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.

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).

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.

Visualization of growth factor receptor sites in rat forebrain.

It is now known that various growth factors may also act in the central nervous system. Among them, it has recently been shown that epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) may possess trophic effects in the mammalian brain. We report here on the respective autoradiographic distribution of [125I]EGF and [125I]IGF-I receptor binding sites in the rat brain, both during ontogeny and in adulthood.

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.

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.

Autoradiographic distribution of multiple classes of opioid receptor binding sites in human forebrain.

Receptor binding parameters and autoradiographic distribution of various opioid receptor sites have been investigated in normal human brain, post-mortem. [3H]DAGO, a highly selective mu ligand, binds to a single class of high affinity (Kd = 1.1 nM), low capacity (Bmax = 160 fmol/mg protein) sites in membrane preparations of frontal cortex.

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.

Localization of kappa opioid receptor binding sites in human forebrain using [3H]U69,593: comparison with [3H]bremazocine.

1. The autoradiographic distribution of kappa opioid receptor binding sites in human brain was examined using two radiolabeled probes, namely [3H]U69,593 and [3H]bremazocine. 2.

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.

Effect of quinolinic acid in the nucleus basalis magnocellularis on cortical high-affinity choline uptake.

A transient 45% increase in cortical high-affinity choline uptake (HACU) was observed after an injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM) of the rat. This was followed by a steady decline in choline uptake, which resulted in a 46% decrease by day 7. Specific [3H]hemicholinium-3 binding to coronal brain sections showed a similar pattern following injections of QUIN into the nbM.

[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.

Structure-activity studies of C- and N-terminal fragments of cholecystokinin 26-33 in guinea pig isolated tissues.

In vitro structure-activity studies with cholecystokinin (CCK)/gastrin-related peptides, including C- and N-terminal fragments of CCK 26-33, were undertaken in guinea pig gallbladder and ileum. The general order of potency in both smooth muscle preparations is CCK 26-33 greater than CCK 1-33 greater than 27-33 much much greater than nonsulfated (NS) CCK 26-33 greater than pentagastrin greater than CCK 30-33. None of the CCK fragments exhibit antagonistic properties such as in guinea pig, rat and mouse pancreatic acinar cells and hog duodenum.

Localization of cholecystokinin receptors in relation to the nigrostriatal and mesolimbic dopaminergic pathways.

The anatomical distribution of cholecystokinin (CCK)-dopamine (DA) neurons suggests that CCK could modulate dopaminergic activity. To further investigate that hypothesis, the cellular localization of CCK receptors was ascertained in relation to mesolimbic and nigrostriatal DA pathways after a series of chemical lesions induced with ibotenic acid and 6-hydroxydopamine. The results suggest that CCK receptors are not localized on dopaminergic neurons of the nigrostriatal and mesolimbic pathways.

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.

Autoradiographic distribution of non-dopaminergic binding sites labeled by [3H]haloperidol in rat brain.

The regional distribution of binding sites labeled by [3H]haloperidol, in the presence of excess spiroperidol, was compared to the regional distribution of receptors labeled by [3H]SCH 23390 and [3H]sulpiride, [3H]SCH 23390 and [3H]sulpiride labeled distinct nuclei, such as the olfactory tubercle, caudate, globus pallidus, substantia nigra, and inferior and superior colliculi. In contrast, the distribution of binding sites labeled by [3H]haloperidol, in the presence of excess spiroperidol, were much more extensive. Some areas containing the highest density of sites labeled by [3H]haloperidol were the external plexiform layer of the olfactory bulb, the cerebral cortex, the paraventricular nuclei, the interpeduncular nucleus and the superior colliculus.

Platelet imipramine binding in patients with panic disorder and major familial depression.

Platelet 3H-imipramine binding was investigated in 15 normal subjects, 17 patients with major depressive disorder and 43 patients with panic disorder, to further study the relationship between depressive and anxiety disorders. Whereas patients with major depression had a significantly lower mean Bmax value than healthy volunteers, mean Bmax values in patients with panic disorder did not differ significantly from normal controls. Furthermore, apparently normal Bmax values were observed even in those panic disorder patients who had concurrent major depression or a past history of depression.

Effect of apomorphine on melatonin secretion in normal subjects.

There is some evidence in animals that dopamine (DA) affects melatonin secretion. The effect of apomorphine (Apo), a selective DA receptor agonist, and placebo on day-time melatonin secretion was studied in six normal men. Apo HCl in a dose (0.

Differential effects of selective lesions of cholinergic and dopaminergic neurons on serotonin-type 1 receptors in rat brain.

Serotonin (5-HT)-type1 (abbreviated as a subscript 1) receptor binding sites are discretely distributed in rat brain. High densities of [3H]5-HT1 binding sites are especially located in areas enriched with cholinergic and dopaminergic innervation, such as the substantia innominata/ventral pallidum, striatum, septal nuclei, hippocampus and substantia nigra. The possible association of [3H]5-HT1 binding sites with cholinergic or dopaminergic cell bodies and/or nerve fiber terminals was investigated by selective lesions of the substantia innominata/ventral pallidum-cortical and septohippocampal cholinergic pathways and the nigrostriatal dopaminergic projection.

Characterization and autoradiographic distribution of hemicholinium-3 high-affinity choline uptake sites in mammalian brain.

[3H]hemicholinium-3 (HC-3) binding characteristics have been investigated using membrane binding assays and in vitro receptor autoradiography. In rat brain membrane preparations, [3H]HC-3 binds with high affinity to an apparent single class of sites. [3H]HC-3 binding is Na+-dependent.

Human brain receptor autoradiography using whole hemisphere sections: a general method that minimizes tissue artefacts.

A general method for the preparation of high-quality, mostly ice-crystal-artefact-free whole human brain hemisphere sections is described. Upon receipt, hemispheres are divided; one is then fixed in buffered 10% formalin for neuropathological analysis while the other is cut in 8-10-mm-thick coronal slices that are then rapidly frozen in 2-methylbutane at -40 degrees C (10-15 sec) before being placed in the brain bank at -80 degrees C. Such rapid freezing markedly decreases the formation of ice-crystal artefacts.

Neurotensin receptor binding sites in monkey and human brain: autoradiographic distribution and effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment.

Neurotensin (NT) receptor binding sites were characterized and localized by using membrane binding assay and in vitro receptor autoradiography in monkey and human brain. Additionally, the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment on NT binding sites were investigated in monkey. [125I]Tyr3-NT ([125I]NT) apparently binds to a single class of high-affinity sites (Kd in nanomolar range) in both species.