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Biomedical subjects

R Quirion

Publications and source records attributed to R Quirion.

At least 307 records · Page 17Linked to original sources
PubMed1988

The effects of chronic antidepressant treatment in an animal model of anxiety.

We have examined the anxiolytic activity of acute and chronic antidepressant treatment in an animal model of anxiety involving novelty-suppressed feeding. Rats were food deprived for 48 h, placed into a novel environment containing food, and the latency to begin eating was recorded. Chronic (21 days), but not acute injections of desipramine (DMI; 10 mg/kg) and amitriptyline (AMI; 10 mg/kg) significantly reduced the latency to begin eating compared to controls, but the percentage decrease was not as great as that seen with either acute or chronic treatment with diazepam (2 mg/kg) or adinazolam (20 mg/kg). A time course study indicated that at least 2 weeks of treatment was necessary to observe a significant anxiolytic effect of antidepressants. The anxiolytic effect of the antidepressants was specific to the novel environment, as 2 weeks of treatment with either diazepam or DMI did not influence the latency to begin eating in the home cage. Finally, a single dose of the central benzodiazepine receptor antagonist, Ro15-1788 (20 mg/kg), given 15 min prior to testing, did not block the anxiolytic effects of chronic DMI, while it completely eliminated the effect of chronic diazepam treatment. These data suggest that antidepressants acquire anxiolytic properties following chronic administration and that this effect appears to be independent of the benzodiazepine receptor system.

Amitriptyline↗
PubMed1988

Evidence for increased amyloid enhancing factor activity in Alzheimer brain extract.

Soluble brain extracts containing 0.1 to 16 mg of protein from 3 normal human brain and 11 patients with Alzheimer's disease, Down's syndrome and other neurological disorders were assayed for amyloid enhancing factor (AEF) activity in the mouse bioassay. At the 0.1 mg dosage, five of seven brain extracts from amyloid-positive samples and only one of four amyloid-negative samples demonstrated AEF activity. Marginal AEF activity was detected in the normal brain extracts at 8 or 16 mg protein dosage. Alzheimer-AEF was aggregated by exhaustive dialysis against 0.01 M phosphate buffer, pH 6 or distilled water and the solubilized aggregate was fractionated on a BioGel P-60 column. Of the two protein peaks, AEF activity was present only in the low mol.wt second fraction, which on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining showed two discrete and three minor peptide bands between 60 and 66 kDa and one of these was periodic acid-Schiff positive, and three fuzzy bands near 14 kDa. Pretreatment of the crude and second fraction with 10 mM phenylmethylsulfonyl fluoride (PMSF) nearly completely abolished the in vivo AEF bioactivity. It is suggested that (a) a higher AEF concentration is present in amyloid-positive brain samples than those negative for amyloid or normal brain tissues, (b) AEF-positive fraction contains at least five dominant peptides ranging between 14 to 66 kDa, and (c) abolition of PMSF-treated Alzheimer-AEF activity, similar to that of murine AEF, might be due to its serine/thiol proteinase nature. To our knowledge, this is the first time that AEF activity has been demonstrated in Alzheimer brain samples.

Adult↗
PubMed1988

Decreased density of peripheral benzodiazepine binding sites on platelets of currently drinking, but not abstinent alcoholics.

Using the isoquinoline carboxamide derivative, PK 11195 as selective ligand, the binding properties of peripheral benzodiazepine binding sites were compared on platelets of alcoholics and non-alcoholic, healthy controls. When compared to controls, alcoholics during prolonged ethanol consumption show a significant reduction in the density of platelet [3H]PK 11195 binding sites. However, following abstention from alcohol, the density of these sites is similar to controls. These data suggest that a reduction in the density of peripheral benzodiazepine binding sites on platelets may be a biochemical index of prolonged ethanol use and indicate a possible role for these sites in mediating the chronic effects of alcohol.

Adult↗
PubMed1988

Comparative distribution of neuropeptide Y immunoreactivity and receptor autoradiography in rat forebrain.

The distributions of neuropeptide Y (NPY) and NPY receptors in rat brain have been compared. High densities of NPY-like fibers and terminals are present in the hypothalamus and the endopiriform nucleus with corresponding low densities of NPY receptor binding sites. Conversely, low densities of fibers and terminals are observed in the thalamus, stria terminalis and hippocampus with corresponding high densities of binding sites. Various hypotheses are discussed to explain those apparent mismatches including the existence of other classes of receptors and possible paracrine actions of NPY-like peptides in the brain.

