Biomedical subjects

M Goiny

Publications and source records attributed to M Goiny.

At least 19 recordsLinked to original sources

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

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

Grafting of genetically modified cells: effects of acetylcholine release in vivo.

In this study, microdialysis was used to investigate functional recovery of central cholinergic neurons in the forebrain of rats with cortical devascularizing lesions. Mature male rats were unilaterally lesioned by disruption of the pia arachnoid vessels and genetically modified fibroblasts secreting nerve growth factor (NGF) were placed at the site of the lesion. One month following surgery, microdialysis probes were installed in the remaining cortex and were perfused with artificial cerebrospinal fluid (csf) containing neostigmine (5 nM) and/or KCl (100 mM). The basal (non-stimulated) release of acetylcholine (ACh) in the cortex was similar in all experimental groups, whereas KCl stimulated release of ACh was significantly augmented (P < 0.05) in the ipsilateral remaining cortex in lesioned animals that have been implanted with fibroblasts secreting NGF. These results suggest that NGF secreted by genetically engineered fibroblasts modulates neuroplasticity in the adult mammalian CNS and may favour recovery of cortical function following injury.

Acetylcholine↗

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

Enhanced in vivo release of substance P in the nucleus tractus solitarii during hypoxia in the rabbit: role of peripheral input.

In the adult, pentobarbitone-anaesthetized rabbit, the in vivo release of substance P-like immunoreactivity was measured in the nucleus tractus solitarii using microdialysis and radioimmunoassay. Increased 160 +/- 16%) extracellular concentrations of substance P-like immunoreactivity were observed during hypoxic provocations of 9% O2 in N2 which also resulted in an increase in phrenic nerve activity. In bilateral carotid sinus nerve-denervated animals no enhanced release of substance P was seen in response to hypoxic challenges (105 +/- 6%) and the phrenic nerve activity was not significantly affected. Perfusion of the nucleus tractus solitarii region with the dopamine agonist, apomorphine (10(-5) M) resulted in a significant decrease in the extracellular level of substance P. These results provide further evidence that substance P is involved in the mediation of the hypoxic drive inputs from the peripheral chemoreceptors. The interactions of apomorphine with substance P release might also suggest a presynaptic modulation of substance Pergic neurons by dopamine in the nucleus tractus solitarii.

Animals↗

PubMed1991

Responses of blood flow, extracellular lactate, and dopamine in the striatum to intrastriatal injection of endothelin-1 in anesthetized rats.

Recently a histological study has demonstrated that intrastriatally injected endothelin-1 (ET-1) produced ischemia-like lesions in the neostriatum. The present study was undertaken to investigate whether intrastriatally injected ET-1 produces ischemic responses such as a decrease in the striatal blood flow and increases in extracellular lactate and dopamine levels in the neostriatum as seen in other models of ischemia. A small needle (for injection of ET-1), a microdialysis probe (for collecting extracellular substances), and a probe of a laser Doppler flowmeter (for measuring local cerebral blood flow) were implanted with their tips close to each other in the neostriatum of halothane-anesthetized rats. Focal administration of ET-1 (430 pmol) into the neostriatum resulted in a marked decrease in striatal blood flow without any change in systemic blood pressure. It also markedly increased extracellular lactate and dopamine levels, whereas it decreased pyruvate and dopamine metabolite levels. These changes agreed well with those known to be produced by ischemia. Intracerebral injection of ET-1 will therefore provide a new model for production of local ischemia in experimental animals.

Anesthesia↗

PubMed1991

Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits.

A wide variety of neuroactive substances have been suggested to be involved in the respiratory depression observed in response to severe hypoxia. By use of the technique of microdialysis, the release of dopamine (DA) was measured in the nucleus tractus solitarii during severe hypoxic provocations (6% O2 in N2) in the adult pentobarbital-anesthetized rabbit. DA release was analyzed by high-performance liquid chromatography with electrochemical detection. Such hypoxic provocations caused pronounced phase of depression in the phrenic nerve activity and enhanced release of DA. After bilateral carotid sinus nerve denervation, acute severe hypoxia did not give rise to enhanced release of DA or to phrenic nerve depression. Mild hypoxic (9% or 12% O2 in N2) or hypercapnic (6% CO2) stimuli resulted in an increased phrenic nerve activity without any concomitant changes in DA release. Decerebration at the midcollicular level in rabbits prevented an enhanced release of DA in the nucleus tractus solitarii during severe hypoxia. The results suggest that 1) DA is involved in the central ventilatory response to severe hypoxia, 2) not only the initial excitatory but also the second depressive phase in response to severe hypoxia is mediated partially by the peripheral chemoreceptors, and 3) the depressive phase is dependent on intact connections from suprapontine structures.

