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Biomedical subjects

H Ladinsky

Publications and source records attributed to H Ladinsky.

At least 73 records · Page 4Linked to original sources
PubMed1983

Modifications in recognition sites for neurotransmitters in rat hippocampus by kainic acid lesion.

The specific binding of the tritiated radioligands of dexetimide, serotonin, clonidine, prazosin, WB-4101 and dihydroalprenolol to hippocampal membranes was determined two weeks after producing a virtual complete degeneration of perikarya by the local application of 0.5 micrograms of kainic acid in the dorsal and ventral parts of the hippocampus. Afferent terminals were unaffected by the neurotoxin since the contents of noradrenaline, serotonin and acetylcholine, as well as the activity of choline acetyltransferase, were not modified. Scatchard analysis revealed that the kainic acid lesion produced a 60% decrease in the density of both cholinergic muscarinic binding sites and serotonin binding sites. A significant portion of alpha 1- and alpha 2-adrenoceptor binding sites are also associated with intrinsic neurons of the hippocampus, as shown by the approximately 30% reduction in the densities of tritiated WB-4101, prazosin and clonidine produced by the action of kainic acid. By contrast, the affinity and density of beta-adrenoceptor binding sites were unaffected by the lesion. It is suggested that the recognition sites of the different receptor populations surviving the lesion most likely reside on homologous and/or heterologous nerve terminals.

Animals↗
PubMed1983

Mode of action of gamma-butyrolactone on the central cholinergic system.

Gamma-butylactone (GBL), a drug depressing the central nervous system, produced marked increases in acetylcholine contents in rat brain hemispheric regions (striatum, hippocampus, cortex) and in striatal choline content without modifying choline acetyltransferase or acetylcholinesterase activities. In the hippocampus GBL also strongly decreased the acetylcholine turnover rate and inhibited the high affinity uptake of choline. Its increase in acetylcholine content was prevented by an acute electrolytic lesion of the medial septum but not by a wide array of drug treatments designed to interfere with neurotransmission in various pathways. The results are taken to indicate that GBL directly depresses the cholinergic septal-hippocampal afferents by interrupting impulse flow. In the striatum, too, GBL markedly depressed the acetylcholine synthesis rate but had no effect on the high affinity choline uptake process. Such dissociation of the two phenomena had previously been observed using other drugs and may denote that acetylcholine synthesis in this region is regulated differently from that in the hippocampus. By comparison, gamma-hydroxybutyric acid (GHBA), an active metabolite which shares with GBL the capacity to produce a somnolent state and depress impulse flow in the dopaminergic nigroneostriatal pathway, had no effect on either striatal acetylcholine content or on hippocampal high affinity choline uptake. The results suggest that GBL can be distinguished from GHBA in its neuropharmacological central cholinergic effects.

4-Butyrolactone↗
PubMed1982

Effect of dimethylamino-2-ethoxyimino-2-adamantane (CM 54903), a non-polar dimethylaminoethanol analog, on brain regional cholinergic neurochemical parameters.

CM 54903, a new psychotropic drug with a particular pharmacological profile, produced a widespread but short-lasting decrease in acetylcholine content in rat brain hemispheric regions but not in the midbrain-hindbrain or cerebellum at the dose of 40 mg/kg, i.p. The decrease was most conspicuous in the striatum. Brian regional choline contents were unaltered as were the acetylcholine turnover rates in the striatum and hippocampus. Neither choline acetyltransferase nor acetylcholinesterase activities were altered after the in vitro incubation or the in vivo administration of high amounts of the drug. CM 54903 was found to be a competitive, reversible inhibitor of the sodium-dependent high affinity uptake of choline by crude hippocampal and striatal synaptosomal preparations showing an IC50 of 10 microM in vitro. Despite the fact that the drug readily crosses the blood-brain barrier and achieves brain concentrations several-fold greater than its in vitro IC50, CM 54903 did not inhibit choline uptake in vivo although it was capable of preventing the pentylenetetrazol-stimulated choline uptake by hippocampal synaptosomes. The changes in striatal acetylcholine content induced by the blockade or the stimulation of muscarinic cholinergic receptors or dopaminergic receptors did not interfere with the effect of CM 54903 on striatal acetylcholine content while pentylenetetrazol completely prevented the decrease. The results taken together indicate that the major effect of CM 54903 on the cholinergic neurons is at the presynaptic level to compete with choline at its uptake sites.

Acetylcholine↗
PubMed1982

Modulation of the hippocampal alpha-adrenoceptor population by lesion of the serotonergic raphe-hippocampal pathway in rats.

Electrolytic lesion of the ascending serotonergic fibers in the median raphe nucleus or in both the median raphe nucleus and dorsal raphe nucleus caused after 18 days more than 80% depletion of serotonin in the hippocampus and frontal cortex, respectively, without affecting norepinephrine and acetylcholine contents. alpha 1-Adrenoceptor binding of (3H) WB-4104 was increased in the hippocampus but not in the frontal cortex. Scatchard analysis revealed that the increase in (3H) WB-4101 binding in the lesioned hippocampus was the result of an elevated density of alpha 1-adrenergic receptors of about 65%. This phenomenon began 8 days postlesion and persisted for at least 90 days postlesion. Similar qualitative and quantitative results were obtained following chemical lesion of the serotonergic cells of origin in the median raphe nucleus with 5,7-dihydroxytryptamine. Selectivity of the phenomenon was further demonstrated as or beta-adrenoceptor binding with (3H) dihydroalprenolol and cholinergic muscarinic receptor binding with (3H) dexetimide were not significantly affected in the hippocampus. By comparison, when norepinephrine in the hippocampus was depleted by more than 90% by bilateral lesion of the ascending noradrenergic fibers with 6-hydroxydopamine (18 days), the alpha 1-adrenoceptor number was significantly increased by only about 20% while the beta-adrenoceptor number was enhance by 40%. The area-selective increase in alpha 1-adrenoceptor number in the hippocampus in the presence of unchanged norepinephrine content and in the absence of serotonin probably signifies that serotonin actively participates in the modulation of the noradrenergic receptor population.

