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J Traber

Publications and source records attributed to J Traber.

At least 37 records · Page 2Linked to original sources
PubMed1990

Cortical projection patterns of the medial septum-diagonal band complex.

A detailed analysis of the cortical projections of the medial septum-diagonal band (MS/DB) complex was carried out by means of anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). The tracer was injected iontophoretically into cell groups of the medial septum (MS) and the vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and sections were processed immunohistochemically for the intra-axonally transported PHA-L. The labeled efferents showed remarkable differences in regional distribution in the cortical mantle dependent on the position of the injection site in the MS/DB complex, revealing a topographic organization of the MS/DB-cortical projection. In brief, the lateral and intermediate aspects of the HDB, also referred to as the magnocellular preoptic area, predominantly project to the olfactory nuclei and the lateral entorhinal cortex. The medial part of the HDB and adjacent caudal (angular) part of the VDB are characterized by widespread, abundant projections to medial mesolimbic, occipital, and lateral entorhinal cortices, olfactory bulb, and dorsal aspects of the subicular and hippocampal areas. Projections from the rostromedial part of the VDB and from the MS are preponderantly aimed at the entire hippocampal and retrohippocampal regions and to a lesser degree at the medial mesolimbic cortex. Furthermore, the MS projections are subject to a clear mediolateral topographic arrangement, such that the lateral MS predominantly projects to the ventral/temporal aspects of the subicular complex and hippocampus and to the medial portion of the entorhinal cortex, whereas more medially located cells in the MS innervate more septal/dorsal parts of the hippocampal and subicular areas and more lateral parts of the entorhinal cortex. PHA-L filled axons have been observed to course through a number of pathways, i.e., the fimbria-fornix system, supracallosal stria, olfactory peduncle, and lateral piriform route (the latter two mainly by the HDB and caudal VDB). Generally, labeled projections were distributed throughout all cortical layers, although clear patterns of lamination were present in several target areas. The richly branching fibers were abundantly provided with both "boutons en passant" and terminal boutons. Both distribution and morphology of the labeled basal forebrain efferents in the prefrontal, cingulate, and occipital cortices closely resemble the distribution and morphology of the cholinergic innervation as revealed by immunohistochemical demonstration of choline acetyltransferase. In contrast, the labeled projections to the olfactory, hippocampal, subicular, and entorhinal areas showed a heterogeneous morphology. Here, the distribution of only the thin varicose projections resembled the distribution of cholinergic fibers.

Animals↗
PubMed1990

The behavioural responses to 8-OH-DPAT, ipsapirone and the novel 5-HT1A receptor agonist Bay Vq 7813 in the pig.

In pigs, behavioural responses were examined after administration of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a full agonist at 5-hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype, and the pyrimidinylpiperazine derivatives ipsapirone and Bay Vq 7813 (2-[4-(2-pyrimidinyl)-1-piperazinylpropyl]-1,2-benzisothiazol++ +-3(2H) one-1,1-dioxide), which act as partial agonists at 5-HT1A receptors. The most prominent behavioural response examined after 8-OH-DPAT, 0.5 mg/kg i.m., ipsapirone, 2-5 mg/kg i.m., and Bay Vq 7813, 0.5-2 mg/kg i.m. or i.v., were head shakes. The potency of the three drugs to induce this behaviour correlated with their activity at 5-HT1A receptors as determined by inhibition of forskolin-stimulated adenylate cyclase, substantiating that the head shake response has potential as a quantitative probe of in vivo receptor function. The 5-HT2/5-HT1C receptor antagonist ritanserin did not counteract the head shakes induced by ipsapirone, suggesting that neither 5-HT2 nor 5-HT1C receptors are involved in mediation of this response to this 5-HT1A receptor agonist in pigs. Once daily administration of Bay Vq 7813 or ipsapirone for 3-5 days led to a reduction in the head shake response. 1-Pyrimidinylpiperazine (1-PP), a pharmacologically active metabolite shared by ipsapirone, Bay Vq 7813, and related pyrimidinylpiperazine derivatives, did not induce behavioural alterations in pigs. The data provide further evidence that marked species differences exist in functional responses to 5-HT receptor ligands.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

A new method for quenching correction leads to revisions of data in receptor autoradiography.

