x 28.4 mM) produced a strong unilateral decrease in extracellular striatal acetylcholine (> 80%) and GABA (> 90%) levels, without significantly affecting basal dopamine and glutamate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Evidence for a substrate of neuronal plasticity based on pre- and postsynaptic neurotensin-dopamine receptor interactions in the neostriatum.

The major mechanism underlying the neuroleptic action of the tridecapeptide neurotensin (NT) appears to be an interaction with dopamine receptor mechanisms based on biochemical binding and behavioral experiments. In vivo microdialysis was used in conscious rats to investigate the effects of local perfusion with NT on the sensitivity of striatal dopamine D1 and D2 receptors for their selective agonists by monitoring extracellular dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and gamma-aminobutyric acid levels in the awake unrestrained male rat. Perfusion with NT (10 nM) counteracted the inhibitory effects of the dopamine D2 agonist pergolide (500 nM) on extracellular levels of dopamine and gamma-aminobutyric acid. In contrast, NT (10 mM) significantly enhanced the reduction of extracellular striatal levels of dopamine after perfusion with the D1 agonist SKF 38393 (5 microM), and this combined treatment also resulted in a significant increase in the extracellular striatal levels of gamma-aminobutyric acid. These results provide in vivo evidence that NT regulates central dopamine transmission by reducing pre-and postsynaptic dopamine D2 and enhancing D1 receptor sensitivity possibly through an antagonistic NT receptor-D2 receptor interaction. This heteroregulation has the potential to substantially increase the plasticity within the dopamine synapse.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Seizure related elevations of extracellular amino acids in human focal epilepsy.

Intracerebral microdialysis combined with electrocorticographic recordings was used in a patient subjected to epilepsy surgery. The patient developed a series of partial seizures during an 8 min period. Marked elevations of aspartate (79-fold), glycine (21-fold), glutamate (16-fold) and serine (8-fold) dialysate concentrations occurred in association with onset of the period with seizures. Recurrent seizures occurred, in spite of normalizing amino acid levels. Other amino acids analyzed (aspargine, threonine, arginine, alanine, taurine, tyrosine, phenylalanine, isoleucine and leucine) showed less pronounced changes (1-5 times the basal levels).

Amino Acids↗
PubMed1992

Amphetamine regulation of mesolimbic dopamine/cholecystokinin neurotransmission.

The effects of acute and repeated amphetamine administration on mesolimbic dopamine (DA) neurons was assessed by studying DA and cholecystokinin (CCK) release in the nucleus accumbens (Acc), as well as effects on mRNA genes regulating DA and CCK synthesis in ventral tegmental area (VTA) cells in rats. Amphetamine (1.5 mg/kg) markedly increased extracellular levels of DA in the medial Acc (assessed by in vivo microdialysis) in drug-naive animals, about twice the amount released in animals repeatedly administered the drug for the previous 7 days (twice daily). CCK overflow was found to mirror the DA responses in that the very transient elevation of CCK monitored in drug-naive animals was attenuated in those with prior amphetamine use. The attenuation of both DA and CCK overflow in the medial Acc was found to be associated with a decrease in the number of CCK mRNA-positive VTA neurons (assessed by in situ hybridization histochemistry). Although the number of cells expressing CCK mRNA were decreased, the gene expression in those positive CCK and tyrosine hydroxylase mRNA cells in the VTA was significantly increased. The CCK mRNA neurons in the VTA were positively identified as those projecting to the medial Acc by the local perfusion of Fluoro-gold retrograde tracer via microdialysis probes located in the Acc.

Amphetamine↗
PubMed1992

Effects of nerve growth factor on cortical and striatal acetylcholine and dopamine release in rats with cortical devascularizing lesions.

The effects of intraventricular nerve growth factor (NGF) or saline treatments on extracellular acetylcholine (ACh), dopamine (DA) and adenosine (Ade) levels in the cortex and striatum of rats with unilateral devascularizing cortical lesions were studied in vivo with microdialysis. The devascularizing cortical lesion produced a decrease in extracellular ACh levels in both cortex and striatum as compared to those in normal rats, while the NGF treatment produced a significant increase in ACh levels in both regions. NGF could even increase cortical ACh levels in normal rats. The cortical lesion produced a decrease in extracellular DA in the cortex, while the NGF treatment appeared to reverse this effect. No significant changes in DA were observed in the striatum. The present study gives evidence that a unilateral cortical devascularizing lesion leads to changes in extracellular ACh and DA levels in cortex and striatum and that these changes could be reversed with intraventricular NGF treatment.

