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R Bertorelli

Publications and source records attributed to R Bertorelli.

13 recordsLinked to original sources
PubMed1992

Effect of tianeptine on the central cholinergic system: involvement of serotonin.

The effect of tianeptine on in vivo acetylcholine (ACh) release from brain hemispheric regions of freely moving rats was investigated using the microdialysis technique coupled with a sensitive radioenzymatic method. Tianeptine, at the dose of 30 mg/kg i.p., reduced ACh release from dorsal hippocampi by 40% in 40 min, and induced a 30% decrease of ACh output from frontal cortices while at the doses of 10 and 20 mg/kg it had no effect. In striata the drug did not significantly affect ACh release although it showed a tendency to increase it. The ACh content in the three areas considered was not affected by tianeptine at above doses. The drug did not alter choline-o-acetyltransferase and acetylcholinesterase activities suggesting that it did not influence the cholinergic system through direct action on the ACh metabolism; furthermore, it did not influence the sodium-dependent high-affinity uptake of choline in striatum, cortex and hippocampus. Impairment of serotonergic (5-HT) neurotransmission by chemical lesion of the median raphe nucleus or by metergoline, a blocker of 5-HT receptors, antagonized the cholinergic effect of tianeptine. The involvement of the serotonergic system is specific because lesions of the noradrenergic dorsal bundle failed to prevent the inhibitory action of tianeptine. The present data suggest that 5-HT may mediate the effect of tianeptine on the cholinergic system in dorsal hippocampi.

Acetylcholine↗
PubMed1992

Dopamine depletion preferentially impairs D1- over D2-receptor regulation of striatal in vivo acetylcholine release.

The roles of D2 and D1 dopaminergic receptors on the regulation of striatal acetylcholine (ACh) release in vivo were examined for a period of 120 min after acute (2 h) or prolonged (16 h) depletion of brain dopamine (DA) by alpha-methyl-p-tyrosine. The reduction of DA transmission did not affect basal ACh output after 2 h but markedly lowered ACh release by 16 h (50%). Acute alpha-methyl-p-tyrosine pretreatment prevented the reduction of ACh release by the D1 antagonist SCH 23390 and its increase by the D2 antagonist, remoxipride, consistent with a drastic reduction of DA transmission at both DA receptors. However, 16 h after alpha-methyl-p-tyrosine, the effect of remoxipride on ACh release was restored, but SCH 23390 still had no effect, suggesting that the D2 inhibitory tone on ACh release had recovered, whereas the reduction of the D1 facilitatory influence persisted. The D1 facilitatory control of ACh neurotransmission thus appears to be more sensitive than the D2 inhibitory control to a reduction in DA transmission. The new model of DA-ACh interaction resulting from these data casts fresh light on the relationship between changes in DA transmission and extrapyramidal motor function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord.

The 20-amino acid peptide M-15 binds with high affinity (IC50 approximately 0.1 nM) to 125I-labeled galanin (125I-GAL) binding sites in membranes from the ventral hippocampus, midbrain, and rat spinal cord. Receptor autoradiographic studies show that M-15 can displace 125I-GAL from all labeled sites. M-15 acts as a reversible high-affinity antagonist in blocking the inhibitory effects of GAL on the evoked release of acetylcholine in vivo in the hippocampus and on the GAL-induced hyperpolarization of locus coeruleus neurons in slices. M-15 also blocks the facilitatory effects of GAL on the spinal flexor reflex. Thus, the chimeric peptide M-15 [GAL-(1-13)-substance P-(5-11)amide] represents the first antagonist to the neuronal actions of GAL.

Acetylcholine↗
PubMed1991

Modulation of cortical in vivo acetylcholine release by the basal nuclear complex: role of the pontomesencephalic tegmental area.

