PubMed Health⌕ Search

Biomedical subjects

M Herrera-Marschitz

Publications and source records attributed to M Herrera-Marschitz.

At least 73 records · Page 4Linked to original sources
PubMed1994

Long-term effects of perinatal asphyxia on basal ganglia neurotransmitter systems studied with microdialysis in rat.

Asphyxia was induced in pups delivered by caesarean section on pregnant Sprague-Dawley rats. Rats within the last day of gestation were anaesthetised and hysterectomized. The uterus horns including the foetuses were placed in a water bath for various periods of time. Following asphyxia the uterus horns were opened. The pups were removed, stimulated to breathe, left to recover and given to surrogate mothers. Control and asphyctic pups were obtained from each mother. Rats surviving asphyctic periods longer than 20 min at 37 degrees C showed chronic deficits in the release of neurotransmitters monitored with microdialysis in the basal ganglia. The main change observed in 6-month-old male rats that underwent severe perinatal asphyxia was a marked decrease in striatal dopamine release, monitored under basal and D-amphetamine stimulated conditions, as compared with control (normal- or caesarean-delivered) rats. Striatal glutamate and aspartate levels were also decreased following asphyxia. In the substantia nigra, the main effect of asphyxia was a decrease of both gamma-aminobutyric acid (GABA) and aspartate levels. Thus, this study provides evidence that perinatal asphyxia leads to chronic deficits in neurotransmission in the basal ganglia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Cholecystokinin in cortico-striatal neurons in the rat: immunohistochemical studies at the light and electron microscopical level.

Using immunohistochemical techniques we have analysed the occurrence of cholecystokinin-like immunoreactivity (CCK-LI) in the cortex and striatum of the rat. In the cortex few CCK-immunoreactive cell bodies, mainly interneurons, could be visualized in normal brains, and a moderately dense network of CCK fibres was also observed. Injections of colchicine into the striatum led to an accumulation, in the surrounding cortex, of CCK-LI in the initial segment of the axon of numerous cells. In addition, with an antibody to pro-CCK several cell bodies, many of which with pyramidal shape, could be visualized. Furthermore, retrograde staining of cortical cells after unilateral injection of wheat germ agglutinin into the striatum revealed bilaterally in the cortex a number of labelled cells that also contained pro-CCK-LI. In the striatum CCK-LI was diffusely distributed in fine fibres as well as in patches of fibres located in the medial aspects. After decortication followed by callosotomy these patches disappeared on the side ipsilateral to the lesion, while the pattern of immunoreactivity of several other peptides in the striatum was unaffected. No change was observed on the contralateral side. Decortication or callosotomy alone did not affect the pattern of CCK-LI. At the ultrastructural level several CCK-immunoreactive terminals could be observed, mostly with clear, densely packed vesicles and straight asymmetric synaptic contacts with small spines, characteristic for terminals of cortical origin. The results are consistent with the presence of a major, partly crossed, CCK-containing cortico-striatal pathway.

Animals↗
PubMed1994

Unilateral neonatal intracerebroventricular 6-hydroxydopamine administration in rats: I. Effects on spontaneous and drug-induced rotational behaviour and on postmortem monoamine levels.

6-Hydroxydopamine (6-OHDA; 100 micrograms in 5 microliters) was injected into the right ventricle (intracerebroventricular, ICV) of 3-day old Sprague-Dawley rats in an attempt to produce a unilateral neonatal dopamine (DA) lesion. At adult stage, the rats were studied for spontaneous, handling- and drug-induced rotational behaviour. The 6-OHDA-treated rats showed hyperreactivity at handling, in the animal facility and in the experimental sets. This behaviour was not observed in vehicle-treated rats, and it did not decrease through the successive experiments. Apomorphine (0.05-1 mg/kg, SC) and caffeine (20 mg/kg SC) produced contralateral rotation in neonatal 6-OHDA, but not in vehicle-injected rats. d-Amphetamine (0.2-2 mg/kg, SC) produced strong, dose-dependent, ipsilateral rotation, while the serotonin (5-HT) releasing agent, p-chloroamphetamine (2 mg/kg, SC) produced a short-lasting and weak ipsilateral rotation in the 6-OHDA-treated rats. On the 6-OHDA-injected side, DA and metabolites levels were reduced by > 70-90% in the striatum, the nucleus accumbens and the tuberculum olfactorium, while in the mesencephalon a 50% decrease was found. On the contralateral side, restricted decreases in DA and metabolites were observed. Noradrenaline (NA) levels were decreased bilaterally in the forebrain. In contrast, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were increased in the ipsilateral striatum (> 180%), and tuberculum olfactorium (> 120%). Thus, neonatal unilateral ICV 6-OHDA administration produced a significant unilateral decrease in tissue levels of DA and metabolites, which was most marked in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Unilateral neonatal intracerebroventricular 6-hydroxydopamine administration in rats: II. Effects on extracellular monoamine, acetylcholine and adenosine levels monitored with in vivo microdialysis.

