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1.
Science ; 275(5296): 83-6, 1997 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-8974398

RESUMO

Regional brain activation was assessed by mapping of Fos-related protein expression in rats trained to self-administration of intravenous nicotine and cocaine. Both drugs produced specific overlapping patterns of activation in the shell and the core of the nucleus accumbens, medial prefrontal cortex, and medial caudate areas, but not in the amygdala. Thus, the reinforcing properties of cocaine and nicotine map on selected structures of the terminal fields of the mesocorticolimbic dopamine system, supporting the idea that common substrates for these addictive drugs exist.


Assuntos
Encéfalo/efeitos dos fármacos , Cocaína/farmacologia , Nicotina/farmacologia , Transtornos Relacionados ao Uso de Opioides/etiologia , Transtornos Relacionados ao Uso de Substâncias/etiologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Encéfalo/metabolismo , Mapeamento Encefálico , Cocaína/administração & dosagem , DNA/metabolismo , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nicotina/administração & dosagem , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Proteínas Proto-Oncogênicas c-fos/biossíntese , Ratos , Reforço Psicológico , Autoadministração , Fator de Transcrição AP-1/metabolismo
2.
Eur J Neurosci ; 8(11): 2247-56, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8950089

RESUMO

Rats were trained for nicotine intravenous infusions in a self-administration paradigm. The effect of nicotine self-administration on regional brain activity was studied by mapping changes of c-fos expression. Specific nicotine effects were determine by comparing the patterning of Fos-like immunoreactivity (Fos-Ll) in nicotine self-administering rats with that in three different control groups. Controls included rats exposed to the same manipulation as nicotine self-administering rats who received intravenous saline instead of nicotine. In addition, two groups of untrained sham-operated rats exposed daily to the same operant boxes were included: one group had the same food restriction used in the operant training, the other was fed ad libitum. Nicotine self-administration, exposure to saline and food restriction increased Fos-Ll in 43, 33 and three brain regions, respectively, when compared with the control group fed ad libitum. Computer-assisted image analysis of Fos-Ll profiles performed on 16 relevant limbic and sensory structures showed that in saline-treated rats a significant (P < 0.01) increase of Fos-Ll profiles was observed in medial prefrontal cortex, lateral septum, core and ventral shell of nucleus accumbens, claustrum, amygdaloid nuclei, paraventricular thalamic nucleus and lateral geniculate nucleus. A significant (P < 0.01) further increase produced by nicotine was found in medial prefrontal cortex and ventral shell of nucleus accumbens. Interestingly, cingulate and piriform cortex, superior colliculus and medial terminal nucleus of the accessory optic tract were specifically activated by nicotine but not saline. These results show that nicotine self-administration activates sensory structures, as well as limbic structures involved in natural rewarding pathways. The results suggest the involvement of restricted terminal regions of the mesocorticolimbic dopaminergic system in the maintenance of nicotine self-administration.


Assuntos
Encéfalo/fisiologia , Genes fos , Nicotina/farmacologia , Proteínas Proto-Oncogênicas c-fos/biossíntese , Reforço Psicológico , Autoadministração , Análise de Variância , Animais , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Condicionamento Operante/efeitos dos fármacos , Expressão Gênica , Genes fos/efeitos dos fármacos , Imuno-Histoquímica , Infusões Intravenosas , Masculino , Nicotina/administração & dosagem , Especificidade de Órgãos , Ratos , Ratos Wistar
3.
Neuroscience ; 61(3): 429-33, 1994 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7969919

RESUMO

Age-related decline of cognition and memory, in humans and other animals, appears to be associated with neuronal loss. Experimental and clinical evidence has shown that the hippocampal formation is one of the brain regions most vulnerable to the ageing process. Because excess of glutamate is neurotoxic to hippocampal neurons, abnormalities in glutamate neurotransmitter function may play a crucial role in neurodegenerative disorders, especially in conjunction with brain ageing. We have used in situ hybridization to study the expression of the two major alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor subunits, involved in the control of calcium permeability in the young adult and aged rat hippocampus. We show that the levels of messenger RNA encoding the AMPA-selective glutamate receptor subunit-1 (GluR1 or GluRA) and AMPA-selective glutamate receptor subunit-2 (GluR2 or GluRB) are highest in the dentate gyrus, followed by the CA1 and CA3 hippocampal subfields. We also show that the levels of both messenger RNAs decrease differentially with age in all subfields of the hippocampus. Finally, the GluR1/GluR2 messenger RNA ratios increase in the aged hippocampus, particularly in the CA3 subfield, suggesting that altered calcium homeostasis may contribute to age-related neuronal death.