Acetylcholine↗
PubMed1992

Amphetamine enhances extracellular concentrations of dopamine and acetylcholine in dorsolateral striatum and nucleus accumbens of freely moving rats.

The effect of two consecutive administrations of amphetamine (1.5 mg/kg, s.c.; 2 h apart) on dopamine (DA) and acetylcholine (ACh) efflux in dorsolateral striatum and nucleus accumbens was studied with in vivo microdialysis in freely moving rats. Amphetamine was found to cause a more persistent increase of extracellular DA in the dorsolateral striatum than in the nucleus accumbens. The increase in DA overflow by amphetamine was accompanied by an increase of extracellular ACh in both brain areas. The results are inconsistent with the hypothesis of an amphetamine-induced inhibitory regulation by DA on ACh overflow.

Acetylcholine↗
PubMed1992

Regulation of kynurenic acid synthesis studied by microdialysis in the dorsal hippocampus of unanesthetized rats.

The production of the broad spectrum excitatory amino acid receptor antagonist kynurenic acid was assessed by hippocampal microdialysis in freely moving rats. Extracellular kynurenic acid, determined spectrophotometrically, was measured following the perfusion of its bioprecursor L-kynurenine (500 microM) through the dialysis probe. In this paradigm, the concentration of kynurenic acid reached plateau levels within 2 h. These steady state levels were more than doubled in gliotic quinolinate-lesioned tissue. The non-specific inhibitor of kynurenine aminotransferase, aminooxyacetic acid (300 microM), and the depolarizing agent veratridine (50 microM), introduced through the dialysis membrane, caused a 69 and 57% decrease, respectively, in extracellular kynurenic acid. The effect of veratridine was rapidly reversible and was blocked by 5 microM tetrodotoxin or in the quinolinate-lesioned hippocampus. In contrast, the effect of aminooxyacetic acid was longer lasting upon drug discontinuation, and was not reversed by tetrodotoxin or in lesioned tissue. These data demonstrate that hippocampal kynurenic acid can be regulated by direct interference with its biosynthetic enzyme and by a distinct process involving neuron-glia interactions.

Aminooxyacetic Acid↗
PubMed1992

The effects of neurotensin on GABA and acetylcholine release in the dorsal striatum of the rat: an in vivo microdialysis study.

The effects of local perfusion with the tridecapeptide neurotensin (NT) on endogenous gamma-aminobutyric acid (GABA), acetylcholine (ACh) and choline release in the dorsal neostriatum were monitored using in vivo microdialysis in the halothane anaesthetized rat. The results show that NT (10 and 1000 nM) differentially regulates striatal GABA release without significantly influencing the release of either striatal ACh or choline. NT increased striatal GABA release both in the absence and presence of the ACh esterase inhibitor neostigmine (neo; 10 microM) in the perfusion medium. However, both basal GABA levels and responsitivity to NT were elevated in the presence of neo. The NT induced increase in striatal GABA release was reversed by the addition of tetrodotoxin (TTX; 1 micron) to the perfusion medium. These data suggest that (1) NT may play a role in modulating GABAergic neurotransmission in the dorsal neostriatum and (2) that the increase in GABA release may occur independently of an increase in the cholinergic component in the dorsal neostriatum, possibly via high affinity NT receptors located on striatal GABAergic neurons.

Acetylcholine↗
PubMed1992

Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors.