Differential quenching of beta-emission affects strongly the analysis of receptor distribution patterns in quantitative receptor autoradiography with tritiated ligands. Different methods for the quenching correction have been described in the past, but some of these are of limited value, if a detailed anatomical parcellation is necessary. Other methods correct exclusively local variations in lipid concentration, which is an important, but only one of several factors causing quenching. A new method for the measurement of quenching (or autoradiographic efficiency) is presented, which permits an anatomically detailed and direct determination of the total quenching without lipid extraction procedures. This method is based on the measurement of autoradiographic efficiency in cryostat sections homogeneously labeled with tritiated formaldehyde by an underlying gelatine section containing this labeled compound. Regional and layer specific measurements of autoradiographic efficiency in cortical and subcortical regions of the human and rat brain are reported. A significant correlation was found between the density of myelin and autoradiographic efficiency but other factors were also shown to influence differential quenching. The use of the here presented correction procedure leads to revisions of the laminar distribution patterns reported for different receptors in human and rat cortical areas. Our results show, that a complete quenching correction is necessary for the mapping of receptor distributions with tritiated ligands.

Animals↗
PubMed1990

ACTH-induced behaviors and their modulation by serotonergic agonists differ in neonatal and weanling rat pups.

Four-day-old (P4) and 21-22-day-old (P21-22) rat pups received an intracisternal injection of either ACTH1-16NH2 or saline followed by a subcutaneous (SC) injection of saline, the serotonergic (5HT)1A agonists 8-OH-DPAT or ipsapirone, the 5HT1B agonist TFMPP or the 5HT2 agonist DOI. The ontogeny of ACTH-induced behaviors including grooming, yawn and stretch as well as various serotonin-related behaviors were recorded via time-sampling at 20 s intervals for a test duration of 50 min. ACTH induced slight but significant increases in grooming at P4, along with a significant increase in yawning. At this age the 5HT1B agonist TFMPP induced substantial increases in grooming, with no effect of the other agonists on this behavior. All of the serotonergic agonists, however, decreased ACTH-induced yawning at P4. At P21-22 ACTH induced more robust grooming than that observed at P4, although different in nature from adult-typical ACTH-induced grooming. This ACTH-induced grooming at P21-22 was attenuated by all of the serotonergic agonists. ACTH-induced yawning at P21-22 was not affected by the serotonergic agonists while ACTH-induced stretching was increased by the 5HT1B agonist TFMPP at this age. These data provide additional evidence of differential mediation of various ACTH-induced behaviors, and support other reports of ontogenetic alterations in the response to serotonergic manipulations during the neonatal to weanling age period.

Adrenocorticotropic Hormone↗
PubMed1990

Effects of the 1,4-dihydropyridine-sensitive L-type calcium channel antagonist nimodipine and calcium channel activator Bay K 8644 on local cerebral glucose utilization in the rat.

The quantitative [14C]-2-deoxy-D-glucose autoradiographic method was used to compare the acute effects of the Ca2+ channel antagonist nimodipine (10 mg/kg) and the Ca2+ channel activator Bay K 8644 (1.25 mg/kg) on local cerebral glucose utilization of rat brain after single, intraperitoneal application. Nimodipine reduced glucose metabolism significantly in 23 of the 49 brain regions evaluated. Bay K 8644 decreased the local cerebral glucose utilization to an even greater extent in all regions studied. The anatomic localization of those regions with the largest decrease of glucose utilization was almost identical for both drugs (globus pallidus, hippocampus, geniculate body, substantia nigra, and entorhinal cortex). No increase in glucose metabolism was measured in any of the brain areas evaluated.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

CNS and PNS effects of nimodipine.

Calcium ions play a decisive role in a large number of processes dealing with development, regeneration after damage, and aging of elements of the nervous system. Nimodipine, a member of the 1,4-dihydropyridine chess of calcium-channel blockers, has proved to influence the calcium metabolism of neurons. This review focuses on the results of recent studies on the role of nimodipine in both the central and peripheral nervous system, during or after events that threaten the integrity or function of the nervous system.

Aging↗
PubMed1990

Effects of 5-hydroxytryptamine1A-receptor agonists on hippocampal damage after transient forebrain ischemia in the Mongolian gerbil.

The activation of 5-hydroxytryptamine receptors exerts an inhibitory influence on neuronal activity in a way similar to the activation gamma-amino-n-butyric acid and adenosine A1 receptors. Therefore, we hypothesized that 5-HT1A-receptor agonists might exert a neuroprotective effect. We tested the full agonists Bay R 1531 and 8-OH-DPAT and the partial agonists ipsapirone and gepirone in the model of transient global ischemia in the Mongolian gerbil. Ipsapirone protected 53% of pyramidal neurons (p less than 0.05) in the CA1 area of the hippocampus from ischemic damage at a dose of 3 mg/kg. Bay R 1531 showed a powerful neuroprotective effect with 100% preservation of neurons at a dose of 3 mg/kg (p less than 0.001) while gepirone and 8-OH-DPAT were ineffective. These findings suggest that 5-HT1A-receptor agonists might be effective tools for the therapy of cerebral ischemia. However, the varying results indicate that transient forebrain ischemia in the gerbil may not be the optimal model system to demonstrate clearly the neuroprotective activity of these compounds.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Demonstration of muscarinic acetylcholine receptor-like immunoreactivity in the rat forebrain and upper brainstem.