Animals↗

PubMed1990

In vivo release of serotonin in cat dorsal vagal complex and cervical ventral horn induced by electrical stimulation of the medullary raphe nuclei.

Extracellular levels of serotonin (5-hydroxytryptamine; 5-HT) were monitored by microdialysis in the dorsal vagal complex (DVC) and the ventral horn of the spinal cord at the level of the phrenic motor nucleus in decerebrated cats. A selective serotonin uptake inhibitor, alaproclate (10(-4) M) was included in the dialysis probe perfusion fluid to increase basal and stimulated levels of 5-HT. Electrical stimulation (30 Hz, 10 V, 0.5 ms) in the nucleus raphe obscurus, containing neurons projecting to the DVC and to the ventral horn, induced a 2-3-fold increase of the 5-HT release in both these regions. After termination of the stimulation, the release gradually decreased during the following 60 min. Substance P, which coexists with 5-HT in descending neurons, did not significantly affect the 5-HT release when it was added (100 microM) to the probe perfusion fluid. The present findings are in accordance with the hypothesis that prolonged release of 5-HT is responsible for the previously demonstrated long-lasting facilitation of phrenic activity following raphe obscurus stimulation.

Animals↗

PubMed1990

Effect of unilateral nucleus basalis lesion on cortical and striatal acetylcholine and dopamine release monitored in vivo with microdialysis.

Cortical and striatal extracellular acetylcholine (ACh), choline (Ch), dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels were estimated in samples collected with microdialysis in halothane-anaesthetized rats which had received 0.6 microliter of ibotenic acid (5 micrograms/microliters) into the left nucleus basalis magnocellularis (microdialysis experiments were performed 3-4 weeks after the lesion). Samples were collected under basal (Ringer or Ringer including 10 microM neostigmine) and KCl (100 mM)-stimulated conditions. In the intact frontoparietal cortex and striatum, basal ACh (only detected under neostigmine perfusion) was in the 30 and 300 nM range, respectively. In the same conditions, Ch was in the 0.7 microM range in the cortex and in the 0.2 microM range in the striatum. The inclusion of KCl in the perfusion medium strongly enhanced cortical (greater than 7-fold) and striatal (greater than 10-fold) ACh. KCl only moderately increased striatal (65%) but not cortical Ch. In the lesion side, both basal and stimulated ACh were significantly reduced in the cortex (greater than 60%), but not in the striatum. Ch was not significantly changed in the cortex and striatum. The nucleus basalis lesion also produced a drop in extracellular levels of cortical and striatal DA (40% and 55%, respectively). Neither cortical nor striatal ACh levels were modified by a unilateral DA deafferentation (6-hydroxydopamine lesion into the medial forebrain bundle). However, the destruction of the intrinsic cortical ACh by injection of kainic acid into the frontoparietal cortex produced a 30% decrease in ACh.

3,4-Dihydroxyphenylacetic Acid↗

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↗

PubMed1987

Effects of dopamine receptor antagonists on gastrin and vomiting responses to apomorphine.

Apomorphine (0.05 mg/kg intravenously) was given to conscious dogs, and gastrin levels were measured in peripheral venous blood with a radioimmunoassay. Apomorphine induced an increase of gastrin levels which peaked at 5 min. The peripheral dopamine D-2/DA2 receptor antagonist domperidone (0.2 mg/kg), but not halopemide (0.1-1 mg/kg) nor the D-1/DA1 receptor antagonist SCH 23,390 (0.1 mg/kg), blocked the gastrin response to apomorphine. Both domperidone and halopemide, but not SCH 23,390, blocked the apomorphine-induced vomiting. These results suggest that apomorphine increases gastrin levels by an action at D-2/DA2 receptors, which are situated outside the blood brain barrier and differ from the receptor inducing the vomiting.

Animals↗

PubMed1987

A long lasting gastrin response to apomorphine revealed by inhibitors of gastric acid secretion.

Gastrin levels, in the peripheral venous blood of conscious dogs treated with apomorphine (0.05 mg/kg IV), were analysed with a radioimmunoassay. Pretreatment (30 min) with the gastric acid inhibitors cimetidine, ranitidine (H2 receptor antagonists, 4 mg/kg and 1 mg/kg respectively) or omeprazole (H+-K+ ATPase inhibitor, 1.6 mg/kg) prolonged the elevation of gastrin levels occurring in response to an administration of apomorphine. Haloperidol (0.1 mg/kg), but not the peripheral dopamine receptor antagonist domperidone (0.2 mg/kg), abolished the enhanced gastrin response to apomorphine occurring after pretreatment with cimetidine. Cimetidine did not increase the gastrin response to apomorphine in vagotomized dogs. The results are interpreted in terms of an additive gastrin response to apomorphine (different from the short lasting initial peak previously described) which is vagally mediated and inhibited by the gastric acid.

