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Biomedical subjects

G Pepeu

Publications and source records attributed to G Pepeu.

At least 163 records · Page 9Linked to original sources
PubMed1982

In vitro changes in gamma-aminobutyric acid output from the cerebral cortex induced by inhibitors of gamma-aminobutyric acid uptake and metabolism.

The effects of inhibitors of gamma-aminobutyric acid (GABA) metabolism or uptake on GABA output from the cerebral cortex was studied by means of a collecting cup placed on the exposed cortex of rats anaesthetized with urethane. GABA was identified and quantified by a mass-fragmentographic method. Ethanolamine-O-sulphate (10(-2) M) applied directly on the cerebral cortex caused a long-lasting twofold increase in GABA output, whereas DL-2,4-diaminobutyric acid (5 X 10(-3) M) caused a sevenfold increase and beta-alanine was active. The results indicate that glial uptake has little effect on GABA inactivation in the cerebral cortex. The inhibition of neuronal uptake seems a more effective tool to increase GABA concentration in the synaptic cleft, and consequently also in GABA output, than the inhibition of GABA metabolism.

Aminobutyrates↗
PubMed1982

Effects of 4-aminopyridine on acetylcholine output from the cerebral cortex of the rat in vivo.

1 The effects of 4-aminopyridine (4AP) on the output of acetylcholine (ACh) from the cerebral cortex were investigated in unanaesthetized freely moving rats and in anaesthetized rats by means of the ;cup technique'. ACh was determined by bioassay on the dorsal muscle of the leech.2 In unanaesthetized rats intraperitoneal injection of 4AP (3 mg/kg) had no effect on the cortical output of ACh.3 After injection of morphine (10 mg/kg s.c.), which depressed the spontaneous output of ACh, 4AP increased the cortical output to a level significantly higher than that determined before morphine injection.4 In rats anaesthetized with either urethane or pentobarbitone, drugs known to decrease cortical output of ACh, 4AP (i.v. or i.p.) elicited a significant increase in the output of ACh. The time-courses of the 4AP-induced effects were different depending on the anaesthetic drug used: an immediate increase slowly fading in urethane anaesthesia and a gradual increase after delayed onset in pentobarbitone-anaesthetized rats.5 In some urethane-anaesthetized rats, respiratory frequency was kept constant (tracheotomy, connection to respirator, bilateral vagotomy) and prazosin (1 mg/kg i.v.) was administered to reduce the 4AP-induced increase of blood pressure. Cortical output of ACh was not related to changes in blood pressure. Moreover, the 4AP-induced increase in cortical ACh output was not related to changes in respiratory frequency.6 In summary systemic administration of 4AP in subconvulsive doses (1 and 3 mg/kg) increased cortical output of ACh in rats anaesthetized with urethane or pentobarbitone or after injection of morphine, but not in untreated freely moving rats. It is suggested that the anaesthetic agents and morphine may cause an imbalance between excitatory and inhibitory central pathways, and that this imbalance may play a role in their depressant effect on cortical output of ACh and/or in the 4AP-induced facilitation described in this paper.

4-Aminopyridine↗
PubMed1982

Effect of magnocellular forebrain nuclei lesions on acetylcholine output from the cerebral cortex, electrocorticogram and behaviour.

ACh output from the cerebral cortex, electrocortical activity, spontaneous alternation and the acquisition of a conditioned avoidance response have been investigated in rats 20 days after the placement of a unilateral lesion of the magnocellular forebrain nuclei (MFN). ACh output from the hemisphere ipsilateral to the lesion was 40% lower than in sham operated rats. Electrocortical activity quantified with a frequency analyzer supplemented by a period and power spectrum analysis showed a marked asymmetry between the two hemispheres of the lesioned rats. The total electrical activity was strongly reduced over the lesioned hemisphere. The reduction involved all frequencies but was more evident in the high frequencies. In the lesioned rats spontaneous alternation was not impaired and spontaneous motility was enhanced while the acquisition of a conditioned active avoidance in a two-way shuttle box was significantly hampered. The possibility is envisaged that the destruction of cholinergic fibres impinging upon the cerebral cortex may decrease cortical activation and impair the selective awareness necessary for information acquisition and exclusion of irrelevant output.

Acetylcholine↗
PubMed1981

The release of endogenous GABA and glutamate from the cerebral cortex in the rat.

1. The release of endogenous GABA and glutamate from the cerebral cortex was measured using a cortical cup technique in unanaesthetized freely moving rats and anaesthetized rats by means of a sensitive and specific mass-spectrometric procedure. 2. GABA release was not affected by the presence of the dura mater or by anaesthesia. Glutamate output was reduced by urethane but not by pentobarbital anaesthesia and by the presence of the dura. 3. An isotonic solution containing 50 mM KCl placed epidurally within the cup elicited a significant short-lasting increase in glutamate output, a decrease in GABA output and a short-lasting electrocorticogram (ECoG) activation. 4. When the dura was removed, a high K+ solution placed on the exposed cerebral cortex elicited a 7--8 fold increase in GABA output accompanied by a marked decrease in glutamate output and by ECoG synchronization. The changes in GABA and glutamate output had parallel time-course and were prevented by the application within the cup of tetrodotoxin (3 X 10(-5) M). 5. Amphetamine at the doses of 3.7 and 7.4 mumol . kg-1 i.v. increased glutamate output and at the dose of 37 mumol . kg-1 i.v. increased GABA output. Both effects were prevented or reduced by haloperidol pretreatment (0.65 mumol . kg-1 i.v.). 6. It is concluded that GABA and glutamate released from the cerebral cortex and diffused into an epidural or cortical cup originate at least in part from the brain. The rate of their release is influenced by changes in neuronal activity. The measurement of their rate of release offers a useful tool for the study of the functional role of cortical GABA and glutamate-releasing neurons.