The distribution of muscarinic acetylcholine receptor protein (mAChR) in the rat forebrain and upper brainstem was described by using a monoclonal antibody (M35) raised against mAChR purified from bovine forebrain homogenates. A method is investigated for light microscopic (LM) and electronmicroscopic (EM) immunocytochemical visualization of reactivity to mAChR-proteins. Putative cholinoceptive neurons including their dendrites were found immunoreactive in the cortical mantle, hippocampus, basal ganglia, amygdala, thalamus and several midbrain regions. In the neocortex, immunoprecipitate with M35 was mainly present in layer 5 pyramidal cells, some layer 3 pyramidal neurons and layer 2 stellate cells, all including their characteristic dendritic profiles of both basal and apical dendrites. In the hippocampus, a variety of pyramidal, granular and non-pyramidal celltypes were stained in various hippocampal cell layers, in the dentate hilus and in stratum oriens of cornu ammonis. Moreover, positively reacting cells occurred in central and lateral amygdala, all parts of the basal ganglia and ventral pallidum. The thalamus was very richly provided with labeled neurons in several nuclei but notably numerous in the ventrolateral, anteroventral and geniculate nuclei. In cortex and hippocampus also some staining of astrocytes occurred. Electron microscopic study of the intracellular distribution of M35 immunoreactivity in all cases showed dense precipitates in the soma cytoplasm in close association with the golgi apparatus, but conspicuous absence near the endoplasmic reticulum. Immunoprecipitate can be followed within the dendritic tree along the microtubular transport system, up to proximal and distal postsynaptic membrane positions, apposing non labeled presynaptic endings. Muscarinic receptor subtype recognition by M35 will be discussed by comparing M35 distribution with cholinergic innervation patterns, muscarinic receptor ligand binding studies and localization of muscarinic receptor subtype mRNAs.

Animals↗
PubMed1989

Pharmacological basis for the use of nimodipine in central nervous system disorders.

Nimodipine, a Ca2+ antagonist with cerebrovasodilatory and anti-ischemic effects, binds to rat, guinea pig, and human brain membranes with high affinity (less than 1 nM). Only at higher concentrations has nimodipine been reported to block the release of some neurotransmitters and hormones from neuronal tissue. Nimodipine has no consistent effect on brain oxygen consumption or cortical ATP or phosphocreatine levels, although the ischemia-induced fall of brain ATP levels in gerbils or the lowering of intracellular brain pH in rabbits with focal cerebral ischemia were antagonized by the drug. In rats and baboons with middle cerebral artery occlusion, nimodipine was found to reduce neurological deficits without an increase in intracranial pressure or brain edema. Electrophysiological studies with nimodipine suggested a direct neuronal action. In rabbit dorsal root ganglion cells, concentrations as low as 20 nM were reported to block inward Ca2+ currents. Recent studies have suggested that nimodipine may also improve memory in brain-damaged or old rats, restore sensorimotor function and abnormal walking patterns of old rats, and accelerate acquisition of associative learning in aging rabbits. Blockade of age-related changes in Ca2+ fluxes in rat hippocampal neurones by nimodipine in vitro pointed to neuronal plasma membrane as the site of nimodipine action. The therapeutic usefulness of nimodipine appears not to be limited to cerebral ischemia, but may include dementia, age-related degenerative diseases, epilepsy, and ethanol intoxication.

Aging↗
PubMed1988

GTP effects in rat brain slices support the non-interconvertability of M1 and M2 muscarinic acetylcholine receptors.

GTP (guanosine-5'-triphosphate) markedly reduced high-affinity 3H-oxotremorine-M binding to M2 receptors on brain slices in autoradiographic experiments while 3H-pirenzepine binding to M1 receptors was largely unaffected. The distribution of M1 receptors so labelled was also not altered by GTP to include former M2-rich regions, thus indicating that GTP could not, by itself, interconvert high agonist-affinity M2 receptors to M1 receptors.

Animals↗
PubMed1987

Oral administration of nimodipine accelerates functional recovery following peripheral nerve damage in the rat.

Oral administration of the Ca2+-entry blocker nimodipine accelerates in a dose-dependent manner the recovery of sensorimotor function following a crush lesion of the rat sciatic nerve. The beneficial effect of nimodipine was apparent in both a foot shock withdrawal test and in a test analyzing the walking pattern of the rat. These data are the first demonstration of nimodipine-induced enhanced recovery following peripheral nerve damage.

Administration, Oral↗
PubMed1987

Effect of the 5-HT1A receptor agonist ipsapirone on the local cerebral glucose utilization of the rat hippocampus.

Local cerebral glucose utilization (LCGU) was measured in the hippocampus of the rat brain following i.p. injection of the anxiolytic drug and 5-HT1A receptor agonist ipsapirone (TVX Q 7821). Administration of ipsapirone (5 mg/kg) reduced glucose utilization in the various hippocampal areas to variable extent. The most subtle reduction took place in the dorsal subiculum, while the most pronounced decrease was found in sector CA4 of Ammon's horn. The degree of LCGU reduction can be related to the 5-HT1A receptor density in the respective areas.

Animals↗
PubMed1987

Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transported Phaseolus vulgaris leucoagglutinin.

The present paper deals with a detailed analysis of cortical projections from the magnocellular basal nucleus (MBN) and horizontal limb of the diagonal band of Broca (HDB) in the rat. The MBN and HDB were injected iontophoretically with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). After immunocytochemical visualization of labeled efferents, the distribution of projections over the cortical mantle, olfactory regions and amygdala were studied by light microscopy. Based on differences in cortical projection patterns, the MBN was subdivided in anterior, intermediate and posterior portions (MBNa, MBNi and MBNp). All subdivisions maintain neocortical projections and are subject to an anterior to posterior topographic arrangement. In the overall pattern, however, the frontal cortex is the chief target. Furthermore, all MBN parts project to various regions of meso- and allocortex, which are progressively more dense when the tracer injection is more anteriorly placed. The most conspicuous finding, however, was a ventrolateral to dorsomedial cortical projection pattern as the PHA-L injection site moved from posterior to anterior. Thus, the posterior MBN projects predominantly to lateral neo- and mesocortex while the anterior MBN sends more fibers to the medial cortical regions. Furthermore, the MBNa is a source of considerable afferent input to the olfactory nuclei and as such should be regarded as a transition to the HDB. The HDB, apart from projecting densely to olfactory bulb and related nuclei, maintains a substantial output to the medial prefrontal cortical regions and entorhinal cortex, as well. Comparison of young vs aged cases indicate that aging does not appear to have a profound influence on cortical innervation patterns, at least as studied with the PHA-L method.

Acetylcholinesterase↗
PubMed1987

Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N,N-dimethyltryptamine.

Male Wistar rats were trained to discriminate the interoceptive effects of 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT; 1.25 mg/kg, IP) from saline in a two-lever operant chamber. Following discrimination learning, the following drugs (with ED50 dose in mg/kg IP) dose-dependently generalized: lysergic acid diethylamide (LSD, 0.04), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.11), 6-methoxy-4-(dipropyl-amino)-1,3,4,5-tetrahydrobenz(c,d)indole hydrochloride (BAY R 1531, 0.15), 5-OMe-DMT itself (0.63), ipsapirone (TVX Q 7821, 2.7), and buspirone (3.8). The potencies of these drugs in generalization tests were best correlated with their binding affinities for the 5-HT1A serotonin receptor subtype (as measured by displacement of 3H-ipsapirone in the hippocampus). Drugs not, or only partially generalizing included quipazine, bufotenin, m-trifluoromethylphenylpiperazine (TFMPP), 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole succinate (RU 24969), citalopram, clomipramine, 1,4-dihydro-2,6-dimethyl-3-nitro-4(2-trifluoromethylphenyl)-pyridine-5- carboxylate (BAY K 8644), the buspirone metabolite 1-pyrimidinyl-piperazine (1-PP), methysergide, metergoline, and metitepine. Of the last three compounds with antagonistic activity at 5-HT receptors, as well as ketanserin, pizotifen, and ritanserin, only metitepine and pindolol could fully block the 5-OMe-DMT stimulus. Pizotifen blocked the generalization of quipazine fully, that of 5-OMe-DMT only partially, and that of ipsapirone not at all. These data indicate that the 5-HT1A receptor subtype is strongly involved in the transduction of the interoceptive discriminative stimuli induced by 5-OMe-DMT, with 5-HT2 agonism also playing a possible role.

Animals↗