The effects of insulin, and its interactions with catecholamines through beta-adrenoceptors, on human adipose tissue glucose utilization and lipolysis were investigated in vivo. Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was performed in healthy subjects of normal weight, before and during a 2-h hyperinsulinaemic (61 +/- 3 mU/l), euglycaemic clamp. The tissue was perfused with or without the beta-adrenergic agonist isoproterenol (10(-6) mol/l), and the tissue dialysate concentrations of glucose, glycerol (lipolysis index) lactate and pyruvate were determined. During the insulin infusion, glucose in adipose tissue decreased by 20% (p less than 0.001), despite arterial steady-state normoglycaemia. The concentrations of lactate and pyruvate increased gradually to a steady-state plateau of twice the basal level in adipose tissue and arterial blood. Insulin-induced suppression of glycerol (lipolysis index) was, if anything, more marked in adipose tissue than in plasma (65% vs 50% decrease from baseline levels, p less than 0.05). In situ perfusion of adipose tissue with isoproterenol, starting either at the beginning of the study period or at 45 min after initiation of the insulin infusion, resulted in marked and rapid elevations of all the investigated metabolites in the adipose tissue extracellular compartment (p less than 0.05-0.005). It is concluded that insulin action on glucose uptake and lipolysis in human adipose tissue in vivo is counteracted by beta-adrenoceptor stimulation. In contrast, insulin and beta-adrenoceptors have synergistic effects on non-oxidative glucose metabolism in human adipose tissue in situ.

Adipose Tissue↗
PubMed1992

Microdialysis measurement of the absolute glucose concentration in subcutaneous adipose tissue allowing glucose monitoring in diabetic patients.

The possibility of continuously monitoring the absolute glucose concentration in subcutaneous adipose tissue, using microdialysis of the extracellular water space, was investigated in six Type 1 (insulin-dependent) diabetic patients. By using a large microdialysis probe (30 x 0.62 mm), and by perfusing with a low flow rate (0.5 microliters/min), complete recovery of glucose was attained in vitro. In the patients the dialysis probe was implanted subcutaneously, perfused by a wearable microinfusion pump, and dialysate samples were collected in 60-min fractions over 10 h. The absolute glucose concentration in the tissue dialysate was the same or almost the same as the blood glucose concentration (range 87-101% of the blood glucose value). The changes in blood glucose were closely paralleled by the variations in adipose tissue glucose (r = 0.93, p < 0.01), and the recovery of glucose in the microdialysate remained constant during the 10-h study period. In conclusion, it is possible, using microdialysis, to directly determine the absolute glucose concentration in subcutaneous adipose tissue. Hence, this technique may be used for continuous glucose monitoring in diabetic patients.

Adipose Tissue↗
PubMed1992

Treatment of malignant glioma by a new therapeutic principle.

L-2, 4 diaminobutyric acid (DAB) is a non-physiological, cationic amino acid transported into cells by System A with potent antitumour activity in vitro against human glioma cells. This activity was the result of the pronounced concentrated uptake of DAB in glioma cells to the extent that a cellular lysis could occur due to osmotic reasons. We describe the treatment of 3 patients with inoperable malignant glioma by direct and continuous administration of DAB in tumour tissue employing a microdialysis technique. One to three microdialysis probes were implanted in the tumour tissue through small dural incisions in 3 patients with inoperable malignant glioma. Micropumps charged with 3 ml a day of a Tris-buffered 0.125 M DAB solution made isotonic at pH 7.55 were adapted to the input channel of the probe and a sampling tube to the output for continuous flowing into tumour tissue. The patients were treated in this way for a total of 14-21 days without side effects assignable to DAB. Massive tumour necrosis occurred as judged by comparison of computed tomography performed before and after DAB treatment. The yield of the dialysis procedure with regard to DAB was estimated to be 40-50%. The dialysate concentration of arginine (a cationic amino acid considered to be transported mainly by system A) was high and increased nearly 4-fold from day 3 to day 6 of treatment. DAB administered in this way into malignant brain tumour tissue was well tolerated and showed promising antitumour activity in the 3 patients with inoperable malignant glioma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminobutyrates↗
PubMed1992

Involvement of local ischemia in endothelin-1 induced lesions of the neostriatum of the anaesthetized rat.