Assuntos
Envelhecimento/metabolismo , Cálcio/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Receptores de AMPA/biossíntese , Animais , Autorradiografia , Morte Celular/fisiologia , Hipocampo/citologia , Hipocampo/crescimento & desenvolvimento , Hibridização In Situ , Masculino , Sondas de Oligonucleotídeos , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar
4.
EMBO J ; 9(8): 2459-64, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2369898

RESUMO

Brain-derived neurotrophic factor (BDNF) is a protein that allows the survival of specific neuronal populations. This study reports on the distribution of the BDNF mRNA in the adult mouse brain, where the BDNF gene is strongly expressed, using quantitative Northern blot analysis and in situ hybridization. All brain regions examined were found to contain substantial amounts of BDNF mRNA, the highest levels being found in the hippocampus followed by the cerebral cortex. In the hippocampus, which is also the site of highest nerve growth factor (NGF) gene expression in the central nervous system (CNS), there is approximately 50-fold more BDNF mRNA than NGF mRNA. In other brain regions, such as the granule cell layer of the cerebellum, the differences between the levels of BDNF and NGF mRNAs are even more pronounced. The BDNF mRNA was localized by in situ hybridization in hippocampal neurons (pyramidal and granule cells). These data suggest that BDNF may play an important role in the CNS for a wide variety of adult neurons.


Assuntos
Encéfalo/metabolismo , Fatores de Crescimento Neural/genética , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/análise , Sequência de Aminoácidos , Animais , Autorradiografia , Sequência de Bases , Fator Neurotrófico Derivado do Encéfalo , Clonagem Molecular , DNA/genética , Biblioteca Gênica , Camundongos , Dados de Sequência Molecular , Especificidade de Órgãos , Radioisótopos de Fósforo , RNA Mensageiro/genética
5.
Eur J Neurosci ; 2(5): 471-480, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-12106033

RESUMO

Adhesion molecule on glia (AMOG) is a 45 - 50 kD cell surface glycoprotein structurally similar to the Na, K-ATPase beta-subunit and associated with the catalytic subunit of this enzyme. Previous immunofluorescence results had suggested that AMOG is transiently expressed on Bergmann glia during mouse cerebellar development, and antibody-inhibition results have implicated it in the migration of granule neurons. We report that, while AMOG mRNA is detected in Bergmann glia during the migratory period, this astrocyte derivative continues to express AMOG mRNA at similar levels in adult mice suggesting a functional role for AMOG in adulthood. Evidence from RNA and protein blot analyses that AMOG is present before birth, increasing about ten fold in adult mouse brain and cerebellum is also provided. RNA blot analysis of astrocyte-enriched cell populations and in situ hybridization results show that astrocytes synthesize AMOG mRNA in all regions of the developing and adult brain. In the adult, AMOG mRNA is more abundant in grey than white matter and, among grey matter regions, highest in cerebellar cortex. These results indicate a relationship between density of neuronal elements and AMOG expression. It is further speculated that AMOG is part of a Na,K-ATPase complex expressed preferentially by astrocytes in mouse brain.

6.
Psychopharmacology (Berl) ; 86(1-2): 118-24, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-2410943

RESUMO

The time course of different pharmacological effects of L-5-hydroxytryptophan (5-HTP) during continued treatment was studied in rats. 5-HTP was administered three times daily at 100 mg/kg IP in combination with the peripheral decarboxylase inhibitor carbidopa (10 mg/kg) for 14 days. 5-HTP induced a pronounced increase of the threshold for maximal electroconvulsions, decreased body temperature and body weight and induced characteristic "wet-dog" shake behaviour. Whereas the anticonvulsant effect increased during the 14 days of treatment, tolerance developed to the excitatory and, less rapidly, to the hypothermic and anorexigenic effects of 5-HTP. Biochemical determinations showed marked increases in 5-HTP and its metabolites, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in both plasma and brain throughout the period of treatment. The mechanisms underlying the different time-courses of the functional effects of 5-HTP during continued treatment are not clear, but effects on catecholaminergic systems as well as regional differences in 5-HT increases in the brain might be involved.