Acetylcholine (ACh) release in vivo from rat cortices was determined by microdialysis either after injection of drugs into the basal nuclear complex (NBM) or after electrolytic lesion of the pontomesencephalic tegmental nucleus (PPT). Scopolamine (SCOP) (5-10 micrograms) increased and oxotremorine (10 micrograms) reduced cortical ACh release, indicating that an inhibitory mechanism operates within the area. The gamma-aminobutyric acid (GABA)ergic antagonist, picrotoxin (2.5 micrograms), by disinhibiting the cholinergic basocortical neurons, induced an increase that was not affected by SCOP. Acute lesion of the cholinergic PPT efferents to NBM raised cortical basal release. Thus, ACh released from the PPT terminals apparently modulates the function of basocortical neurons mainly through a polysynaptic link via GABAergic neurons.

Acetylcholine↗
PubMed1991

Pertussis toxin-sensitive G-protein mediates galanin's inhibition of scopolamine-evoked acetylcholine release in vivo and carbachol-stimulated phosphoinositide turnover in rat ventral hippocampus.

The effects of intracerebroventricular (i.c.v.) injections of pertussis toxin were investigated on the inhibitory action of galanin on acetylcholine release and phosphoinositide breakdown stimulated by muscarinic agents in rat ventral hippocampus. Pertussis toxin (0.6 micrograms, i.c.v., 96 h) counteracted the in vitro inhibitory effect of galanin (3.1 nmol) on phosphoinositide breakdown stimulated by carbachol without altering the stimulatory action of the cholinergic agonist on signal transduction, in miniprisms from rat ventral hippocampus. Pertussis toxin also abolished the in vivo effect of galanin on scopolamine-stimulated acetylcholine release in vivo but did not affect basal acetylcholine release. The results indicate that pertussis toxin-sensitive G-protein(s) mediates the galanin receptor regulation of pre- and postsynaptic cholinergic functions in the ventral hippocampus.

Acetylcholine↗
PubMed1990

Anaesthesia effects on in vivo acetylcholine transmission; comparisons of radioenzymatic and HPLC assays.

The effect of general anaesthesia on extracellular levels of acetylcholine (ACh) in the caudate-putamen of freely moving rats was studied by microdialysis. ACh concentrations were determined in the same perfusate samples by radioenzymatic and HPLC/electrochemical procedures in order to compare the assays. The concentration of ACh in perfusate samples was estimated to be 0.30 microM in conscious unrestrained rats. However, when these rats were administered chloral hydrate (400 mg/kg i.p.), the level of ACh was decreased immediately by 50%, attaining a value of 0.06 microM within 20-40 min following the injection. Upon recovery of the righting reflex, ACh levels were once again re-elevated. The levels of choline (Ch), the precursor of ACh, were unaffected by anaesthesia. It was apparent that the level of consciousness (i.e. awake vs. anaesthetized) is an important factor determining ACh overflow. Radioenzymatic and HPLC assays proved to give identical results for the analysis of ACh and Ch.

Acetylcholine↗
PubMed1990

Cholinergic neurons of the pontomesencephalic tegmentum release acetylcholine in the basal nuclear complex of freely moving rats.

Two major systems of cholinergic projection neurons are found within the centrum of the mammalian brain: the basal nuclear complex, projecting predominantly to the cerebral cortex, amygdala, and hippocampus, and the pontomesencephalotegmental network, innervating primarily the thalamus. Neurons comprising the latter network also project to the basal forebrain, but the functional properties of that fiber connection, if any, are unknown. In an attempt to address this issue, the extracellular concentration of acetylcholine was measured in the basal nuclear complex of freely moving rats, both singularly and in combination with lesions and pharmacologic manipulations. Acetylcholine release monitored in the presence of physostigmine sulfate in the basal forebrain was (a) calcium-dependent, (b) increased by systemic scopolamine injection, the rise persisting in the presence of quisqualate lesions of the basal nuclear complex, (c) blocked by tetrodotoxin, and (d) abolished by ablation of cell bodies in the pontomesencephalic tegmentum, which also produced a decrease of choline acetyltransferase activity in the nucleus basalis/substantia innominata region, but not by quisqualate lesions of the basal forebrain. It is concluded from these data that the calcium-dependent release of acetylcholine in the basal nuclear complex (a) is largely axonal in nature, (b) derives substantially from axons of the cholinergic pontomesencephalic tegmentum, and (c) appears to be controlled by presynaptic muscarinic receptors on axon terminals of the latter system. The pontomesencephalotegmental cholinergic complex might thus influence cortical acetylcholine release, in part at least, by means of serial-order cholinergic-cholinergic interactions in the basal nuclear complex.