The present study examines the possibility that lesions induced by intrastriatal injections of endothelin-1 (ET-1, 0.43 nmol/0.5 microliter) are ischemic in nature due to a vasoconstriction of the cerebral microvessels. In time course and dose-response experiments with ET-1 and in comparisons with ET-3, the volume of the lesions has been determined based mainly on the disappearance of striatal nerve cells, using a computer assisted morphometrical analysis. The blood flow in the neostriatum close to the site of injection of ET-1 was determined acutely by Laser-Doppler flowmetry. The acute metabolic effects of ET-1 were also studied on striatal superfusate levels of lactate, pyruvate, dopamine and its metabolites DOPAC (3,4-dihydroxyphenylacetic acid) and homovanillic acid (HVA) using an intrastriatal microdialysis probe. Dose related striatal lesions were observed with ET-1 (0.043-0.43 nmol) with a peak lesion volume after 24-48 h and the possible existence of a penumbra area. ET-3 showed a reduced potency to produce striatal lesions compared to ET-1. The lesions induced by ET-1 were prevented by coinjection with dihydralazine, a vasodilator drug. Acutely ET-1 (0.43 nmol/0.5 microliter) produced a prolonged reduction of the cerebral blood flow down to 40% of control values and temporary increases of striatal lactate and DA efflux, the latter change being very marked. Also a significant reduction of DOPAC and HVA was observed. These neurochemical changes were all prevented by treatment with dihydralazine.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Amphetamine regulation of acetylcholine and gamma-aminobutyric acid in nucleus accumbens.

In situ hybridization histochemistry and in vivo microdialysis were combined to study the effect of amphetamine on the expression of choline acetyltransferase and glutamate decarboxylase67 mRNA and in vivo release of acetylcholine and GABA in rat medial nucleus accumbens. Differential effects on acetylcholine and GABA neurons by a single challenge injection of amphetamine (1.5 mg/kg, s.c.) were apparent in saline-pretreated and amphetamine-pretreated (same dose, twice daily for the previous seven days) rats. Extracellular acetylcholine levels were increased up to 50% over a prolonged period following both single and repeated amphetamine. In contrast, extracellular concentrations of GABA were gradually decreased to half the control values, but only in rats receiving repeated amphetamine. Although the increase of acetylcholine release was not associated with any change in choline acetyltransferase mRNA levels, the number of neurons expressing high levels of glutamate decarboxylase67 mRNA was decreased (28%) following repeated injections. Thus we suggest that amphetamine decreases extracellular GABA levels by a slow mechanism, associated with the decreased expression of glutamate decarboxylase67 mRNA in a subpopulation of densely labeled neurons in the medial nucleus accumbens. The delayed response by GABA to amphetamine may reflect supersensitivity in the activity of postsynaptic gamma-aminobutyric acid-containing neurons in nucleus accumbens as a consequence of the repeated amphetamine treatment.

Acetylcholine↗
PubMed1992

Intracerebral microdialysis of extracellular amino acids in the human epileptic focus.

Extracellular levels of aspartate (ASP), glutamate (GLU), serine (SER), asparagine (ASN), glycine (GLY), threonine (THR), arginine (ARG), alanine (ALA), taurine (TAU), tyrosine (TYR), phenylalanine (PHE), isoleucine (ILEU), and leucine (LEU) were monitored by using intracerebral microdialysis in seven patients with medically intractable epilepsy, undergoing epilepsy surgery. In association with focal seizures, dramatic increases of the extracellular ASP, GLU, GLY, and SER concentrations were observed. The other amino acids analyzed, including TAU, showed small changes. The results support the hypothesis that ASP, GLU, GLY, and possibly SER, play an important role in the mechanism of seizure activity and seizure-related brain damage in the human epileptic focus.

Adolescent↗
PubMed1992

Cholecystokinin is released from a crossed corticostriatal pathway.

The release of striatal cholecystokinin, glutamate, aspartate and dopamine was studied in vivo with microdialysis in decorticated rats, with or without callosotomy. Unlesioned rats were also analysed. Unilateral decortication produced a unilateral decrease in K(+)-stimulated extracellular striatal glutamate and aspartate levels, without decreasing cholecystokinin or dopamine levels. However, following decortication plus callosotomy, basal and K(+)-stimulated extracellular cholecystokinin and glutamate levels were significantly decreased in the striatum ipsilateral to side of decortication. Aspartate levels were bilaterally decreased. These results give evidence for the existence of crossed corticostriatal projections containing releasable cholecystokinin and glutamate.

Animals↗