Amino Acids↗
PubMed1981

Changes in synaptosomal high affinity choline uptake following electrical stimulation of guinea-pig cortical slices: effect of atropine and physostigmine.

1 Superfused guinea-pig cortical slices were electrically stimulated at different frequencies and the changes in acetylcholine (ACh) content measured. Synaptosomes were prepared at the end of the stimulation period and high affinity choline uptake (HACU) rate was measured. 2 The effect of increasing KC1 concentrations was compared on ACh content of the slices and on synaptosomal HACU. 3 Electrical stimulation (2, 5, 10, 20 Hz) elicited a frequency-dependent linear increase in synaptosomal HACU rate and a decrease in ACh content of the slices. 4 The addition of atropine (1.5 x 10(-8) M) to the slices enhanced and that of physostigmine (3 x 10(-5) M) reduced the frequency-dependent increase in HACU rate. Atropine (1.5 x 10(-6) M) not only antagonized the effect of physostigmine, but the HACU rate measured after treatment with both drugs was larger than that found after atropine alone. 5 These results indicate that in the cortical cholinergic nerve endings, depolarization caused by electrical stimulation is coupled with an increase in choline transport which can be modulated by the addition of atropine or physostigmine. Furthermore, within given experimental conditions a linear relationship exists between the reciprocal of ACh content in the slices and synaptosomal HACU.

Acetylcholine↗
PubMed1980

Effect of haloperidol and pimozide on acetylcholine output from the cerebral cortex in rats and guinea pigs.

The effect of haloperidol, pimozide and amphetamine on acetylcholine (ACh) output from the cerebral cortex was investigated in unanaesthetized, freely moving and urethane-anaesthetized rats and guinea pigs. Haloperidol (1 mg/kg i.p.) decreased ACh output only in the anaesthetized rats and increased it only in unanaesthetized guinea pigs. Pimozide (1 mg/kg i.p.) stimulated ACh output in unanaesthetized rats and guinea pigs and anaesthetized guinea pigs, but not in anaesthetized rats. Amphetamine (1 mg/kg i.p.) in all cases, stimulated ACh output. In rats with a septal lesion, the effect of amphetamine on ACh output was suppressed but that of pimozide was still present.

Acetylcholine↗
PubMed1980

Choline high-affinity uptake and metabolism and choline acetyltransferase activity in the striatum of rats chronically treated with neuroleptics.

High-affinity uptake of choline and choline acetyltransferase activity (ChAT) were measured in the striatum of rats treated for 45-60 days with haloperidol (1 mg/kg per os) and pimozide (1 mg/kg per os) daily and with fluspirilene (1 mg/kg i.m.) twice a week. Haloperidol and fluspirilene caused a 20%, and pimozide a 38%, increase in high-affinity uptake of choline. They also caused a significant decrease in ChAT activity: haloperidol, 20%; pimozide, 27%; and fluspirilene, 42%. In rats treated with fluspirilene for 65-80 days the metabolism of [3H] choline taken up by striatal synaptosomes was investigated. A 33% increase in total radioactivity, a significant increase in labelled acetylcholine (ACh), a relative decrease in labelled choline, and no change in labelled phosphorylcholine and betaine were found. It is concluded that the increase in high-affinity choline uptake caused by chronic administration of neuroleptic drugs is associated with a parallel increase in choline utilization for ACh formation. On the other hand, the decrease in ChAT activity does not appear to influence ACh formation.

Animals↗
PubMed1979

Psychopharmacological prospectives in the treatment of dementia.

1. Dementias have a complex etiology and pathogenesis which should be carefully evaluated in order to attempt a medical treatment. 2. Drugs are among the most frequent causes of dementias, particularly drugs with anticholinergic properties. 3. A similarity between the mental symptoms of anticholinergic poisoning and senile dementia has been observed. 4. Recent investigations have also presented a decrease of cholinergic activity in postmortem material of subjects with Alzheimer's disease. Also a number of data suggest that recent memory would be related to changes in the metabolism of brain acetylcholine (Ach). 5. The possibility that drugs stimulating brain cholinergic mechanisms might be used in the treatment of dementias is envisaged.

Central Nervous System↗
PubMed1978

Stimulation of acetylcholine output from brain slices caused by the ionophores BrX-537A and A23187.

1 The effect of two ionophores, BrX-537A (Bromolasolacid) and A 23187, on acetylcholine (ACh) output from brain slices was studied. 2 The slices were prepared from rat cerebral cortex, incubated in Krebs solution containing physostigmine and ACh output determined by bioassay. 3 Both ionophores enhanced ACh output. BrX-537A exerted its maximal effect, a six fold increase, at a concentration of 1.8 micron, while A 23187 caused a three fold increase at a concentration of 58 micron. 4 When the slices were incubated in a Ca-free medium, the effect of A 23187 on ACh output was only reduced, BrX-537A was abolished while that of BrX-537A was also active when disodium edetate (EDTA) was added to the the Ca-free medium. 5 The activity of BrX-537A was not affected by the presence of tetrodotoxin in the incubation medium. 6 The stimulation of ACh output elicited by KCl (25 mM) was increased further by hyoscine, but not by BrX-537A. Hyoscine however had no effect when ACh output was stimulated by BrX-537A. 7 The effect of BrX-537A on ACh output was potentiated by the addition of Mg2+ (9.3 mM) to the incubation medium and was reduced in a Mg-free medium. 8 It is concluded that A 23187 stimulates ACh output by transporting extracellular Ca2+ into cholinergic nerve endings. The effect of BrX-537A does not depend only on Ca2+ but also on other mechanisms.

Acetylcholine↗