6-hydroxydopamine (6-OHDA, 100 micrograms in 5 microliters) was injected into the right ventricle of 3-day-old Sprague-Dawley rats in order to produce a unilateral dopamine (DA) lesion. At adult stage, the rats were implanted with microdialysis probes into the left and right striata. On the injected side, basal extracellular levels of DA were reduced by > 65%, as compared to the contralateral side or to the levels found in vehicle-injected rats. Extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were reduced by > 95%, while acetylcholine (ACh) was decreased by > 50%. d-Amphetamine (2 mg/kg SC) produced a 10-fold increase in extracellular DA levels in the striatum contralateral to the 6-OHDA-injected side, while on the ipsilateral side. DA levels were not affected by d-amphetamine. d-Amphetamine produced an increase (> 2 fold) in extracellular ACh levels, on both ipsilateral and contralateral sides. Choline and adenosine levels were unaffected by any of the experimental conditions. Thus, neonatal unilateral ICV administration of 6-OHDA produced an ipsilateral decrease in striatal extracellular DA, DOPAC and HVA levels, compared to the contralateral side. A reduction of extracellular ACh levels was also observed on the 6-OHDA-injected side. The DA releasing effect of d-amphetamine was abolished on the 6-OHDA-injected side, but not that on ACh levels, indicating that striatal DA and ACh d-amphetamine-induced release are produced by independent mechanisms in the neonatally unilateral 6-OHDA-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Expression of mRNAs encoding dopamine receptors in striatal regions is differentially regulated by midbrain and hippocampal neurons.

The glutamate analogue kainic acid was injected into the hippocampus of intact or 6-hydroxydopamine deafferented rats to investigate the influence of hippocampal neurons on the expression of dopamine D1 and D2 receptor mRNAs in subregions of the striatal complex and possible modulation by dopaminergic neurons. Quantitative in situ hybridization using 35S-labeled oligonucleotide probes specific for dopamine D1 and D2 receptor mRNAs, respectively, were used. It was found that an injection of kainic acid into the hippocampal formation had alone no significant effect on dopamine D1 or D2 receptor mRNA levels in any of the analyzed striatal subregions in animals analyzed 4 h after the injections. Kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion produced an increase in D1 receptor mRNA levels in the ipsilateral medial caudate-putamen, and a bilateral increase in core and shell of nucleus accumbens (ventral striatal limbic regions). A unilateral 6-hydroxydopamine lesion alone caused an increase in D2 receptor mRNA in the lateral caudate-putamen (dorsal striatal motor region) ipsilateral to the lesion and an increase in D1 receptor mRNA in the accumbens core ipsilateral to the lesion. However, in dopamine-lesioned animals, dopamine D1 receptor mRNA levels were increased bilaterally in nucleus accumbens core and shell and in the ipsilateral medial caudate-putamen following kainic acid stimulation in the hippocampus ipsilateral to the dopamine lesion. These results indicate a differential regulation of the expression of dopamine D1 and D2 receptor mRNAs by midbrain and hippocampal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The striatonigral dynorphin pathway of the rat studied with in vivo microdialysis--I. Effects of K(+)-depolarization, lesions and peptidase inhibition.

Extracellular levels of dynorphin B were analysed with in vivo microdialysis in the neostriatum and substantia nigra of halothane-anaesthetized rats. Dopamine and its metabolites, 3,4-dihydroxyphenyl-acetic acid and homovanillic acid, as well as GABA were simultaneously monitored. Chromatographic analysis revealed that the dynorphin B-like immunoreactivity measured in perfusates collected under basal and K(+)-depolarizing conditions co-eluted with synthetic dynorphin B. Dynorphin B, GABA and dopamine levels were Ca(2+)-dependently increased by K(+)-depolarization, while 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were decreased. Dopamine and its metabolites, but not dynorphin B or GABA levels, were significantly decreased after a unilateral 6-hydroxydopamine injection into the left medial forebrain bundle. In contrast, following a unilateral injection of ibotenic acid into the striatum, dynorphin B and GABA levels were decreased by > 50% in striatum and substantia nigra on the lesioned side, whereas no significant changes were observed in basal dopamine levels. The inclusion of the peptidase inhibitor captopril (50-500 microM) into the nigral perfusion medium produced a concentration-dependent increase in nigral extracellular levels of dynorphin B. In the striatum, a delayed increase in dynorphin B and GABA levels could be observed following the nigral captopril administration, but this effect was not concentration-dependent. Thus, we demonstrate that extracellular levels of dynorphin B, dopamine and GABA can simultaneously be monitored with in vivo microdialysis. Extracellular dynorphin B appears to originate from neurons, since the levels were (i) increased in a Ca(2+)-dependent manner by K(+)-depolarization, and (ii) decreased by a selective lesion of the striatum, known to contain cell bodies of dynorphin neurons in the striatonigral pathway. Furthermore, (iii) the increase in nigral dynorphin B levels by peptidase inhibition suggests the presence of clearance mechanisms for the released dynorphin peptides.

