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M Herrera-Marschitz

Publications and source records attributed to M Herrera-Marschitz.

At least 109 records · Page 6Linked to original sources
PubMed1990

Regulation of neuropeptide Y gene expression in rat brain.

NPY mRNA expression was studied in rat brain using in situ hybridization and RNA blot analysis. Transsynaptic regulation of NPY gene expression was specifically studied in caudate-putamen and frontoparietal (somatosensory) cortex of rats with unilateral lesion of midbrain dopamine neurons and in sham-injected animals. NPY mRNA expression in these two brain regions and the regulation of midbrain dopamine neurons were compared with that of SOM, PPT, CCK and GAD mRNA expression. Neurons expressing NPY and SOM mRNA showed a similar distribution and the expression of both NPY and SOM appears to be regulated by dopamine in a similar fashion. Following a unilateral dopamine deafferentation, the numerical density of both NPY and SOM mRNA expressing neurons almost doubled in the lesioned rat caudate-putamen with no change in the average grain density over positive neurons. Hence, in the intact caudate-putamen dopamine appears to normally suppress expression of these two neuropeptide genes. An activation of both NPY and SOM mRNA expression in many non- or low-expressing neurons is seen when the level of dopamine is decreased. In the frontoparietal cortex, on the other hand, dopamine appears to stimulate NPY and SOM gene expression. RNA blot analysis shows clear-cut changes of NPY mRNA levels in both caudate-putamen and frontoparietal cortex consistent with the changes observed using in situ hybridization. No evidence was found for a change in CCK mRNA expression by the dopamine deafferentation, while PPT mRNA expression decreased in the deafferented caudate-putamen. Consequently, dopamine exerts dissimilar effects on the expression of different neuropeptide genes, that in turn do not respond in the same way in different brain regions. Indirect evidence is also presented indicating that dopamine regulates NPY mRNA expression in a subpopulation of neurons that possibly also express GAD mRNA, both in caudate-putamen and in frontoparietal cortex.

Animals↗
PubMed1989

Mesencephalic dopamine innervation of the frontoparietal (sensorimotor) cortex of the rat: a microdialysis study.

Results obtained in a study using an in vivo microdialysis technique show that dopamine is detected in perfusates collected from the frontoparietal (sensorimotor) cortex of control rats (dopamine = 0.7 +/- 0.2 nM, n = 10) or of rats with cortical lesions produced by the neurotoxin kainic acid (0.9 +/- 0.2 nM, n = 4). However, cortical dopamine levels were strongly reduced (0.07 +/- 0.06 nM, n = 4) following deafferentation induced by mesencephalic 6-hydroxydopamine injection. Dopamine levels, but not its metabolites could be increased by local KCl application, supporting the idea that extracellular dopamine collected by microdialysis reflects a pool of releasable neurotransmitter.

Animals↗
PubMed1989

Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain.

In situ hybridization histochemistry and RNA blots were used to study the expression of glutamic acid decarboxylase (GAD) mRNA in rats with or without a unilateral lesion of midbrain dopamine neurons. Two populations of GAD mRNA positive neurons were found in the intact caudate-putamen, substantia nigra and fronto-parietal cortex. In caudate-putamen, only one out of ten of the GAD mRNA positive neurons expressed high levels, while in substantia nigra every second of the positive neurons expressed high levels of GAD mRNA. Relatively few, but intensively labelled neurons were found in the intact fronto-parietal cerebral cortex. In addition, one out of six of the GAD mRNA positive neurons in the fronto-parietal cortex showed a low labeling. On the ipsilateral side, the forebrain dopamine deafferentation induced an increase in the number of neurons expressing high levels of GAD mRNA in caudate-putamen, and a decrease in fronto-parietal cortex. A smaller decrease was also seen in substantia nigra. However, the total number of GAD mRNA positive neurons were not significantly changed in any of these brain regions. The changes in the levels of GAD mRNA after the dopamine lesion were confirmed by RNA blot analysis. Hence, midbrain dopamine neurons appear to control neuronal expression of GAD mRNA by a tonic down-regulation in a fraction of GAD mRNA positive neurons in caudate-putamen, and a tonic up-regulation in a fraction of GAD mRNA positive neurons in fronto-parietal cortex and substantia nigra.

Animals↗
PubMed1989

Rotational behaviour produced by intranigral injections of bovine and human beta-casomorphins in rats.

