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Biomedical subjects

A H Mohammed

Publications and source records attributed to A H Mohammed.

At least 19 recordsLinked to original sources
PubMed2006

Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced hyperactivity, acetylcholine release and dopamine metabolism in the nucleus accumbens.

The aim of the present study was to investigate the effects of stimulation of D2 receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the effects of prefrontal D2 stimulation under PCP treatment on dialysate concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus accumbens were also investigated. Sprague-Dawley male rats were implanted with guide cannulae to perform bilateral injections into the medial PFC of the D2 agonist quinpirole (1.5 and 5 microg/side). Horizontal and vertical spontaneous motor activity and the motor activity induced by systemic injections of the PCP (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole (1.5 and 5 microg/side) significantly decreased horizontal and vertical spontaneous motor activity in a dose-related manner. These effects were blocked by the D2 antagonist raclopride (5 microg/side). Microinjections of quinpirole (1.5 and 5 microg/side) into the PFC also significantly attenuated the hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate concentrations of acetylcholine, and dopamine metabolites in the nucleus accumbens. These increases were also reduced by injections of quinpirole (5 microg/side) into the PFC. These results suggest that the stimulation of prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and PCP-induced motor activity and also in the neurochemical changes produced by PCP in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Levels of neurotrophic factors in the hippocampus and amygdala correlate with anxiety- and fear-related behaviour in C57BL6 mice.

The present study tested whether individual differences in anxiety- and fear-related behaviour are associated with between-subjects variation in postmortem brain levels of selected neurotrophic factors. Naïve C57BL6/J mice of both sexes were subjected either to an elevated plus maze test or to a Pavlovian fear conditioning paradigm. Two days after behavioural assays, the mice were sacrificed for postmortem quantification of the protein levels of brain derived neurotrophic factors (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the hippocampus and amygdala. Significant correlations between behavioural measures and postmortem regional neurotrophic factor contents were revealed. The magnitude of anxiety-like behaviour in the elevated plus maze was positively related to dorsal hippocampal BDNF levels, but negatively related to NGF levels in dorsal hippocampus and in the amygdala. On the other hand, the expression of conditioned fear is positively related to amygdala BDNF and NGF levels, and to dorsal hippocampal NGF levels. Our results add to existing reports in human as well as in animals of correlation between anxiety trait and gross measures of hippocampal volume or activation levels. Moreover, a distinction between spontaneous and learned (or conditioned) anxiety/fear would be relevant to the identification of neurotrophin signalling mechanisms in the hippocampus and amygdala implicated in anxiety and related psychopathology.

Amygdala↗
PubMed2000

Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain.

A number of studies have demonstrated that both morphological and biochemical indices in the brain undergo alterations in response to environmental influences. In previous work we have shown that rats raised in an enriched environmental condition (EC) perform better on a spatial memory task than rats raised in isolated conditions (IC). We have also found that EC rats have a higher density of immunoreactivity than IC rats for both low and high affinity nerve growth factor (NGF) receptors in the basal forebrain. In order to determine if these alterations were coupled with altered levels of neurotrophins in other brain regions as well, we measured neurotrophin levels in rats that were raised in EC or IC conditions. Rats were placed in the different environments at 2 months of age and 12 months later brain regions were dissected and analyzed for NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) levels using Promega ELISA kits. We found that NGF and BDNF levels were increased in the cerebral cortex, hippocampal formation, basal forebrain, and hindbrain in EC animals compared to age-matched IC animals. NT-3 was found to be increased in the basal forebrain and cerebral cortex of EC animals as well. These findings demonstrate significant alterations in NGF, BDNF, and NT-3 protein levels in several brain regions as a result of an enriched versus an isolated environment and thus provide a possible biochemical basis for behavioral and morphological alterations that have been found to occur with a shifting environmental stimulus.

Animals↗
PubMed2000

Genetic dissection of nicotine-related behaviour: a review of animal studies.