Animals↗
PubMed1994

The striatonigral dynorphin pathway of the rat studied with in vivo microdialysis--II. Effects of dopamine D1 and D2 receptor agonists.

In vivo microdialysis was used to study the effect of intracerebral administration of dopamine agonists on dynorphin B release in the striatum and substantia nigra of rats. The release of dopamine and GABA was also investigated. Administration of the dopamine D1 agonist SKF 38393 (10-100 microM) into the striatum increased extracellular dynorphin B and GABA levels in the ipsilateral substantia nigra, in a concentration-dependent manner. After a short-lasting increase, nigral dopamine levels were significantly decreased after the highest concentration of striatal SKF 38393. An increase in striatal dynorphin B, GABA and dopamine levels was also observed. When SKF 38393 (10 microM) was administered into the substantia nigra, nigral dynorphin B and GABA, but not dopamine levels increased. No significant effects were observed on striatal levels. Administration of the dopamine D2 agonist, quinpirole (100 microM), into the striatum decreased dopamine levels in both striatum and substantia nigra, while no effect was observed on striatal or nigral dynorphin B and GABA levels. Quinpirole (10-100 microM) given into the substantia nigra, decreased striatal dopamine levels in a concentration manner. In the nigra, a short-lasting increase in dopamine levels was observed following the highest concentration of nigral quinpirole (100 microM). The effect was followed by a decrease in dopamine levels. No significant effects were observed on striatal or nigral dynorphin B and GABA levels. The results show that stimulation of D1 receptors in striatum and substantia nigra leads to activation of the striatonigral dynorphin pathway. A parallel effect could also be seen on nigral GABA release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

On the origin of striatal cholecystokinin release: studies with in vivo microdialysis.

In the present study, extracellular levels of the neuropeptide cholecystokinin (CCK), of the monoamine dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and of the excitatory amino acids glutamate and aspartate were simultaneously monitored by microdialysis in the neostriatum of halothane-anesthetized rats under basal and K(+)-depolarizing conditions. Extracellular CCK and dopamine levels, but not glutamate and aspartate levels, were decreased by perfusion with a Ca(2+)-free medium, under both basal and K(+)-depolarizing conditions. HPLC revealed that the majority of the CCK-like immunoreactivity in the perfusates coeluted with CCK octapeptide. Striatal extracellular CCK levels were decreased by decortication plus callosotomy, with a parallel decrease in glutamate levels. Striatal extracellular levels of dopamine, DOPAC, and HVA were significantly decreased in animals treated previously with a unilateral 6-hydroxydopamine injection into the medial forebrain bundle. In these animals, however, the effect of decortication plus callosotomy on CCK and glutamate levels was not further augmented. Thus, this study supports the hypothesis of a neuronal origin of extracellular CCK and dopamine monitored with microdialysis in the striatum of the rat, and also supports the idea of a partly contralateral origin of corticostriatal CCK and glutamate inputs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Differential regulation of preprotachykinin-A mRNA expression in striatum by excitation of hippocampal neurons.