The biological activity of beta-casein derived beta-casomorphin peptides was evaluated by injecting bovine beta-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), the homologous sequence in human beta-casein (Tyr-Pro-Phe-Val-Glu) and the corresponding N-terminal tetrapeptides into the left substantia nigra of rats. Their ability to produce rotational behaviour was compared to that produced by three reference compounds, morphine, D-ala2D-leu5 enkephalin and U50,488H, ligands for mu, delta and kappa types of opioid receptors, respectively. The relative potencies of beta-casomorphins and morphine were compared to those tested in two in vitro assays for opioid activity: (1) inhibition of the electrically induced contraction of the isolated myenteric plexus-longitudinal muscle of the guinea-pig ileum and (2) displacement of 3H-dihydromorphine binding to brain membranes. The same ranking order of potency was found in all three assays, the peptides from human beta-casein being about 10-fold less potent than those from bovine beta-casein. The effects of both morphine and bovine beta-casomorphin-5 in producing rotational behaviour were antagonized by naloxone; however, approximately 10-fold more naloxone was required to antagonize the beta-casomorphin-5 effect than that of morphine. The present data are discussed in the light of the recent observation that high concentrations of beta-casomorphin-like peptides are found in the cerebrospinal fluid and plasma of women with postpartum psychosis.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Striatal and cortical acetylcholine release in vivo in rats with unilateral decortication: effects of treatment with monosialoganglioside GM1.

Striatal and cortical extracellular acetylcholine (ACh) and choline (Ch) levels were determined in samples collected under in vivo conditions using microdialysis in normal (naive) and decorticated rats treated with saline or the monoganglioside GM1. ACh and Ch were assayed using a sensitive high performance liquid chromatography technique coupled to a postcolumn reactor with immobilized enzymes. Picomole amounts of ACh could be measured in the presence of an acetylcholinesterase inhibitor (neostigmine) in the microdialysis perfusion medium (striatal ACh = 0.2-0.4 microM; cortical ACh = 0.03-0.04 microM). Ch was detected both in the presence and in the absence of neostigmine (striatal Ch = 0.5-0.6 microM; cortical Ch = 0.6-2 microM). ACh, but not Ch, was strongly stimulated by 100 mM of KCl included in the perfusion medium. Decortication produced by devascularization did not significantly modify the cortical or striatal basal levels of ACh. However, in the cortex, KCl produced a higher ACh stimulation in the GM1-treated than in the saline-treated decorticated or naive rats. The present results indicate that GM1-treatment increases the ability of cortical cholinergic terminals to release ACh and support the idea that trophic factors such as monoganglioside GM1 can promote recovery following injuries of the central nervous system.

Acetylcholine↗
PubMed1988

Differential modulation of striatal dopamine release by intranigral injection of gamma-aminobutyric acid (GABA), dynorphin A and substance P.

The effects of intranigral injection of gamma-aminobutyric acid (GABA) (dose range: 10.0-300.0 nmol), dynorphin A (0.005-0.5 nmol) and substance P (0.00007-7.0 nmol) on striatal dopamine (DA) release, and dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) formation were studied by microdialysis. It was found that both GABA and dynorphin A produced a dose-dependent decrease in the release of striatal DA following injection into the ipsilateral substantia nigra, the pars reticulata. In contrast, intranigral injection of substance P produced an increase in DA release. However, the dose-response curve for the substance P effect had a biphasic shape. The maximum effect was produced by 0.007 nmol, whereas higher doses (0.07-0.7 nmol) produced less pronounced effects. At the highest dose (7.0 nmol), substance P produced a strong decrease of DA release. Striatal levels of DOPAC and HVA were enhanced by GABA, dynorphin A and substance P. The present results support the concept that substance P, directly or indirectly, provides a positive feed-back regulation for the release of striatal DA, whereas GABA and dynorphin exert a negative feed-back regulation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Caffeine produces contralateral rotation in rats with unilateral dopamine denervation: comparisons with apomorphine-induced responses.

Like the dopamine agonist apomorphine, the methylxanthines caffeine, theophylline and theobromine produced dose-dependent contralateral rotation in rats with unilateral 6-hydroxydopamine denervation, a response considered to be dependent upon dopamine receptors rendered supersensitive. This response was also observed after the injection of the substances into the denervated striatum. Indeed, intrastriatal administration of caffeine into the dopamine denervated striatum produced, dose-dependently (1.0-50.0 micrograms/ul), contralateral rotation. However, while apomorphine produced ipsilateral rotation in rats with unilateral striatal kainic acid lesions, a response considered to be dependent upon normosensitive dopamine receptors, neither caffeine nor theophylline produced rotational responses. As for apomorphine, the rotational behaviour elicited by caffeine (15.0 mg/kg SC) and theophylline (25.0 mg/kg SC) was inhibited by the dopamine antagonists cis-(Z)flupentixol, haloperidol and sulpiride. Nevertheless, despite the fact that cis-(Z)flupentixol was the most potent inhibitor of the caffeine response, no more than 50% inhibition was produced with doses as high as 1.0-10.0 mg/kg SC of cis-(Z)flupentixol. Pretreatment with alpha methyl-p-tyrosine inhibited the rotational response produced by caffeine in 6-OHDA-lesioned animals, but did not significantly modify the apomorphine response. Furthermore, the benzodiazepine diazepam produced a dose-dependent inhibition of the caffeine rotation, but again, the apomorphine response, although qualitatively modified, was not significantly inhibited.