Acetylcholine↗
PubMed1990

D1 and D2 dopaminergic regulation of acetylcholine release from striata of freely moving rats.

The effects of selective D1 and D2 dopaminergic agents on the extracellular acetylcholine (ACh) content in striata of freely moving rats were determined by the microdialysis technique. LY 171555, a selective D2 agonist, reduced ACh output by approximately 30% within 20 min at the dose of 0.2 mg/kg, i.p., whereas the D2 antagonists (-)-remoxipride (10 mg/kg, s.c.) and L-sulpiride (50 mg/kg, i.p.) induced maximal increases of approximately 50% within 10 and 20 min, respectively. In contrast, the D1 antagonist SCH 23390 (0.25 mg/kg, s.c.) decreased the extracellular ACh content by approximately 30% in 20 min, but lower doses--0.025 and 0.05 mg/kg--had no such effect. The stimulation of ACh release by LY 171555 was prevented by (-)-remoxipride but not by SCH 23390 (0.25 mg/kg, s.c.). In addition, the D1 agonist SKF 38393 failed to modify the ACh increasing effect of (-)-remoxipride. Thus, the D1 and D2 receptors subserve opposing functions on ACh release. The D1/D2 dopaminergic agonist R-apomorphine, at the does of 1 mg/kg, i.p., reduced ACh output by approximately 35% only when D1 receptors were blocked by SCH 23390 (0.025 mg/kg, s.c.). The results provide clear in vivo evidence of the tonic inhibition exerted by dopaminergic nigrostriatal input on the cholinergic system of the basal ganglia through D1 and D2 receptors.

Acetylcholine↗
PubMed1989

Effects of the l isomer of fenfluramine on dopamine mechanisms in rat brain: further studies.

Experiments were carried out to gain additional evidence that l-fenfluramine reduces the dopamine-mediated effects in intact animals. l-Fenfluramine 5 and 10 mg/kg i.p. dose dependently raised the levels of homovanillic acid in the striatum and nucleus accumbens of rats 1 h after injection. The effect of 5 mg/kg l-fenfluramine disappeared and was actually reversed 4 and 8 h after injection. The effect of 10 mg/kg l-fenfluramine, administered 48 h after the last haloperidol dose, was completely antagonized in both striatum and nucleus accumbens of animals made tolerant to the effect of haloperidol on homovanillic acid levels (through repeated treatment with 1 mg/kg haloperidol i.p. twice daily for 11 days). Unlike haloperidol (0.25 mg/kg), l-fenfluramine in various doses (2.5-20 mg/kg i.p.) did not modify the levels of striatal 3-methoxytyramine or change the decrease induced by a s.c. injection of 0.5 mg/kg apomorphine. The effect of apomorphine was not antagonized by 10 or 20 mg/kg l-norfenfluramine, an active metabolite of l-fenfluramine but 20 mg/kg l-norfenfluramine significantly raised striatal 3-methoxytyramine levels. l-Fenfluramine 20 mg/kg (but not 10 mg/kg) significantly enhanced the output of striatal acetylcholine assessed by trans-striatal microdialysis, for 60 min after injection. Apomorphine 1 mg/kg i.p. completely antagonized the increase of acetylcholine caused by 1 mg/kg haloperidol or 20 mg/kg l-fenfluramine. The results confirm that the l isomer of fenfluramine produces effects on the responses to dopamine and acetylcholine similar to those of neuroleptics by a mechanism not involving direct blockade of receptors.

Animals↗
PubMed1989

N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor.