In this report we have studied the influence of hippocampal neurons on neuropeptide mRNA expression in both dorsal and ventral striatum in the rat. Intrahippocampal unilateral kainic acid injections were performed in control animals and in animals with a unilateral 6-hydroxydopamine-induced dopamine deafferentation of the striatum. In situ hybridization combined with quantitative image analysis was used to study the expression of preprotachykinin A mRNA encoding the neuropeptides substance P and neurokinin A. The 6-hydroxydopamine-induced lesion caused a decrease of preprotachykinin A mRNA levels in the ipsilateral dorsal striatum and in both sides of the ventral striatum. In normal rats, the intrahippocampal kainic acid injection caused a twofold increase in preprotachykinin A mRNA in the limbic parts of the striatum, which are innervated by the hippocampus. No effect of the kainic acid injection was seen in the lateral parts of the dorsal striatum, a region which does not appear to be innervated by the hippocampus. Animals with a 6-hydroxydopamine lesion showed a similar kainic acid-mediated increase in preprotachykinin A mRNA in parts of the ventral striatum. In the dopamine-lesioned dorsal striatum and ventral striatum the decreased preprotachykinin A mRNA levels were normalized by the intrahippocampal kainic acid injection. These results show that kainic acid-mediated excitation of hippocampal neurons causes a dopamine-independent induction of preprotachykinin A mRNA expression in parts of the ventral striatum, and reverses the dopamine deafferentation-induced decrease of preprotachykinin A mRNA in both dorsal and ventral striatum. Combined, our results suggest that hippocampal neurons can regulate preprotachykinin A mRNA expression in both the ventral and the dorsal striatum.

Animals↗
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

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

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↗
PubMed1991

Chronic nicotine treatment counteracts the decrease in extracellular neostriatal dopamine induced by a unilateral transection at the mesodiencephalic junction in rats: a microdialysis study.

The effect of chronic treatment with (-)-nicotine on the decrease in extracellular dopamine (DA) levels in neostriatum induced by a unilateral transection at the meso-diencephalic junction in rats was studied. At the lesion time, Alzet minipumps filled with (-)-nicotine were implanted subcutaneously. Two weeks later, microdialysis probes were implanted bilaterally into the neostriatum. Perfusates were assayed for DA, acetylcholine (ACh) and metabolites in HPLC systems under basal and KCl stimulated conditions. The unilateral hemitransection produced an ipsilateral decrease in neostriatal extracellular DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), but not in ACh levels. Chronic nicotine treatment counteracted the lesion-induced decrease in DA, but had no effect on extracellular DA levels in the contralateral neostriatum or in normal rats. The results support the idea that chronic nicotine treatment may protect against degeneration of central DA neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Short-term dopaminergic regulation of GABA release in dopamine deafferented caudate-putamen is not directly associated with glutamic acid decarboxylase gene expression.

In vivo microdialysis and in situ hybridization were combined to study dopaminergic regulation of gamma-amino butyric acid (GABA) neurons in rat caudate-putamen (CPu). Potassium-stimulated GABA release in CPu was elevated following a dopamine deafferentation. Local perfusion with exogenous dopamine (50 microM) for 3 h via the microdialysis probe attenuated the potassium-stimulated increase in extracellular GABA in CPu. Expression of glutamic acid decarboxylase (GAD) mRNA was also increased in the dopamine deafferented CPu. However, local perfusion with dopamine had no significant attenuating effect on the increased GAD mRNA expression. These findings indicate that dopaminergic regulation of GABA neurons in the dopamine deafferented CPu includes both a short-term effect at the level of GABA release independent of changes in GAD mRNA expression and a long-term modulation at the level of GAD gene expression.

Afferent Pathways↗
PubMed1991

Postsynaptic dopamine/adenosine interaction: I. Adenosine analogues inhibit dopamine D2-mediated behaviour in short-term reserpinized mice.

Mice pretreated with reserpine 5 mg/kg (4 h prior to the start of motor activity recording) showed locomotor activation after the administration of the D-2 agonist bromocriptine (5 mg/kg). This bromocriptine-induced locomotor activity was dose dependently inhibited by the co-administration of a D-2 antagonist (sulpiride) and dose dependently potentiated by a D-1 agonist (CY 208-243). The potentiating effect of the D-1 agonist could be inhibited by either a D-1 or a D-2 antagonist (SCH 23390 1 mg/kg or sulpiride 100 mg/kg, respectively). The bromocriptine-induced locomotor activity was not altered by either blockade of D-1 dopaminergic receptors (SCH 23390 1 mg/kg) or by co-administration of a greater dose of reserpine (10 mg/kg) plus the dopamine synthesis inhibitor, alpha-methyl-p-tyrosine (200 mg/kg). The adenosine agonists, L-PIA (a preferentially A-1 adenosine agonist) and NECA (an A-1 and A-2 adenosine agonist with above 10-fold greater affinity for A-2 than L-PIA) inhibited in a dose-dependent manner the effect of bromocriptine, NECA being above ten times more potent than L-PIA. The findings show that bromocriptine stimulates postsynaptic D-2 receptors in dopamine-depleted mice and that this effect can be inhibited by adenosine stimulation. The existence of a postsynaptic D-2/A-2 interaction is suggested, the stimulation of A-2 receptors causing an inhibition of responses elicited by postsynaptic D-2 stimulation.

Adenosine↗