Animals↗
PubMed1987

Striatal adenosine levels measured 'in vivo' by microdialysis in rats with unilateral dopamine denervation.

Adenosine, inosine, hypoxanthine and guanosine were measured in perfusates collected from the right and left striatum of halothane-anaesthetized naive and 6-hydroxydopamine-denervated rats by using microdialysis. Samples were taken under basal and KCl-stimulated conditions. Dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were simultaneously measured. Purines and monoamines were assayed by HPLC-UV and HPLC-EC respectively. In naive rats, basal adenosine (1 microM), inosine (2 microM), hypoxanthine (4 microM), guanosine (0.5 microM) and dopamine (DA, 0.02 microM) levels (corrected by using the in vitro % recovery of each probe) were increased by the inclusion of 100 mM of KCl into the perfusion medium (2.5-, 3-, 3.5-, 1.5- and 30-fold, respectively, while DOPAC (6 microM), HVA (5 microM) and 5-HIAA (3 microM) levels were (72%, 68% and 45% respectively). DA was strongly diminished in the denervated striatum, but when detectable, could be increased (1- to 12-fold) by KCl stimulation. Adenosine, inosine, hypoxanthine and guanosine were, however, largely unaffected by the DA denervation and could be enhanced by KCl stimulation (2-, 3-, 4- and 1.5-fold respectively). The present results indicate that: (1) as in the case for DA, there is a pool of striatal adenosine which is releasable by high concentrations of extracellular K+; however, (2) this pool of adenosine seems not to be significantly modified by mesencephalic dopamine deafferentation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

The dopamine-gamma aminobutyric acid interaction in the striatum of the rat is differently regulated by dopamine D-1 and D-2 types of receptor: evidence obtained with rotational behavioural experiments.

The effects of GABA antagonists on apomorphine- and pergolide-induced rotational behaviour were studied with models combining intracerebral and systemic pharmacological treatments. Whether given systemically or intrastriatally to 6-hydroxydopamine-lesioned rats, the GABA antagonist picrotoxin inhibited the rotational responses produced by s.c. administration of the dopamine (DA) D-1/D-2 agonist apomorphine while it enhanced the rotational behaviour produced by the DA D-2 agonist pergolide. Following unilateral injection of picrotoxin or bicuculline into the striatum of naive rats, apomorphine produced ispsilateral rotation, while pergolide produced contralateral rotation. These contrasting effects are compared to the behavioural responses produced by intracerebral administration of GABAergic drugs alone. Intrapallidal injection of picrotoxin produced contralateral rotational behaviour which was independent of pallido-nigral pathways. Contralateral rotation was also produced by GABA agonists, but only following intranigral injections. The results are discussed in terms of differences in the localization of DA D-1 and DA D-2 receptors on striatal GABAergic neurons. The DA D-2 receptor agonist pergolide may induce inhibition of striato-pallidal GABAergic neurons, as well as of a local GABAergic circuit exerting inhibition on a striato--pallidal enkephalinergic pathway. However, the DA D-1/D-2 receptor agonist apomorphine may inhibit striatal interneurons exerting inhibition on a striato-nigral GABAergic projection. Such a neuronal arrangement may explain that striatal DA stimulation increases GABA release from the striato-nigral terminals.

Animals↗
PubMed1986

gamma-Aminobutyric acid release in the globus pallidus in vivo after a 6-hydroxydopamine lesion in the substantia nigra of the rat.

This experiment was designed to determine whether the release of gamma-aminobutyric acid (GABA) in the globus pallidus (GP) is affected by a lesion of the nigrostriatal pathway. Rats were lesioned with 6-hydroxydopamine 4 weeks prior to study of the in vivo release of GABA. A microdialysis probe was stereotaxically implanted in halothane-anesthetized animals in a vertical position on both GPs. The perfusates were analyzed for their GABA content with a high performance liquid chromatography technique. Compared to unlesioned controls, a marked decrease in the overflow of GABA was observed in the GP contralateral to the lesion, whereas the ipsilateral GP showed a slight increase. The differences between the sides were exaggerated after KCl (100 mmol) administration. The results are discussed in terms of a possible bilateral influence of dopamine terminals in the striatum on GABA transmission.