Nicotine has a broad spectrum of behavioural effects. A considerable body of data has emerged indicating genetic factors regulate the behavioural effects of nicotine. Experimental genetic techniques have been invaluable in generating knowledge on the interrelationship of genetic factors and behavioural responsiveness to nicotine. Three different approaches have been invoked to explore the relationship of genetic factors to response to nicotine. Firstly, the classical genetic tool of inbred lines has been exploited to delineate genetic influences in the effects of nicotine. Secondly, the use of selectively bred lines has been profitably employed to reveal genetic differences in behavioural responses, such as cognition and exploration, to nicotine. These approaches have also provided useful information on the contribution of genetic factors influencing nicotinic receptors function. Finally the molecular genetic technique of gene targetting to create mice with null mutations of specific genes in the central nervous system, which is having a tremendous impact in drug addiction research, has also been employed to gain insight into the molecular and cellular basis of nicotine action. These techniques are proving to be invaluable in dissecting the role of different subunits of the nicotinic acetylcholine receptors on behaviour. This paper provides a survey of the animal studies that have used the above mentioned techniques to gain insight into genetic basis of the behavioural effects of nicotine.

Animals↗
PubMed2000

Antinociceptive activity of Euphorbia heterophylla roots.

Following an identified use of the plant as analgesic in traditional medicine, the hexane, chloroform and ethyl acetate extracts of Euphorbia heterophylla root have been tested for antinociceptive activity in rats. All extracts showed significant effects at doses of 150-300 mg/kg i.p.

Analgesics↗
PubMed1999

Effects of environmental enrichment on cognitive function and hippocampal NGF in the non-handled rats.

In this study we examine whether exposure to differential housing after weaning would counteract the effects of postnatal handling (H) or nonhandling (NH) treatment by affecting learning and memory processes in young rats. In addition, we seek to determine if experience in enriched environment would alter hippocampal nerve growth factor (NGF) levels which is one of the factors known to be involved in the regulation of the survival and differentiation of developing basal forebrain neurones. Rats were either exposed to handling treatment, or left undisturbed starting day 1 after birth through day 21. After weaning on day 22, we exposed half of the H rats and half of the NH rats to environmental enrichment for 60 days. The other respective half of the rats was housed in isolated environmental condition (IC). Behavioural measures were taken in open field test, and spatial water maze test. Exposure to enriched environment following postnatal handling and nonhandling increased hippocampal NGF levels, and improved cognitive function in the both groups, with NH rats being more responsive to the effects of enrichment. Our results suggest that environmental enrichment has the potential to prevent or reduce the cognitive and neurochemical deficits in the adult animals associated with nonhandling.

Animals↗
PubMed1999

Changes in brain nerve growth factor levels and nerve growth factor receptors in rats exposed to environmental enrichment for one year.

This study examined the effects of long-term differential rearing on levels of brain nerve growth factor, its receptors, and their relationships to cognitive function. Adult rats (two months old) were placed into either enriched or standard housing conditions where they remained for 12 months. Animals from the enriched condition group had significantly higher levels of nerve growth factor in hippocampus, visual and entorhinal cortices compared with animals housed in isolated condition. Immunohistochemical analysis of brain tissue from the medial septal area revealed higher staining intensity and fibre density with both the low-affinity and the high-affinity nerve growth factor receptors. Enriched rats performed better than isolated rats in acquisition of spatial learning and had lower locomotion scores in the open field. These results provide further evidence that experimental stimulation results in increased production of trophic factors and structural reorganization in specific brain regions known to be involved in cognitive function.

Age Factors↗
PubMed1999

Neonatal handling in rats induces long-term effects on dynorphin peptides.

The effects of neonatal handling on the opioid dynorphin peptides in the brain and pituitary gland of Sprague-Dawley rats were investigated. Ten weeks after the neonatal handling, handled rats had higher tissue levels of dynorphin A and B in the hypothalamus, pituitary gland and striatum and slightly higher dynorphin B levels in the hippocampus, medulla oblongata and midbrain as compared with non-handled controls. The results indicate a persistent upregulation of the dynorphin system in certain brain areas after neonatal handling, which could contribute to the behavioural changes in these rats observed later in life. Observation in the open field and the elevated plus-maze tests confirmed behavioural effects of neonatal handling, i.e. showing that handled rats exhibit attenuated fearfulness in novel environments as compared with non-handled rats.

Animals↗
PubMed1998

Environmental enrichment results in higher levels of nerve growth factor mRNA in the rat visual cortex and hippocampus.