Assuntos
5-Hidroxitriptofano/farmacologia , Transtornos dos Movimentos/induzido quimicamente , Convulsões/induzido quimicamente , 5-Hidroxitriptofano/análise , Animais , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Carbidopa/farmacologia , Interações Medicamentosas , Tolerância a Medicamentos , Feminino , Ácido Hidroxi-Indolacético/análise , Ratos , Ratos Endogâmicos , Serotonina/análise
7.
Neuropharmacology ; 23(9): 1041-8, 1984 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6083501

RESUMO

The effect of L-5-hydroxytryptophan (5-HTP) on the threshold for maximal electroconvulsions was compared with concomitant changes in levels of 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in plasma and brain of rats. A single injection of 5-HTP (100 mg/kg, i.p.) caused significant elevation in seizure threshold which was markedly intensified by pretreatment with the decarboxylase inhibitor carbidopa (10 mg/kg, i.p., 0.5 hr previously). Pretreatment with carbidopa also resulted in behavioural changes, i.e. the characteristic "wet-dog shake" behaviour became much more prominent. Biochemically, administration of 5-HTP gave rise to significant elevation of levels of 5-HTP, 5-HT and 5-HIAA in plasma and brain. Carbidopa increased levels of 5-HTP in the brain, decreased 5-HIAA in the periphery but did not alter the elimination rate of 5-HTP in plasma. In both naive rats and rats pretreated with carbidopa, a significant correlation was found between levels of 5-HTP and 5-HIAA in plasma and brain following injection of 5-HTP. Furthermore, in the absence of carbidopa, the increases of levels of 5-HT in plasma and brain induced by 5-HTP were correlated in a significant fashion. When the changes in the electroconvulsive threshold were compared with respective changes in levels of 5-hydroxyindoles, a significant correlation was obtained between threshold elevations and increases of 5-HTP and 5-HT in the brain. In rats treated with 5-HTP, without decarboxylase inhibitor, a significant correlation was found between increases in 5-HT in plasma and the seizure threshold. The results suggest that analysis of 5-hydroxyindoles in plasma may represent a useful tool for the estimation of 5-HT metabolism in brain.


Assuntos
5-Hidroxitriptofano/farmacologia , Anticonvulsivantes , Química Encefálica/efeitos dos fármacos , Ácido Hidroxi-Indolacético/metabolismo , Serotonina/metabolismo , 5-Hidroxitriptofano/metabolismo , Animais , Carbidopa/farmacologia , Eletrochoque , Feminino , Ácido Hidroxi-Indolacético/sangue , Ratos , Ratos Endogâmicos , Serotonina/sangue , Fatores de Tempo
8.
Naunyn Schmiedebergs Arch Pharmacol ; 322(3): 210-5, 1983 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6306485

RESUMO

The effect of aminooxyacetic acid (AOAA, 90 mg/kg i.v.) on bicuculline, picrotoxin and 3-mercaptopropionic acid (3-MPA) induced convulsions and on GABA concentrations in cerebellum, whole brain and a synaptosomal fraction of whole brain was investigated. At various intervals after AOAA the rats were either injected with one of the convulsive drugs or sacrificed for analysis of the GABA concentration. AOAA caused a rapid initial (0-30 min) and a later slower increase of GABA in cerebellum and whole brain. In the synaptosomal fraction the GABA accumulation was delayed and less pronounced when compared to the whole brain. The bicuculline induced convulsions were markedly potentiated during the first hour but completely blocked from 2-6 h after AOAA. Picrotoxin showed a somewhat different pattern to bicuculline in the interactions with AOAA. The initial strong potentiation was not observed but the later phase of protection was present. In the interactions with 3-MPA, the effect of AOAA was always protective. The time to onset of convulsions was gradually increased during the first 30 min after AOAA. This protective effect remained practically unchanged up to 6 h after AOAA. However, once started, the convulsions were generally of the same duration and intensity. The results can be interpreted as GABA accumulating after AOAA stimulates GABA receptors to a degree more or less proportional to the whole brain GABA concentration and further that GABA synthetized in neurons is liberated, stimulates inhibitory bicuculline sensitive (predominant) and excitatory bicuculline insensitive receptors and is captured to a large extent by non-neuronal cells.


Assuntos
Acetatos/farmacologia , Ácido Amino-Oxiacético/farmacologia , Encéfalo/metabolismo , Receptores de Superfície Celular/metabolismo , Ácido gama-Aminobutírico/metabolismo , Ácido 3-Mercaptopropiônico/toxicidade , Animais , Bicuculina/toxicidade , Compartimento Celular , Fracionamento Celular , Cerebelo/metabolismo , Interações Medicamentosas , Feminino , Picrotoxina/toxicidade , Ratos , Receptores de GABA-A , Convulsões/induzido quimicamente , Sinaptossomos/metabolismo
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