Animals↗
PubMed1986

Simultaneous measurement of dopamine release and rotational behaviour in 6-hydroxydopamine denervated rats using intracerebral dialysis.

Amphetamine- and L-DOPA-induced changes in extracellular levels of striatal dopamine (DA) were monitored during rotational behaviour in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal DA pathway. In vivo DA release measurements were obtained using intracerebral dialysis combined with high-performance liquid chromatography with electrochemical detection (HPLC-ED). In unilaterally denervated rats no DA was detected in dialysates collected from the striatum ipsilateral to the lesion while the contralateral side showed a compensatory increase in basal DA levels when compared to non-lesioned controls. Amphetamine (0.5-5.0 mg/kg s.c.) caused a dose-dependent release of DA in the striatum of normal rats and in the intact striatum of DA denervated rats but did not significantly release DA in the lesioned striatum. In response to amphetamine (0.5-5.0 mg/kg s.c.) lesioned animals showed dose-related ipsilateral rotational behaviour which in general correlated well with the time-course change in, and the total amount of, DA release in striatum contralateral to the lesion. In contrast to amphetamine, in lesioned rats, the DA precursor L-DOPA (20 mg/kg s.c.) induced readily detectable amounts of DA in dialysates collected from the DA denervated striatum. The L-DOPA-induced appearance of DA, which approached basal DA levels seen on the intact side, was concomitant with contralateral rotational behaviour. However, the time-course change in DA levels did not closely correlate with the apparently two-peak pattern of contralateral rotation induced by L-DOPA.

Amphetamine↗
PubMed1986

Striato-nigral dynorphin and substance P pathways in the rat. I. Biochemical and immunohistochemical studies.

The effect of striatal ibotenic acid lesions on dynorphin-, substance P- and enkephalin-like immunoreactivities in the substantia nigra has been studied with immunohistochemistry as well as biochemistry. A comparison was made with the effects produced by intranigral ibotenic acid lesion and by 6-hydroxy-dopamine injection into the medial forebrain bundle. In addition, the effect of the striatal lesions on nigral glutamic acid decarboxylase (GAD)-positive structures was analysed with immunohistochemistry. The effect of the lesions was analysed functionally in the Ungerstedt rotational model, in order to obtain a preliminary evaluation of the extent of the lesions. The striatal lesions produced a parallel depletion of dynorphin and substance P levels in the substantia nigra, pars reticulata, ipsilateral to the treated side, which was dependent upon the extent and location of the lesion. Ibotenic acid lesions into the tail and the corpus of the striatum produced stronger nigral-peptide depletion than lesions in the head and the corpus of the striatum. Comparison of placement of lesions and localization of depleted area in the substantia nigra revealed a topographical relationship. Furthermore, the nigral depletion patterns of dynorphin and substance P were similar. The immunohistochemical analysis revealed that also GAD-positive fibers in the pars reticulata to a large extent disappeared after striatal lesions, in parallel to the dynorphin- and substance P-positive fibers. However, the depletion was less pronounced for GAD than for the peptides, probably related to presence of local GABA neurons in the zona reticulata of the substantia nigra. These results indicate that with the types of lesion used in this study it is not possible to provide evidence for a differential localization within the striatum of dynorphin-, substance P- and GABA-positive cell bodies projecting to the substantia nigra. The radioimmunoassay showed that (Leu)- but not (Met)-enkephalin was affected to the same extent as the dynorphin peptides, supporting the view that (Leu)-enkephalin in the pars reticulata of the substantia nigra is derived from proenkephalin B and not from proenkephalin A. In the immunohistochemical analysis (Met)-enkephalin-like immunoreactivity could only be detected in the pars compacta of the substantia nigra and did not seem to be affected by any of the lesions. The striatal lesions produced a behavioural asymmetry, which could be disclosed by stimulating the rats with apomorphine, which produced ipsilateral rotation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Striato-nigral dynorphin and substance P pathways in the rat. II. Functional analysis.