Evidence for structural modifications in the brain following environmental changes have been provided during the last decades. The most pronounced alterations following environmental manipulations have been found in the visual cortex. These plastic changes are supposed to reflect reorganization of neuronal connections involved in postnatal development and adult adjustments of connections involved in sensori-perceptual processing and learning. Potential candidates to mediate these changes are neurotrophins. Nerve growth factor (NGF) has been associated with cognitive functions and shown to improve the performance of aged rats in spatial learning and memory task. In the central nervous system, NGF is of importance for development and maintenance of cholinergic neurons and atrophy of cholinergic neurons is strongly correlated with learning and memory impairments. Exposure to enriched environmental conditions improves learning and problem-solving ability and results in plastic changes in the brain. This study examined the effect of environmental enrichment on expression of NGF mRNA in the rat visual cortex and hippocampus. Rats housed in groups in a stimulus-rich environment for 30 days had significantly higher levels of NGF mRNA than rats housed individually in single cages without stimulus-enrichment. We have recently presented results showing higher levels of neurotrophin-3 (NT-3) mRNA and improved spatial learning following environmental enrichment, and suggest that an interplay involving the neurotrophins NGF and NT-3 may be mediating experience-induced structural changes.

Animals↗
PubMed1998

Environmental enrichment selectively increases 5-HT1A receptor mRNA expression and binding in the rat hippocampus.

Environmental enrichment augments neuronal plasticity and cognitive function and possible mediators of these changes are of considerable interest. In this study, male rats were exposed to environmental enrichment or single housing for 30 days. Rats from the enriched group had significantly higher 5-HT1A receptor mRNA expression in the dorsal hippocampus (62%, 59% and 44% increase in the CA1, CA2 and CA3 subfields, respectively). This was associated with significantly higher [3H]8-OH-DPAT binding in the inferior part of CA1. No changes were seen for 5-HT2A or 5-HT2C receptor mRNAs. The neuronal plasticity detected after environmental change may be mediated, in part, through 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Reciprocal changes in expression of mRNA for nerve growth factor and its receptors TrkA and LNGFR in brain of aged rats in relation to maze learning deficits.

Quantitative in situ hybridization was used to examine the expression of mRNA for nerve growth factor (NGF) and its receptors, p140Trk (TrkA) and p75LNGFR (LNGFR), in different brain regions of adult (3-month-old) and aged (27-month-old) Wistar rats. The brain regions studied were hippocampus (dentate gyrus, CA3 region), basal forebrain (medial septum, diagonal band) and caudate-putamen. Prior to hybridization histochemistry behaviorally impaired as well as severely impaired animals were selected from a large group of old rats according to their performance in the Morris water maze. The impaired rats showed longer escape latencies and, thus, implicitly impaired performance in the place version of the task, but did not differ from adult controls on the platform crossing measure registered during the spatial probe trial. The severely impaired rats were significantly impaired on both measures, both in comparison with the adult animals and in comparison with the impaired aged rats. Inspection of the hippocampus revealed no age- or performance-related changes in NGF mRNA levels. The overall expression of TrkA mRNA in basal forebrain and caudate was found to be decreased in the impaired (-20%) as well as the severely impaired aged rats (-17%). A significant increase in p75LNGFR mRNA was found in the basal forebrain of the impaired rats in comparison with the severely impaired aged rats (+35%) and adult animals (+33%). These findings show that age-related maze performance deficits are accompanied by a decrease in basal forebrain and striatal TrkA mRNA expression. The increase in basal forebrain LNGFR mRNA levels observed in impaired, but not severely impaired, aged rats may reflect an early manifestation of processes underlying age-related cognitive deficits and may constitute a restorative and/or compensatory mechanism, since these rats displayed fewer deficits in navigation of the maze.

Aging↗
PubMed1997

Effects of neonatal stimulation on later cognitive function and hippocampal nerve growth factor.

This study examined the behavioural and physiological effects of chronic mild stress on neonatally handled and non-handled rats. Neonatally handled and non-handled rats were exposed to chronic mild stress from weaning time to 6 months of age. They were behaviourally tested at 6 months of age, and sacrificed for analysis of nerve growth factor (NGF) in the hippocampus and hypothalamus. In contrast to the reported deleterious effect of acute strong stress, mild stress appeared to stimulate production of NGF in the hippocampus and improve spatial learning in both handled and nonhandled rats. Because neonatal handling produces neuroanatomical changes in the rat hippocampus and enhances cognitive function throughout the rats life span, these results implicate hippocampal NGF in the neuroprotective effects of handling.