Animals↗

PubMed1986

Effects of dopaminergic drugs on plasma levels of steroid hormones in conscious dogs.

Progesterone, cortisol and testosterone levels were measured by radioimmunoassay in peripheral venous blood of conscious dogs. I.v. injections of the dopamine receptor agonists apomorphine (0.05 mg/kg) and bromocriptine (0.1 mg/kg) increased progesterone levels (and cortisol levels, as previously shown) in dogs of both sexes. The response to apomorphine was abolished by pretreatments with peripheral dopamine receptor antagonists (domperidone and halopemide). Progesterone and cortisol responses to the dopamine receptor agonists were parallel, but the ratio of concentration was 1/100. Testosterone levels were not modified. These results suggest that the dopamine receptor agonists stimulate progesterone release from the adrenal glands at a site functionally accessible to the peripheral dopamine receptor antagonists. In addition, the neuroleptic haloperidol (0.1 mg/kg) was shown to cause long lasting increases of progesterone levels.

Animals↗

PubMed1986

Bromocriptine and apomorphine stimulation of cortisol secretion in conscious dogs; evidence for a stimulatory site located outside the blood brain barrier.

IV injections of the dopamine receptor agonists bromocriptine (0.1 mg/kg) and apomorphine (0.05 mg/kg) induced rapid and long-lasting increases of cortisol levels as measured by RIA in peripheral venous plasma of conscious dogs. Pretreatment with dopamine receptor antagonists which do not readily penetrate the blood brain barrier (domperidone, halopemide, sulpiride) abolished the release responses induced by the dopamine agonists. These results suggest that the dopamine receptor agonists stimulate cortisol release at a site located outside the blood brain barrier. In addition, some dopamine receptor antagonists (haloperidol, chlorpromazine, milenperone) were shown to cause a rapid and long-lasting increase of cortisol levels.

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↗

PubMed1986

Effects of dopaminomimetics on the secretion of VIP-like immunoreactivity in conscious dogs.

The effects of some dopaminomimetics on VIP levels in peripheral venous blood of conscious dogs were analysed with a radioimmunoassay. The dopamine D2 agonist pergolide, like apomorphine and bromocriptine, increased VIP levels. The putative DA autoreceptor agonist 3PPP, as well as the D1 agonist SK&F 38393 were devoid of action. The D1 antagonist SCH 23390 did not abolish the effect of apomorphine. It is suggested that monitoring of VIP levels could be an interesting screening test for activity at D2 receptors. Amphetamine did not modify VIP levels suggesting that DA neurons are not involved in the mechanism leading to a release of VIP. The VIP response to apomorphine was not suppressed by an infusion of somatostatin. Decreasing blood pressure with nitroglycerin or with the adrenergic antagonist prazosin did not release VIP. The mechanism by which administration of dopaminomimetics lead to a release of VIP is further discussed.

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

PubMed1985

The kinetics of adrenal catecholamine secretion elicited by splanchnic nerve stimulation or by Ach is consistent with non-exocytotic, multivesicular release on cation exchange basis.

In eight anaesthetized cats, one dog and one pig the left adrenal was activated during a 5-15-min period by splanchnic nerve stimulation (10-30 V, 0.2-2 ms) at supramaximal frequencies (10-50 Hz) or by i.a. infusion of acetylcholine in high concentration (10(-4) M). The catecholamine (CA) release, as recorded in the adrenal venous outflow, was characterized by a very steep rise to a peak (within less than 10 s), followed by a rapid decline which after 5-10 min continued as a 'steady state' secretion, still above prestimulatory level. The initial release curve satisfied the straight line equation log B = K square root (sigma ml) + log Bmax, shown previously by us to be characteristic of the cation-induced amine release from amine-charged IRC 50 (a synthetic carboxyl cation exchanger resin) and from chromaffin granules in vitro which occurred on superfusion of these materials with isotonic NaCl solution (Uvnäs & Aborg 1984a). The initial CA-release, which depending on the intensity of the stimulus amounted to between 0.1 and approximately 5% of the adrenal CA content is suggested to reflect the rapid depletion of a CA pool for immediate release composed of granules 'lined up' for secretion adjacent to the plasma cell membrane. On depolarization of this membrane the granules are assumed to become attached to it and CA release to occur as a cation exchange, between CA+ in the granule matrix and Na+ in the plasma or possibly K+ in the cytoplasm. The transition from depletion to 'steady state' phase is assumed to reflect resynthesis or other compensatory refilling of the releasable depot evoked by its depletion. Cation exchange is suggested to be a general principle in the release of biogenic amines, including transmitter amines and other co-stored charged substances, e.g. polypeptides.

Acetylcholine↗