In the present study the functional role of the striato-nigral dynorphin and substance P pathways in rat brain has been studied using the rotational behavioural model and an intracerebral dialysis technique complemented with brain lesions and immunohistochemical analysis. Attempts were made to evaluate whether these striato-nigral neurons have a feed-back modulatory action on the dopaminergic nigro-striatal system, or whether they represent an outflow pathway conveying motor information from the striatum. Unilateral injection of dynorphin A into the substantia nigra reticulata of naive rats induced contralateral rotational behaviour. This effect was dose-dependent and mimicked by the kappa-opioid receptor agonist, U50,488H. Intranigral injection of substance P, as well as substance K, also produced dose-dependent contralateral rotational behaviour. Unilateral injections of ibotenic acid into various sites of the striatum were used to destroy the striato-nigral pathways. The lesions produced a depletion of dynorphin- and substance P-like immunoreactivity in the pars reticulata of the substantia nigra ipsilateral to the lesion and markedly affected the behavioural responses to intranigral peptide injections. Dynorphin A more potently induced contralateral rotation in the lesioned compared to naive non-lesioned rats, suggesting development of supersensitivity for this peptide. Substance P on the other hand, was markedly less potent in inducing rotation in lesioned animals. The rotational responses to both dynorphin A and substance P were potentiated by injection of amphetamine 1 h later, suggesting that both peptides act via nigro-striatal dopamine neurons. However, in rats with unilateral nigro-striatal dopamine denervation, produced with 6-hydroxy-dopamine, dynorphin A retained its potency to induce rotational behaviour; substance P was again much less potent. Thus, both the ibotenic acid and 6-hydroxy-dopamine lesions differently affect the action of dynorphin A and substance P in the zona reticulata of the substantia nigra. The data suggests that substance P requires an intact dopamine pathway to produce the rotational response, while dynorphin A does not. Direct evidence that behavioural activation produced by dynorphin A is not dependent upon dopamine stimulation was obtained by intrastriatal dialysis experiments in which changes in striatal dopamine release were measured following intranigral injection of dynorphin A or substance P. Intranigral dynorphin A in fact reduced, while substance P increased the release of dopamine.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

The benzazepine SCH 23390 increases plasma levels of cortisol in the conscious dog.

The effect of neuroleptics on the hypothalamopituitary-adrenal system has been early recognized, but never adequately related to antipsychotic or side effects produced by dopamine antagonists. We are now presenting results showing that the newly characterized dopamine D-1 receptor antagonist, SCH 23390 (0.1 mg/kg i.v.) as well as the mainly dopamine D-2 receptor antagonists, haloperidol (0.1 mg/kg i.v.) and chlorpromazine (1 mg/kg i.v.), produced an increase of cortisol levels (108, 144 and 226% respectively, 20 min after the injection) determined by radioimmunoassay in blood samples collected from superficial veins of the legs of conscious dogs. The 5-HT2 receptor antagonist, cyproheptadine (0.2 mg/kg i.v.), did not modify the cortisol levels. These results suggest that cortisol increase is an effect common to neuroleptic compounds, independently of their relative antagonistic action at dopamine D-1 or D-2 receptors.

Animals↗
PubMed1985

Effect of the dopamine D-1 antagonist SCH 23390 on rotational behaviour induced by apomorphine and pergolide in 6-hydroxy-dopamine denervated rats.

The experiments concerned the effects of the D-1 dopamine antagonist SCH 23390 on the rotational behaviour induced by apomorphine and pergolide in 6-hydroxy-dopamine denervated rats. SCH 23390 dose dependently inhibited the rotational behaviour induced by apomorphine. A significant inhibitory effect was obtained after 0.05 mg/kg s.c. of SCH 23390, which involved a change of the typical two-peak pattern of rotation induced by apomorphine. While the first peak of rotation was not significantly modified, the last peak of rotation induced by apomorphine was inhibited in a dose-dependent manner. No significant inhibition of the total rotation induced by pergolide was observed after SCH 23390 pretreatment. SCH 23390 seemed to enhance the duration of the rotation induced by pergolide, resulting in an increase in the total number of turns. However, the intensity of the maximal peak of rotation induced by pergolide was significantly inhibited after 5.0 mg/kg s.c. of SCH 23390. Comparison of the potency with which SCH 23390 inhibited the apomorphine- and pergolide-induced maximal peaks of rotation reveals that SCH 23390 was approximately 100 times more potent in inhibiting the apomorphine than the pergolide response. The results, compared with those in our previous report, show that the D-2 dopamine antagonist sulpiride was 1000 times more potent in inhibiting the pergolide than the apomorphine rotation. The present results support the hypothesis that apomorphine and pergolide induce rotation in 6-hydroxy-dopamine denervated rats by differential actions on D-1 and D-2 receptor sites.

Animals↗