ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Nicotine has been shown to have effects on anxiety and depression in both human and animal studies. These studies suggest that nicotinic acetylcholine receptors (nAChRs) can modulate the function of pathways involved in stress response, anxiety and depression in the normal brain, and that smoking can result in alterations of anxiety level and mood. The effects of nicotine are complex however, and nicotine treatment can be either anxiolytic or anxiogenic depending on the anxiety model tested, the route of nicotine administration and the time course of administration. The paradoxical effects of nicotine on emotionality are likely due to the broad expression of nAChRs throughout the brain, the large number of nAChR subtypes that have been identified and the ability of nicotine treatment to both activate and desensitize nAChRs. Activation of nAChRs has been shown to modulate many systems associated with stress response including stress hormone pathways, monoaminergic transmission and release of classical neurotransmitters throughout the brain. Local administration studies in animals have identified brain areas that may be involved in the anxiogenic and anxiolytic actions of nicotine including the lateral septum, the dorsal raphe nuclei, the mesolimbic dopamine system and the hippocampus. The ensemble of studies to date suggest that under certain conditions nicotine can act as an anxiolytic and an antidepressant, but that following chronic use, adaptations to nicotine can occur resulting in increased anxiety and depression following withdrawal.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

In the present study we tested the hypothesis that baclofen, a GABA-B receptor agonist, attenuates methamphetamine self-administration. Fifteen rats were trained to self-administer i.v. injections of methamphetamine (0, 0.0625, 0.125 and 0.25 mg/kg/injection) on a progressive ratio schedule of reinforcement, and then were tested under the influence of two doses of baclofen (2.5 or 5.0 mg/kg, i.p.). Baclofen significantly reduced break points at all doses of methamphetamine, producing a dose-orderly shift of the methamphetamine dose–response function to the right. These data suggest that pretreatment with baclofen reduces methamphetamine reward. These data are consistent with other studies showing impairment of drug reward after pretreatment with baclofen and add further support to the idea that GABA-B agonists may be useful in the treatment of drug addiction.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Several studies show that although function may recover after brain damage the insult can nevertheless cause accelerated deterioration in old age. This has been interpreted as indicating reduced neuronal capacity to counteract age-related decline with plastic changes. Psychosocial and compensatory factors obscure the neuronal explanation. Since the speed of processing sequential temporal information is impaired in developmental dyslexia, we investigated its dependence on age (20–59 years) in psychosocially comparable groups of dyslexic and fluent readers using six tasks. Processing speed was impaired in dyslexia and decreased with age. The decrement was faster in dyslexic than normal readers in processing periodic stimuli. No exacerbation occurred in reading and other experiential factors. Our results, therefore, support the neuronal explanation.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Individuals with Williams syndrome (WMS) show an interesting dissociation of ability within the visuospatial domain, particularly between face perception and other visuospatial tasks. In this population, using tasks matched for stimuli, required response, and difficulty (for controls) is critical when comparing performance across these areas. We compared WMS individuals with a sample of typically developing 8- and 9-year-old children, and with a sample of adults, closer to the WMS participants in chronological age, in order to investigate performance across two precisely matched perceptual tasks, one assessing face processing and the other assessing proficiency in processing stimuli location. The pattern of performance seen in WMS, but not in controls, implicates a specific deficit of dorsal stream functioning in this syndrome.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We studied the relationship among dopamine receptor D2 (DRD2) Taq I genetic polymorphism, caudate nucleus volumetry as measured using MRI and neuropsychological functions in 49 memory impaired older people. Compared with DRD2 A1 carriers, subjects homozygous for the DRD2 A2 allele performed poorer in a measure of general cognitive functioning (MMSE) and in long term verbal memory, and presented reduced left caudate nucleus volumes. Caudate nucleus atrophy correlated with cognitive measures influenced by the genetic polymorphism and with visual memory performance. Our findings suggest that among the aged with cognitive impairments, the homozygous status for the A2 allele of the DRD2 Taq I polymorphism is associated with diminished cognitive performance and increased atrophy in the striatum.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Our previous studies have suggested a close relationship between vasopressin and endolymphatic hydrops, or the increased volume of endolymph in the inner ear. Endolymphatic hydrops is also thought to occur in Ménière's disease patients. In the kidney collecting duct, vasopressin induces the expression of aquaporin-2 (AQP2), resulting in increased water reabsorption. We explored the possibility, using a quantitative PCR method, that vasopressin regulates the expression of AQP2 mRNA in the rat inner ear, as it does in the kidney. The levels of AQP2 mRNA in the cochlea and endolymphatic sac were significantly higher in rats treated with vasopressin than the levels in control animals. We speculate that over-expression of AQP2 may be involved in the formation of endolymphatic hydrops.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Missense mutations in the human Cu/Zn superoxide dismutase gene (SOD-1) cause many cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS). The accumulation of intracellular calcium is one of the primary mechanisms of motor neuronal degeneration associated with mutations in SOD-1. In order to investigate the effect of various calcium modulators and the SOD-1 mutation on neuronal death, we tested motoneuron-neuroblastoma hybrid (VSC 4.1) cells constitutively expressing human SOD-1 gene with mutations (A4V, G93A) or wild-type. These cells were treated with endogenous calcium releaser (ryanodine, thapsigargin, cyclic ADP-ribose) or calcium mobilizer through cell membrane (4-bromo-calcium ionophore A23187). In particular, calcium ionophore reduced survival in the cells expressing mutant SOD-1. Cell death was associated with increased nitric oxide (NO) generation. This toxicity was attenuated when a nitric oxide synthase (NOS) inhibitor was added. Exogenous NOadministration (S-nitrosoglutathione) also induced cell death. The NO-dependent guanylyl cyclase-cGMP cascade inhibitor protected the mutant cells from the toxic effects of calcium ionophore. Our data suggests that motoneuron degeneration with the SOD-1 mutation may be mediated by calcium dysregulation, particularly by the exogenous calcium influx. This process induces oxidative stress generation that results in motor neuronal death through the guanylyl cyclase-cGMP dependent cascade.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Orphanin FQ/nociceptin, (OFQ/N) the endogenous ligand for the ORL-1 receptor, has been shown previously to modulate extracellular dopamine concentration in the nucleus accumbens following both intracerebroventricular and intra-ventral tegmental area administration. However, it is unclear whether or not this is a result of a direct action of OFQ/N on ORL-1 receptors located on dopamine neurons. We sought evidence for expression of the ORL-1 receptor in dopamine cells located in the ventral tegmental area and substantia nigra of the rat brain using double-labelin situhybridization. Within the ventral tegmental area, 91% of tyrosine hydroxylase-positive cells were also positive for ORL-1 hybridization. Similarly, in the substantia nigra 90% of tyrosine hydroxylase-positive cells in the zona compacta expressed ORL-1 message and 84% of tyrosine hydroxylase-positive cells in the zona reticulata colocalized ORL-1 message. These data provide the anatomical basis for a direct modulatory effect of OFQ/N on mid-brain dopamine neurons.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID