PubMed Health⌕ Search

Biomedical subjects

B M Spruijt

Publications and source records attributed to B M Spruijt.

At least 73 records · Page 4Linked to original sources
PubMed1992

Effects of the ACTH4-9 analog Org2766 on brain plasticity: modulation of excitatory neurotransmission?

ACTH-like neuropeptides have been investigated in various paradigms such as cognition, neuronal damage and neuronal excitation. All their effects may be collectively described as modulation of neural plasticity. However, the mechanism of action accounting for these effects remains to be demonstrated. This report is an overview of the data and has incorporated some additional findings of the influence of the ACTH4-9 analog, Org2766, on neuronal excitation, especially in the hippocampus. An interaction with NMDA receptors may account for the various aspects of plasticity. Based on recent findings demonstrating that the ACTH4-9 analog counteracts both the NMDA antagonist, AP5, and NMDA-induced explosive running behavior, the hypothesis is put forward that glutamatergic neurotransmission is involved in behavioral changes induced by the ACTH4-9 analog.

Adrenocorticotropic Hormone↗
PubMed1991

Behavioral and anatomical consequences of unilateral fornix lesions and the administration of nimodipine.

Male Wistar rats subjected to unilateral fimbria-fornix transection by mechanical knife cut or to sham operations were tested in a water maze and in an open field. Half the animals in each group were treated with either 0.06 mg/kg nimodipine or vehicle, administered i.p. for 7 days, beginning the day of surgery. Animals were sacrificed and brains were processed for acetylcholine esterase (AChE) histochemistry. In the water maze, lesioned rats showed a significant impairment relative to the sham-operated animals. Nimodipine treatment did not improve performance. There were no differences among the groups in the observed frequencies of the open field behaviors of locomotion, hole-poke, rearing and grooming. A significant reduction of AChE-positive cell bodies was found in the medial septal region on the side of the lesion. There were no differences in water maze performance among groups of rats treated with 0.0, 0.5, 1.0, or 5.0 mg/kg nimodipine for 7 days, beginning the day of fimbria-fornix transection, in an attempt to determine any dose-dependent effect of the drug.

Acetylcholinesterase↗
PubMed1991

Quantitation of the growth-associated protein B-50/GAP-43 and neurite outgrowth in PC12 cells.

A combined assay to measure neurite outgrowth and B-50/GAP-43 levels in PC12 cells is reported. During NGF-induced neuritogenesis, B-50/GAP-43 expression was monitored by enzyme-linked immunosorbent assay (ELISA). Neurite outgrowth was quantified at the same time by the use of video image analysis. Sensitivity and reliability of the methods are shown with a dose-response and time curve of beta-NGF-induced neuritogenesis. A linear increase in total length of neurites was induced by concentrations of beta-NGF greater than or equal to 5 ng/ml and was accompanied by a linear increase in the amount of B-50/GAP-43. The combined methods presented here can conveniently and reliably establish subtle changes in neurite outgrowth and intracellular protein contents.

Adrenal Gland Neoplasms↗
PubMed1991

Effect of Org2766, an ACTH(4-9) analogue, on recovery after bilateral transection of the fimbria fornix in the rat.

Facilitation of recovery after peripheral or central damage of the nervous system induced by neuropeptides was recently extensively reported. In a previous study we reported that Org2766, an ACTH(4-9) analogue, enhances recovery as assessed in a spatial orientation task after unilateral transection of the fimbria fornix in the rat. It was suggested that cross-lateral compensation by the intact fimbria fornix hippocampal system could account for the peptide-induced recovery. Therefore, the facilitatory effect of this neuropeptide was investigated in the present study after bilateral transection of the fimbria fornix. The present results indicate that Org2766 also attenuated the behavioral deficit of bilaterally transected animals in a spatial learning task, but does not affect behaviour of the lesioned animals in a passive avoidance test.

Adrenocorticotropic Hormone↗
PubMed1989

Aging and sociosexual behavior in the male rat.

Senescent and young rats have been studied in a copulatory test and sociosexual approach test. The copulatory test was applied to investigate age-dependent changes in the copulatory capacity in the rat. The sociosexual approach test was used to describe motivational aspects of this behavior. Latencies, frequencies and durations of copulatory behaviors in the copulatory test and visits to various incentive animals in the approach test have been measured. Senescent rats had longer latencies and less frequencies of copulatory behaviors. In the approach test they showed less visits to the estrous female. Data were also subjected to a correlational analysis in order to relate the findings of the two tests. It is concluded that aged male rats differ from young ones in organizing their behavior in relation to time, are less social and have a less pronounced social preference pattern. In addition, the coherence between various elements of copulatory behavior was less in the senescent rat than in the young male rat, whereas the social approach patterns are more coherent in the aged male.

Aging↗
PubMed1988

Molecular transduction mechanisms in ACTH-induced grooming.

Intraventricular administration of ACTH1-24 induces excessive grooming in the rat. Ethogram analysis shows that the peptide does not alter grooming behavior seen in a novel box, but that it prolongs the duration of the grooming bout. Extensive structure-activity studies have been performed which suggest that the active site lies in a region (5-13) of the ACTH molecule. Interestingly, the (1-24) sequence is fully active, whereas (1-10) and (11-24) alone or in combination are inactive, pointing to a specific stereoconformation necessary to induce grooming. However, despite the fact that there are ACTH-and/or alpha-MSH-containing peptidergic neurons, no conclusive evidence is available demonstrating stereospecific, saturable binding sites for these peptides in brain. The analysis of the neural substrate underlying ACTH-induced excessive grooming has been performed by means of electrolytic lesions of specific brain regions and by neuropharmacological manipulations. The data suggest that the periaqueductal gray is the primary target for ACTH and that the activity of neostriatum and accumbens, via a nigro-colliculus-periaqueductal gray pathway, modulates the display of excessive grooming. An important feature of the neural substrate is that it displays single-dose tolerance to the peptide during the first hours after the first peptide injection. It is suggested that the tolerance is a feature of an opioid receptor-containing component of the neural substrate. The molecular mechanism of action of ACTH is complex and may involve different transmembrane signal transduction systems. The peptide decreases the degree of phosphorylation of a neuron-specific, synaptic phosphoprotein B-50 by inhibition of protein kinase C. It is concluded that changes in the degree of phosphorylation of B-50 regulate the activity of the lipid kinase phosphatidylinositol 4-phosphate kinase. Therefore, the B-50 protein seems to be part of a negative feedback loop in the receptor-activated hydrolysis of phosphatidylinositol 4,5-bis-phosphate (PIP2). There is increasing evidence that the molecular mechanism by which ACTH brings about the grooming response involves a change in phosphorylation of B-50. Firstly, the structure-activity relationship of ACTH-induced excessive grooming is nearly identical to that obtained for ACTH-induced inhibition of protein kinase C.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1986

The colliculus superior modulates ACTH-induced excessive grooming.

In previous studies the involvement of nigrostriatal dopaminergic activity in ACTH(1-24)-induced grooming has been established. It was suggested that the dopaminergic modulation of ACTH(1-24)-induced excessive grooming is exerted through the striato-nigro-collicular pathway. To obtain further evidence it was investigated, whether local application of GABAergic agents into the colliculus superior modulates excessive grooming occurring after an intraventricular injection with ACTH(1-24). It appeared that intra-collicular picrotoxin (a GABAergic antagonist) suppressed ACTH-induced grooming, whereas muscimol (a GABAergic agonist) enhanced the grooming response. The picrotoxin-induced R(unning) F(it) B(ehavior), elicited from the colliculus superior was also seen after intraventricular administration of picrotoxin. A detailed comparison of this behavioral response seen after both routes of administration of picrotoxin suggests that intraventricularly injected picrotoxin may well induce the RFB via a direct effect on the colliculus superior. Lesions placed in the colliculus superior completely abolished picrotoxin-induced RFB, exploration and orientation behavior. Yet, these lesions did not reduce excessive grooming suggesting that although this region may be involved in the modulation of ACTH-induced grooming it is not the primary site of peptide action.

Adrenocorticotropic Hormone↗
PubMed1986

Dopaminergic modulation of ACTH-induced grooming.

ACTH-(1-24)-induced grooming was studied after administration of the peptide into the substantia nigra or intracerebroventricularly (i.c.v.). The modulation of dopamine receptors in neostriatum (with haloperidol and apomorphine) and nucleus accumbens (with 3,4-dihydroxyphenylamino-2-imidazoline hydrochloride; DPI and ergometrine) was investigated. In the nucleus accumbens, the modulatory effects of ergometrine and DPI on ACTH-(1-24)-induced grooming were based on their affinity for dopamine receptors and not on their affinity for adrenoceptors. Intrastriatal application of dopaminergic agents inhibited i.c.v. ACTH-(1-24)-induced excessive grooming, whereas the grooming score was enhanced if ACTH-(1-24) was administered into the substantia nigra. The finding of differential effects of dopaminergic agents on ACTH-induced excessive grooming depending on the route of administration indicate that i.c.v. ACTH-induced excessive grooming is not mediated solely through the substantia nigra. The increase in grooming behavior seen after the intrastriatal administration of dopaminergic agents - when ACTH was injected into the substantia nigra - suggests the involvement of the striato-nigral GABAergic pathway. Local injections of ACTH-(1-24) into the periaqueductal gray also induced excessive grooming. Since a second injection of ACTH-(1-24) into the periaqueductal gray did not lead to a grooming response, irrespective of where the first injection of ACTH-(1-24) was given (i.c.v. into the nigra or via the periaqueductal gray) it is suggested that this structure seems to play a primary role in the induction of excessive grooming. Therefore the modulatory effects of the dopaminergic influence on ACTH-(1-24)-induced grooming may be exerted via the striato-nigro-collicular pathway.

Adrenocorticotropic Hormone↗
PubMed1986

The periaqueductal gray: a prerequisite for ACTH-induced excessive grooming.