Animals↗
PubMed1988

Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer's disease.

The main objective of the present study was to determine whether cholinergic markers (choline acetyltransferase activity and nicotinic and muscarinic receptors) are altered in Alzheimer's disease. Choline acetyltransferase activity in Alzheimer's brains was markedly reduced in various cortical areas, in the hippocampus, and in the nucleus basalis of Meynert. The maximal density of nicotinic sites, measured using the novel nicotinic radioligand N-[3H]methylcarbamylcholine, was decreased in cortical areas and hippocampus but not in subcortical regions. M1 muscarinic cholinergic receptor sites were assessed using [3H]pirenzepine as a selective ligand; [3H]pirenzepine binding parameters were not altered in most cortical and subcortical structures, although the density of sites was modestly increased in the hippocampus and striatum. Finally, M2-like muscarinic sites were studied using [3H]-acetylcholine, under muscarinic conditions. In contrast to M1 muscarinic sites, the maximal density of M2-like muscarinic sites was markedly reduced in all cortical areas and hippocampus but was not altered in subcortical structures. These findings reveal an apparently selective alteration in the densities of putative nicotinic and muscarinic M2, but not M1, receptor sites in cortical areas and in the hippocampus in Alzheimer's disease.

Acetylcholine↗
PubMed1988

Characterization of N-[3H]methylcarbamylcholine binding sites and effect of N-methylcarbamylcholine on acetylcholine release in rat brain.

The present experiments show that N-[3H]-methylcarbamylcholine ([3H]MCC) binds specifically and with high affinity to rat hippocampus, frontal cortex, and striatum. The highest maximal density of binding sites was apparent in frontal cortex and the lowest in hippocampus. [3H]MCC binding was potently inhibited by nicotinic, but not muscarinic, agonists and by the nicotinic antagonist dihydro-beta-erythroidine in all three brain regions studied. The effect of unlabeled MCC on acetylcholine (ACh) release from slices of rat brain was tested. The drug significantly enhanced spontaneous ACh release from slices of hippocampus and frontal cortex, but not from striatal slices. This effect of MCC to increase ACh release from rat hippocampus and frontal cortex was antagonized by the nicotinic antagonists dihydro-beta-erythroidine and d-tubocurarine, but not by alpha-bungarotoxin or by the muscarinic antagonist atropine. The MCC-induced increase in spontaneous ACh release from hippocampal and frontal cortical slices was not affected by tetrodotoxin. The results suggest that MCC might alter cholinergic transmission in rat brain by a direct activation of presynaptic nicotinic receptors on the cholinergic terminals. That this alteration of ACh release is apparent in hippocampus and frontal cortex, but not in striatum, suggests that there may be a regional specificity in the regulation of ACh by nicotinic receptors in rat brain.

Acetylcholine↗
PubMed1988

Characterization, distribution and plasticity of atrial natriuretic factor binding sites in brain.

The [125I]iodotyrosyl derivative of atrial natriuretic factor [( 125I])ANF) apparently binds to a single class of high affinity sites in guinea pig brain membrane preparations. Ligand selectivity pattern reveals that the structural requirements of brain [125I]ANF binding sites are similar to those reported in most peripheral tissues. In vitro receptor autoradiographic studies demonstrate that the brain distribution of [125I]ANF binding sites is species dependent. In rat, high levels of binding are found in olfactory bulb, subfornical organ, area postrema, choroid plexus, and ependyma. In guinea pig, these regions are also enriched with [125I]ANF binding in addition to various thalamic nucleic, amygdala, hippocampus, and cerebellum. In monkey, high densities of sites are seen in the cerebellar cortex. This suggests that brain ANF receptor sites could mediate ANF effects related to the central integration of cardiovascular parameters, as well as other actions not associated with these systems. As in the periphery, it appears that brain [125I]ANF binding sites are associated with guanylate cyclase. Moreover, the density of [125I]ANF receptor binding sites is altered in certain brain regions in spontaneously hypertensive rats and in cardiomyopathic hamsters, demonstrating the plasticity of brain ANF receptors. Thus, ANF and ANF receptors are complementary facets of a new neurotransmitter-neuromodulator system present in mammalian brain.

