RESUMO
Amygdaloid dopamine D(2) receptors play an important role in the modulation of fear/anxiety. Their topographical distribution within the amygdala is however unclear, and their role in unconditioned fear/anxiety remains largely unknown. The aim of this paper was to study the intra-amygdaloid distribution of D(2) receptors and to ascertain their role in unconditioned anxiety. Chemical anatomical studies in the rat, using D(2) and D(3)in situ hybridization, quantitative receptor autoradiography with either [(3)H]raclopride or [(125)I]sulpiride, and D(2)-like immunocytochemistry showed that the highest density of dopamine D(2) receptors is present in the central amygdaloid nucleus, particularly within its latero-capsular division, in which a D(2) but not a D(3) mRNA signal was observed. However, although at considerably reduced densities dopamine D(2) receptors were also found in other locations within the amygdala, including the basolateral nucleus. Behaviorally, the infusion of raclopride (0.75-4 µg/side) in the area of the central amygdaloid nucleus resulted at low doses in the appearance of anxiogenic-like effects in the Shock-Probe Burying test, whereas no effects of raclopride treatment were found at any dose in the Elevated Plus-Maze and the Open-Field test. Our results indicate that amygdaloid dopamine D(2)-like receptors have a topographically differentiated distribution within the rat amygdala, the major location being in the central amygdaloid nucleus. D(2)-like receptors play a role in the modulation of anxiety responses involving a potential differential function of D(2)-like receptors in the central amygdaloid nucleus versus the basolateral amygdaloid nucleus.
Assuntos
Tonsila do Cerebelo/metabolismo , Ansiedade/patologia , Condicionamento Psicológico/fisiologia , Medo , Regulação da Expressão Gênica/fisiologia , Receptores de Dopamina D2/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Análise de Variância , Animais , Ansiedade/metabolismo , Autorradiografia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Eletrochoque/efeitos adversos , Comportamento Exploratório/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , RNA Mensageiro/metabolismo , Racloprida/farmacologia , Ratos , Ratos Wistar , Receptores de Dopamina D2/genética , Receptores de Dopamina D3/genética , Receptores de Dopamina D3/metabolismoRESUMO
Several aldehyde dehydrogenase (ALDH) complexes have been purified from the membranes of acetic acid bacteria. The enzyme structures and the chemical nature of the prosthetic groups associated with these enzymes remain a matter of debate. We report here on the molecular and catalytic properties of the membrane-bound ALDH complex of the diazotrophic bacterium Gluconacetobacter diazotrophicus. The purified ALDH complex is a heterodimer comprising two subunits of 79.7 and 50 kDa, respectively. Reversed-phase high-pressure liquid chromatography (HPLC) and electron paramagnetic resonance spectroscopy led us to demonstrate, for the first time, the unequivocal presence of a pyrroloquinoline quinone prosthetic group associated with an ALDH complex from acetic acid bacteria. In addition, heme b was detected by UV-visible light (UV-Vis) spectroscopy and confirmed by reversed-phase HPLC. The smaller subunit bears three cytochromes c. Aliphatic aldehydes, but not formaldehyde, were suitable substrates. Using ferricyanide as an electron acceptor, the enzyme showed an optimum pH of 3.5 that shifted to pH 7.0 when phenazine methosulfate plus 2,6-dichlorophenolindophenol were the electron acceptors. Acetaldehyde did not reduce measurable levels of the cytochrome b and c centers; however, the dithionite-reduced hemes were conveniently oxidized by ubiquinone-1; this finding suggests that cytochrome b and the cytochromes c constitute an intramolecular redox sequence that delivers electrons to the membrane ubiquinone.
Assuntos
Aldeído Desidrogenase/metabolismo , Citocromos b/metabolismo , Citocromos c/metabolismo , Gluconacetobacter/enzimologia , Cofator PQQ/química , Aldeído Desidrogenase/química , Aldeído Desidrogenase/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Membrana Celular , Citocromos b/química , Citocromos c/química , Regulação Bacteriana da Expressão Gênica/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , NADH NADPH Oxirredutases/metabolismo , OxirreduçãoRESUMO
It is well known that self-mutilating behavior (SMB) is developed in rats and humans during the daily treatment with d-amphetamine. Accordingly, in this work it was found that the daily treatment with 7.5 mg/kg d-amphetamine induced in rats a progressive appearance of SMB. Lower doses (5.0 mg/kg) were uneffective and higher doses (10 mg/kg) produced a pattern of SMB in which the mutilation induced at the beginning of the d-amphetamine administration disappears completely as the treatment progresses. Interestingly, it was also found that REM sleep deprivation (48 h) potentiated significantly the SMB induced by the daily administration of 7.5 mg/kg d-amphetamine, and to lesser extent, the SMB induced by the daily treatment with 10 mg/kg d-amphetamine. R(+)-SCH-23390 a D1 dopamine (DA) receptor antagonist blocked completely or abolished the SMB induced by 7.5 mg/kg d-amphetamine in REM sleep deprived rats while (+/-)-sulpiride a D2 DA receptor antagonist had only a partial blocking effect. Haloperidol a D1/D2 DA receptor antagonist behaved as a D1 antagonist. Our results indicate that REM sleep deprivation enhances the SMB induced by the daily administration of d-amphetamine and suggest the involvement of D1 DA receptors in the mechanism underlying the SMB. A role of REM sleep deprivation is also suggested in the appearance of self-mutilating episodes in d-amphetamine addicts.
Assuntos
Comportamento Autodestrutivo/induzido quimicamente , Comportamento Autodestrutivo/fisiopatologia , Privação do Sono/fisiologia , Sono REM/fisiologia , Animais , Benzazepinas/farmacologia , Estimulantes do Sistema Nervoso Central , Dextroanfetamina , Dopamina/fisiologia , Antagonistas de Dopamina/farmacologia , Haloperidol/farmacologia , Masculino , Ratos , Ratos Wistar , Receptores Dopaminérgicos/fisiologia , Comportamento Autodestrutivo/tratamento farmacológico , Sulpirida/farmacologiaRESUMO
[3H] gamma-Aminobutyric acid (GABA) release was studied in rat brain slices in the absence or presence of cholecystokinin-8 (CCK-8). [3H]GABA release under the conditions used was Ca(2+)-dependent and insensitive to the presence of the glial uptake blocker beta-alanine. While the basal release of [3H]GABA was not affected by CCK-8, the K(+)-stimulated release of [3H]GABA was significantly enhanced by 300 nM of CCK-8 in the caudate putamen, the substantia nigra, the hippocampal formation and the parietofrontal cortex. In the cerebral cortex the CCK-8 enhancement of [3H]GABA release was concentration-dependent and abolished by the CCKB receptor antagonists PD135,158 (1.0 nM) and L-365,260 (100 nM). A significant counteraction of the CCK-8 action was also found with the CCKA receptor antagonist L-364,718 (100 nM) but only in concentrations at which both CCKA and CCKB receptors are blocked. No CCK-8 effects on [3H]GABA release were observed when tetrodotoxin was superfused 5 min before the K(+)-induced [3H]GABA release. It is suggested that the enhancing actions of CCK-8 on K(+)-stimulated [3H]GABA release is mainly related to an activation of CCKB receptors.