The periaqueductal gray is known to be involved in the expression of a variety of behaviours such as aggression, beta-endorphin-induced immobility and peptide-induced excessive grooming. In order to establish whether the periaqueductal gray (PAG) is indispensible for peptide-induced excessive grooming, lesions were placed in the dorsal part of this structure. Subsequently, the grooming-inducing abilities of adrenocorticotropin (ACTH), beta-endorphin and bombesin were tested. The lesioned animals did not display excessive grooming after intracerebroventricular injection of ACTH. beta-Endorphin administration into the lesioned animals resulted in an extreme display of immobility. Local injection of bombesin into the PAG resulted in reduced scratching behaviour followed by immobility. It was hypothesized that excessive grooming (elicited by ACTH) may be mediated through a non-opioid primary target site-situated in the lesioned region of the PAG-while excessive scratching and immobility (elicited by bombesin or beta-endorphin, respectively) may be mediated through an opioid primary target site (situated in the remaining part of the PAG). Furthermore, the analysis of social behaviour of lesioned animals revealed that these animals reacted towards an unfamiliar partner predominantly with freezing behaviour. The increase of beta-endorphin-induced immobility and socially induced freezing (which is morphologically very similar to beta-endorphin-induced immobility) in lesioned animals supports the hypothesis that the release of opioid peptides such as beta-endorphin in the PAG plays a role in the regulation of social behaviour.

Adrenocorticotropic Hormone↗
PubMed1986

Melanocortins, neural plasticity and aging.

Peptides derived from ACHT and alpha-MSH are known to exert trophic influences on peripheral and central nervous structures. Age-related brain diseases may in part be related to loss of neural plasticity. Melanocortins improve adaptional abilities of the nervous system. Chronic treatment with melanocortins may counteract age-related brain pathology.

Adrenocorticotropic Hormone↗
PubMed1986

The influence of neurotensin, naloxone, and haloperidol on elements of excessive grooming behavior induced by ACTH.

Naloxone, haloperidol, and neurotensin suppress ACTH-induced grooming. The suppressive effects of naloxone and of haloperidol on ACTH-induced grooming are observed following subcutaneous as well as intracerebroventricular administration. The suppression of ACTH-induced grooming by these drugs is not accompanied by a change in the relative distribution of grooming elements. From previous data and from the results of the present study it is suggested that the underlying substrate involved in ACTH-induced excessive grooming may differ from that of bombesin-induced grooming.

Adrenocorticotropic Hormone↗
PubMed1985

Effects of ACTH1-24 on male rat behavior in an exploratory, copulatory and socio-sexual approach test.

The effect of intraventricular application of ACTH1-24 on exploratory behavior, excessive grooming, and socio-sexual behavior in male rats was studied. It appeared that ACTH1-24 (1 microgram/animal) affects both excessive grooming and exploration. Sexual performance was delayed, as expressed in latency time to ejaculation, probably because of prolonged grooming behavior. The behavioral effects of ACTH are explained in terms of enhanced attention to external stimuli.

Adrenocorticotropic Hormone↗
PubMed1984

Behavioral sequences as an easily quantifiable parameter in experimental studies.

In behavioral pharmacology frequencies and/or durations of postures are used as easily quantifiable parameters. However, significant information is also contained in the sequential order of the different behavioral elements; structural changes in behavior are not necessarily reflected in the totals of durations and frequencies. Furthermore, observed changes in these parameters might be better understood if the change in structure is known. Presently, parameters for sequences are barely used, probably because they require larger groups of animals and more sophisticated computer programs. In this paper a procedure, using a simple set of computer programs (see Appendices), is demonstrated for transformation of behavioral sequences into transition matrices, including a procedure for creating the minimal number of transitions required for further statistical analysis.

Adrenocorticotropic Hormone↗
PubMed1983

Prolonged animal observation by use of digitized videodisplays.

Quantitative assessment of animal behavior requires not only much time and good training, but is always dependent upon the interpretation of the observer. Therefore we employed a commonly-used microcomputer to analyze, without intervention of a human observer, the picture obtained via videocamera, a digitizer and disk-drive. The program, written in BASIC and listed in Appendix I, generates pictures of the monitored animal in the graphics of the computer. These pictures can be analyzed immediately or stored on disk for further analysis.

Analog-Digital Conversion↗
PubMedDate not supplied

The effects of neurotensin, naloxone and haloperidol on elements of excessive grooming behavior induced by bombesin.

The influence of naloxone, haloperidol and neurotensin was investigated on bombesin-induced excessive grooming in rats. All three drugs reduced the amount of bombesin-induced grooming. Haloperidol induced a general reduction in excessive grooming as induced by bombesin, without changing the composition of grooming behavior, whereas naloxone and neurotensin suppressed bombesin-induced grooming and caused a shift in the distribution of grooming elements. The main suppressive effect of these latter drugs appeared to be on the element scratching. From these data it is suggested that bombesin-induced scratching is mainly displayed by activation of opiate receptor systems, whereas the other elements of bombesin-induced excessive grooming are mainly regulated by dopaminergic systems.

Animals↗