Animals↗
PubMed1988

Neurobehavioral effects of intrathecal somatostatinergic treatment in subhuman primates.

We infused somatostatin and its long-acting analogue (SMS 201-995) into the intracranial subarachnoid space of eight monkeys. Chronic infusions of SMS 201-995 produced marked neurotoxic effects characterized by truncal ataxia, dysmetria, and severe bradykinesia, with normal level of consciousness. Subcutaneous injection of apomorphine, a dopaminergic agonist, promptly reversed these effects. Further studies are required before intrathecal somatostatin replacement therapy can be offered to patients with Alzheimer's disease.

Animals↗
PubMed1988

Effect of hydrocortisone on basal and apomorphine-induced growth hormone secretion in normal subjects.

The effect of hydrocortisone (HC) (200 mg, i.v. over 15 min) on the growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine HCl (Apo) (0.5 mg sc), and on basal prolactin (PRL) secretion was studied in 11 normal male volunteers. In addition, the effect of HC on 3H-spiperone binding to rat striatal membranes was investigated. HC alone increased basal GH secretion compared with placebo (p less than 0.02) commencing 90 min after injection (p less than 0.05). When HC was given before Apo the GH response to Apo was blunted (p less than 0.05), and the delayed HC-induced increase was absent (p less than 0.001). HC or Apo alone had no effect on PRL secretion but HC plus Apo significantly decreased PRL concentrations compared with placebo (p less than 0.01) or HC alone (p less than 0.001). HC (0.1-100 microM) had no effect on 3H-spiperone binding in vitro. The mechanisms involved in the effect of HC on GH and PRL are unclear. The ability of HC to both stimulate and antagonize GH secretion points to multiple sites of action within the hypothalamic-pituitary axis.

Adult↗
PubMed1987

Apparent molecular weight of substance P/neurokinin-1 receptors determined using a photoaffinity labelled probe, [(3'-125I) D-Tyro, (4'-N3)Phe8, Nle11]-substance P.

A photoreactive derivative, [(3'-125I) D-Tyro, (4'-N3)Phe8, Nle11]-substance P (SP) was prepared and iodinated using carrier-free [125I] to determine the apparent molecular weight of one sub-type of neurokinin (NK) receptor, the SP/NK-1 type. The unlabelled analogue competed for [3H]-SP sites with an IC50 of 10 nM. The radioactive photoprobe (KD approximately 0.17 nM, Bmax = 15.6 fmol/mg protein) was used to photoaffinity label membranes prepared from rat brain. Autoradiographs revealed that a single band with an apparent molecular weight of 46,000 daltons was specifically labelled. This labelling was inhibited by non-radioactive SP in a concentration-dependent manner (1.0 nM-0.1 mM) suggesting that the observed labelling represents the SP/NK-1 receptor type.

Affinity Labels↗
PubMed1987

Postnatal handling reduces novelty-induced fear and increases [3H]flunitrazepam binding in rat brain.

Postnatal handling of rat pups alters their response to novelty. We have now shown that, as adults, rats handled for the first three weeks of life showed a suppression of feeding in a novel environment that was less, and a [3H]flunitrazepam binding in whole brain that was greater than in non-handled animals. These data suggest that variations in benzodiazepam binding capacity could be related to individual differences in the fear response to novelty.

Animals↗
PubMed1987

Opioid receptor subtypes associated with ventral tegmental facilitation and periaqueductal gray inhibition of feeding.

Eating was induced in sated animals by lateral hypothalamic electrical stimulation following central microinjections of mu- (morphine), delta-([D-Pen2,D-Pen5]enkephalin) or kappa-(U-50,488H) receptor agonists, or saline. With stimulation intensity fixed at a moderate level, time to eat 3 45-mg food pellets decreased with increases in stimulation frequency, approaching an asymptote near 7 s at ca. 70 Hz. Ventral tegmental injections (8 but not 0.8 nmol) of each of the 3 drugs reduced the minimum frequency required to produce eating of 3 pellets within 20 s and reduced the frequency at which asymptotic performance was produced; the drugs were equally effective at these doses. Naloxone (2 mg/kg) reversed the effects of each drug; naloxone was slightly more effective against morphine than against DPDPE or U-50,488H. These data suggest that all 3 receptor classes may contribute to the ventral tegmental facilitation of feeding. Periaqueductal gray injections (16 but not 1.6 nmol) of morphine had the opposite effect; they increased the stimulation frequency required to cause eating of 3 pellets in 20 s, and decreased the speed of eating across all stimulation frequencies. Periaqueductal gray injections of the delta- and kappa-agonists were each without effect. These data indicate that the periaqueductal gray inhibition of feeding is mediated solely by mu-receptors and their associated periaqueductal gray circuitry.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Comparison of [125I]Bolton-Hunter neuropeptide Y binding sites in the forebrain of various mammalian species.