Aging↗
PubMed1996

Expression of neurotrophin-3 mRNA in the rat visual cortex and hippocampus is influenced by environmental conditions.

Environmental enrichment results in structural changes in the brain. Recent findings indicate involvement of neurotrophins in neuronal plasticity. This study examined the effect of environmental complexity on the levels of neurotrophin-3 (NT-3) mRNA in the rat visual cortex and hippocampus, studied by in situ hybridization. Rats housed in groups in a complex, stimulating environment had significantly higher levels of NT-3 mRNA in the visual cortex and the hippocampus than rats housed in individual cages without stimulating objects. These results indicate a possible role for NT-3 in synaptic plasticity.

Animals↗
PubMed1995

Sleep fragmentation, and changes in locomotor activity and body temperature in trypanosome-infected rats.

The rest-activity and body temperature 24 h cycles, as well as the structure of spontaneous sleep, were studied in rats 3 weeks after infection with monomorphic Trypanosoma brucei brucei. This parasite belongs to the species of trypanosomes that causes in humans African sleeping sickness, a neuropsychiatric syndrome that involves alterations of endogenous biological rhythms. In the infected rats, entrained to a 12 h:12 h photoperiod, a considerable hypokinesia was detected during the hours of darkness. A significant oscillation of the body temperature during 24 h was lost in some infected animals. In the other infected animals, the body temperature cycle displayed a lower amplitude and a phase advance. The mean temperature was slightly higher in the infected than in control rats during the period of light. A detailed analysis of the structure of spontaneous sleep, based on daytime electroencephalographic recordings, revealed during trypanosome infection an increased relative proportion of wake, and a decreased percent value of synchronized sleep. A marked reduction of the mean REM latency and a fragmented pattern of synchronized sleep, resulting in a considerable alteration of the REM-non-REM sleep sequences, were also observed in the infected animals. These findings indicate that trypanosomiasis in the rat results in a striking sleep fragmentation, as well as in changes of locomotor activity and body temperature rhythm. Thus, trypanosome infection in the rat provides an experimental model of sleep dysregulation in a structurally intact brain, and may provide an animal model of endogenous rhythm changes documented in African sleeping sickness.

Analysis of Variance↗
PubMed1994

Interferon-gamma and a factor derived from trypanosomes cause behavioural changes in the rat.

A newly isolated interferon-gamma (IFN-gamma) immunoreactive molecule, "neuronal IFN-gamma", and recombinant lymphocyte-derived IFN-gamma were injected intracerebroventricularly (i.c.v.) through a previously implanted cannula into adult male rats during both the light and the dark phases of the light/dark cycle. The two molecules caused a reduction in both frequency and duration of rearing and locomotion during the dark, but not the light, phase. A molecule isolated from Trypanosoma brucei brucei, a parasite of the same subspecies of trypanosomes which causes African sleeping sickness, can induce production and release of IFN-gamma and "neuronal IFN-gamma" from lymphocytes and neurons, respectively. I.c.v. injection of this factor also reduced rearing during the dark period, but to a less extent. Thus, "neuronal IFN-gamma" appears to have effects on animal behaviour in common with lymphocyte-derived IFN-gamma. This study highlights the potential role of these cytokines in behaviour disturbances.

Animals↗
PubMed1994

A novel anticholinesterase THB013: biochemical and behavioural studies.

Clinical trials with tacrine (THA) have resulted in elevations of liver enzymes in Alzheimer patients that showed improvement. In an effort to minimize these side effects several THA analogues were synthesized. These analogues were compared to THA in biochemical as well as behavioural studies. In this study, the biochemical effects of THA and one of these analogs, THB 013, on plasma cholinesterase activity, cholinergic receptors as well as the effect of these drugs on spatial learning in adult rats were examined. THB 013 was, at lower concentration, more efficacious in inhibiting plasma cholinesterase as well as blocking the scopolamine induced disruption of spatial learning when administered 10 min before the scopolamine injection. It is possible that THB 013 with more potent cholinergic effects than THA might be useful in the treatment of Alzheimer's disease.

Alzheimer Disease↗