Animals↗
PubMed1982

Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system.

Buspirone, a novel psychotropic anxioselective agent, produced a dose-dependent decrease in the level of acetylcholine in the striatum of the rat. The maximum effect of about 25-30% was produced at the dose of 20 mg kg-1. A smaller decrease of 10% was also found in the n. accumbens-olfactory tubercle while other brain regions were unaffected. The drug did not alter striatal choline acetyltransferase or acetylcholinesterase activities and was feeble in displacing [3H]dexetimide from its specific muscarinic binding sites. The effect of buspirone in lowering acetylcholine content was more marked and longer lasting in the striatum of female than male rats. Buspirone proved to be weak as a blocker of the dopamine receptor agonist, apomorphine, and it appears that only a small proportion of the decrease in striatal acetylcholine content can be attributed to the blockade of dopamine receptors. Rapid homologous tolerance to an acute challenge with buspirone on striatal acetylcholine was achieved within seven days of its chronic administration, and, unlike clozapine, a cross tolerance of buspirone to chronic haloperidol treatment was also observed. Other data indicating that the drug differed from haloperidol both qualitatively and quantitatively on dopaminergic neurochemical parameters, and the fact that it is not cataleptogenic, suggest that buspirone cannot be considered a typical neuroleptic agent. The possibility that buspirone may act as an agonist at certain presynaptic dopamine receptors, which could translate into a fall in striatal acetylcholine content, is discussed.

Acetylcholine↗
PubMed1981

Studies on the indirect feedback inhibition of cholinergic neurons triggered by oxotremorine in striatum.

Oxotremorine produced 30-75% increases in rat striatal acetylcholine content and 10-15% decreases in choline content at the subtremorogenic doses of 0.34-1.34 mumol/kg, without affecting choline acetyltransferase and acetylcholinesterase activities and the sodium-dependent high affinity uptake of choline. The increase in acetylcholine was blocked by atropine and by reserpine indicating that oxotremorine indirectly influences the intrinsic striatal cholinergic neurons through a monoamine-mediated negative feedback loop. Experiments designed to interfere with neurotransmitter function indicated that noradrenaline and not dopamine or serotonin, mediated the response to oxotremorine.

Acetylcholine↗
PubMed1980

Comparison of the effects of the stereoisomers of fenfluramine on the acetylcholine content of rat striatum, hippocampus and nucleus accumbens.

The (+)- and (-)- isomeric forms of fenfluramine were compared for their effects on rat brain area acetylcholine (ACh) content. The drugs showed similar patterns in increasing ACh content in the accumbens and hippocampus and in being ineffective in the brainstem. The actions differed in the striatum where the (+)-form markedly increased ACh content while the (-)-form produced no change. Both isomer-induced increases in ACh in the accumbens were prevented when 5-HT synthesis was blocked by p-chlorophenylalanine, thus denoting 5-hydroxytryptaminergic mediation of these effects. In striatum, the increase in ACh induced by (+)-fenfluramine was summated with the increase in ACh induced by dopamine receptor stimulation with apomorphine and was not prevented by dopamine receptor blockade with pimozide. On the other hand, apomorphine's effect was blocked by (-)-fenfluramine while pimozide pretreatment unmasked an increase in ACh induced by (-)-fenfluramine. The results favour the notion that there is a population of cholinergic neurons intrinsic to the striatum which is under inhibitory 5-HT regulation and independent of inhibitory dopamine regulation.

Acetylcholine↗
PubMed1978

Storage and release of acetylcholine in the isolated superior cervical ganglion of the rat.

The storage and release of acetylcholine and choline were studied in the isolated superior cervical ganglion of the rat by a radioenzymic method. The acetylcholine and choline contents were 202.2 +/- 5.1 and 624.7 +/- 20.2 pmole/ganglion, respectively. The transmitter tissue store was unaffected during 1 h of superfusion in choline--Krebs solution, while a 20% decrease was exhibited after 2 h and then remained approximately stable. Conversely, choline content declined to 50% within 1 h and further to 37% of the original level by 4 h. About 24% of the choline assayed in the intact preparation is located in the connective sheath. Preganglionic nerve stimulation at 10--20/sec or potassium stimulation (40 mM KCl) invariably decreased the transmitter tissue stores by 25--45%; such a depletion is independent of the presence or absence of external choline. By contrast, the presence of choline proved to be a prerequisite for the efficient release of acetylcholine from eserinized ganglia during continuous 10/sex stimulation. A drastic depression in the acetylcholine release is described which is related to the time of preincubation of the ganglia with eserine prior to stimulation. Indeed, a 30 min exposure to eserine, compared with a 5 min period, resulted in a 4-fold decrease in the steady output rate. Under optimal conditions, the initial volley output at 10/sec was 1.3 X 10(-4) of the releasable transmitter pool and 1.9 X 10(-4) during the steady-state output. These results are discussed in the light of the electrophysiological knowledge of the quantal release process at the ganglionic synapse.

Acetylcholine↗