The forebrain distribution of [125I]Bolton-Hunter (BH) neuropeptide Y (NPY) binding sites was compared in 4 mammalian species including rat, hamster, guinea pig and monkey. In all species studied, high densities of [125I]BH NPY binding sites were observed in the hippocampus. In this structure, [125I]BH NPY binding sites were distributed in a laminar fashion, with high densities seen in the oriens layer and stratum radiatum. However, species differences were seen in certain brain areas such as striatum, septum, thalamus and hypothalamus. These differences should be taken into account when studying central effects of neuropeptide Y.

Animals↗
PubMed1987

[3H]N-methyl-carbamylcholine, a new radioligand specific for nicotinic acetylcholine receptors in brain.

The present study characterized the binding of [3H]N-methyl-carbamylcholine ([3H]methyl-carbachol), a new radioligand, to rat cerebral cortex membranes and demonstrated the autoradiographic distribution of these sites in rat brain. With atropine used to block muscarinic acetylcholine sites and nicotine to define non-specific binding, [3H]methyl-carbachol bound specifically, saturably and with high affinity (Kd = 11.0 nM, Bmax = 118.4 fmol/mg protein and Hill coefficient = 0.92) to a population of presumably nicotinic sites in cerebral cortex membranes. When nicotine was used to block nicotinic acetylcholine sites and atropine to define non-specific binding there was no specific binding of [3H]methyl-carbachol (concentrations up to 45 nM) to possible muscarinic sites in cerebral cortex membranes. The binding parameters under non-selective conditions (without blockade of either muscarinic or nicotinic acetylcholine sites) had very similar values to those obtained under nicotinic conditions (Kd = 8.0 nM, Bmax = 125.0 fmol/mg protein and Hill coefficient = 0.98). [3H]Methyl-carbachol binding was potently inhibited by nicotinic agonists and antagonists but only poorly displaced by muscarinic agents. Autoradiographic studies evidenced high densities of [3H]methyl-carbachol binding sites in the interpeduncular nucleus, various thalamic nuclei, superior colliculus and layers III/IV of the cortex. Such a distribution was very similar to those previously reported for nicotinic acetylcholine sites and other radioligands. These results suggest that [3H]methyl-carbachol is a specific radioligand of the neuronal nicotinic receptor. Its stability and high selectivity constitute distinct advantages over previously used nicotinic radioligands such as acetylcholine and nicotine.

Animals↗
PubMed1987

Coexistence of central and peripheral benzodiazepine binding sites in the human pineal gland.

The pineal gland and particularly its major hormone, melatonin, may participate in several physiological functions, including sleep promotion, anticonvulsant activity and the modulation of biological rhythms and affective disorders. These effects may be related to an interaction with benzodiazepine receptors, which have been demonstrated to be present in the pineal gland of several species including man. The present study examined the characteristics of benzodiazepine binding site subtypes in the human pineal gland, using [3H]flunitrazepam and [3H]PK 11195 as specific ligands for central and peripheral type benzodiazepine binding sites respectively. Scatchard analysis of [3H]flunitrazepam binding to pineal membrane preparations was linear, indicating the presence of a single population of sites. Clonazepam and RO 15-1788, which have a high affinity for central benzodiazepine binding sites, were potent competitors for [3H]flunitrazepam binding in the human pineal, whereas RO 5-4864 had a low affinity for these sites. Analyses of [3H]PK 11195 binding to pineal membranes also revealed the presence of a single population of sites. RO 5-4864, a specific ligand for peripheral benzodiazepine binding sites was the most potent of the drugs tested in displacing [3H]PK 11195, whereas clonazepam and RO 15-1788 were weak inhibitors of [3H]PK 11195 binding to pineal membranes. Overall, these results demonstrate, for the first time, the coexistence of peripheral and central benzodiazepine binding sites in the human pineal gland.

Aged↗