The galanin N-terminal fragment [galanin-(1-16)] has been prepared by solid-phase synthesis and by enzymic cleavage of galanin by endoproteinase Asp-N. This peptide fragment displaced 125I-labeled galanin in receptor autoradiography experiments on rat forebrain and spinal cord and in equilibrium binding experiments from high-affinity binding sites in the ventral hippocampus with an IC50 of approximately 3 nM. In tissue slices of the same brain area, galanin-(1-16), similarly to galanin, inhibited the muscarinic agonist-stimulated breakdown of inositol phospholipids. Upon intracerebroventricular administration, galanin-(1-16) (10 micrograms/15 microliters) also inhibited the scopolamine (0.3 mg/kg, s.c.)-evoked release of acetylcholine, as studied in vivo by microdialysis. Substitution of [L-Trp2] for [D-Trp2] resulted in a 500-fold loss in affinity as compared with galanin-(1-16). It is concluded that, in the ventral hippocampus, the N-terminal galanin fragment [galanin-(1-16)] is recognized by the galanin receptors controlling acetylcholine release and muscarinic agonist-stimulated inositol phospholipid breakdown as a high-affinity agonist and that amino acid residue [Trp2] plays an important role in the receptor-ligand interactions.

Animals↗
PubMedDate not supplied

Decrease of brain acetylcholine release in aging freely-moving rats detected by microdialysis.

In vivo extracellular acetylcholine release from brain hemispheric areas of 2-, 9-, and 18-month-old rats was measured by intracerebral microdialysis coupled with a radioenzymatic assay. Dialysis tubing was inserted transversally through both striata, frontal cortices and dorsal hippocampi 24 hours before the experiments. In the 2-month-old rats, the net average acetylcholine output, corrected for recovery and expressed in fmoles/min/single striatum, cortex and hippocampus, was 902.4 +/- 67, 303.9 +/- 14 and 334 +/- 32, respectively. In 18-month-old rats acetylcholine output was 53, 35 and 37% lower in striatum, cortex and hippocampus, respectively, than in young rats. The release from the striatum in the 9-month-old was intermediate between those of the 2- and 18-month-old rats. The intracerebroventricular injection of hemicholinium-3 caused a marked decrease in acetylcholine release from the striata of 2- and 18-month-old rats. If the decrease with hemicholinium was expressed as percent of the basal release there was no age-related difference between the young and old rats, indicating that the differences observed were due to the lower basal release found in the old rats. The possibility that the deficit in basal acetylcholine release with age may depend on a reduction of acetylcholine synthesis is discussed.

Acetylcholine↗
PubMedDate not supplied

Acute and chronic studies on functional aspects of coexistence.

Autoinhibition of acetylcholine release by the coexisting peptide galanin in the septal afferents to the hippocampus of the rat was examined in tissue slices from the hippocampus. Galanin inhibits the evoked release of the coexisting neurotransmitter, acetylcholine, in the ventral hippocampus, providing an example of autoinhibition of release of a neurotransmitter by one of the coexisting neurotransmitters. The galanin mediated inhibition of the acetylcholine release is a complement to the well known strong cholinergic autoinhibition. The effects of the coexisting galanin and acetylcholine on several second messenger systems were also examined: acetylcholine acting at muscarinic receptors depresses cyclic adenosine 3',5'-monophosphate and stimulates elevation of cyclic guanosine 3',5'-monophosphate levels, whereas neither cyclic adenosine 3',5'-monophosphate nor cyclic guanosine 3',5'-monophosphate levels were affected by galanin (1 microM). Galanin however inhibited partly the muscarinic stimulation of phosphoinositide breakdown, suggesting that inositol phosphate(s) or diacylglycerol may act as second messenger(s) of the galanin action in the hippocampus. The effects of chronic changes in firing rate on the coexisting neurotransmitters in the rat ventral spinal cord containing serotonin, thyrotropin releasing hormone, substance P and substance K were examined. The tissue levels of the coexisting transmitters were studied in rats chronically treated with imipramine (14 days; 2 x 10 mumoles/kg/day) and zimelidine (14 days; 2 x 10 mumoles/kg/day). Upon treatment with zimelidine the tissue levels of the serotonin metabolite 5-hydroxyindoleacetic acid fall by 32% while thyrotropin releasing hormone levels seem to increase 35% and substance P/substance K levels also increase 48 and 72% respectively. Imipramine treatment resulted in similar although less pronounced changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