RESUMO
Amphetamine (AMPH) abuse is a world concern and a serious public health problem. Repeated administration of high doses of AMPH induces neuropsychiatric consequences, including addiction, reward and psychosis, whose pharmacological treatment has shown limited effectiveness. The m-trifluoromethyl-diphenyldiselenide [(m-CF3-PhSe)2] has been documented as a promising pharmacological agent in different animal models related to oxidative damage. In this study, we examined the influence of (m-CF3-PhSe)2 on withdrawal following re-exposure to AMPH. Wistar rats received d,l-AMPH or saline in the conditioned place preference (CPP) paradigm for 8days. Then, half of each initial (AMPH or saline) experimental group was treated with (m-CF3-PhSe)2 or vehicle, resulting in four final groups: i) Saline/vehicle; ii) (m-CF3-PhSe)2/saline; iii) AMPH/vehicle; and iv) AMPH/(m-CF3-PhSe)2. After fourteen days of (m-CF3-PhSe)2 treatment, animals were re-exposed to AMPH or vehicle in the CPP paradigm for three more days in order to assess drug re-conditioning and memory/locomotor activity, performed 24h after AMPH re-exposure in the CPP and the Y maze, respectively. Subsequently, ex-vivo assays were carried out in samples of the prefrontal cortex (PFC) of the animals. The (m-CF3-PhSe)2 treatment was able to prevent AMPH-induced re-conditioning symptoms in rats. Behavioral observations in the Y maze task showed no significant changes. AMPH exposure was able to increase 5-HT uptake as well as oxidative damage in the PFC, whereas (m-CF3-PhSe)2 treatment exerted a preventative effect against these alterations. The current findings suggest that (m-CF3-PhSe)2 might be considered a promising therapeutic tool for AMPH-induced addiction.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Anfetamina/farmacologia , Atividade Motora/efeitos dos fármacos , Compostos de Organossilício/farmacologia , Síndrome de Abstinência a Substâncias , Animais , Aprendizagem por Associação/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The hydration of solid dimyristoylphosphatidylethanolamine (DMPE) produces a negligible shift in the asymmetric stretching frequency of the phosphate groups in contrast to dimyristoylphosphatidylcholine (DMPC). This suggests that the hydration of DMPE is not a consequence of the disruption of the solid lattice of the phosphate groups as occurs in DMPC. The strong lateral interactions between NH(3) and PO(2)(-) groups present in the solid PEs remain when the lipids are fully hydrated and seem to be a limiting factor for the hydration of the phosphate group hindering the reorientation of the polar heads. The lower mobility is reflected in a higher energy to translocate the phosphoethanolamine (P-N) dipoles in an electrical field. This energy is decreased in the presence of increasing ratios of PCs of saturated chains in phosphoethanolamine monolayer. The association of PC and PE in the membrane affecting the reorientation of the P-N groups is dependent of the chain-chain interaction. The dipole potentials of PCs and PEs mixtures show different behaviors according to the saturation of the acyl chain. This was correlated with the area in monolayers and the hydration of the P-N groups. In spite of the low hydration, DMPE is still able to adsorb fully hydrated proteins, although in a lower rate than DMPC at the same surface pressure. This indicates that PE interfaces possess an excess of surface free energy to drive protein interaction. The relation of this free energy with the low water content is discussed.
Assuntos
Lipídeos de Membrana/química , Fosfatidiletanolaminas/química , Adsorção , Animais , Fenômenos Biofísicos , Técnicas In Vitro , Lecitinas/química , Potenciais da Membrana , Membranas Artificiais , Micelas , Estrutura Molecular , Pressão , Proteínas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , TermodinâmicaRESUMO
The scope of the present review focuses on the interfacial properties of cell membranes that may establish a link between the membrane and the cytosolic components. We present evidences that the current view of the membrane as a barrier of permeability that contains an aqueous solution of macromolecules may be replaced by one in which the membrane plays a structural and functional role. Although this idea has been previously suggested, the present is the first systematic work that puts into relevance the relation water-membrane in terms of thermodynamic and structural properties of the interphases that cannot be ignored in the understanding of cell function. To pursue this aim, we introduce a new definition of interphase, in which the water is organized in different levels on the surface with different binding energies. Altogether determines the surface free energy necessary for the structural response to changes in the surrounding media. The physical chemical properties of this region are interpreted in terms of hydration water and confined water, which explain the interaction with proteins and could affect the modulation of enzyme activity. Information provided by several methodologies indicates that the organization of the hydration states is not restricted to the membrane plane albeit to a region extending into the cytoplasm, in which polar head groups play a relevant role. In addition, dynamic properties studied by cyclic voltammetry allow one to deduce the energetics of the conformational changes of the lipid head group in relation to the head-head interactions due to the presence of carbonyls and phosphates at the interphase. These groups are, apparently, surrounded by more than one layer of water molecules: a tightly bound shell, that mostly contributes to the dipole potential, and a second one that may be displaced by proteins and osmotic stress. Hydration water around carbonyl and phosphate groups may change by the presence of polyhydroxylated compounds or by changing the chemical groups esterified to the phosphates, mainly choline, ethanolamine or glycerol. Thus, surface membrane properties, such as the dipole potential and the surface pressure, are modulated by the water at the interphase region by changing the structure of the membrane components. An understanding of the properties of the structural water located at the hydration sites and the functional water confined around the polar head groups modulated by the hydrocarbon chains is helpful to interpret and analyze the consequences of water loss at the membranes of dehydrated cells. In this regard, a correlation between the effects of water activity on cell growth and the lipid composition is discussed in terms of the recovery of the cell volume and their viability. Critical analyses of the properties of water at the interface of lipid membranes merging from these results and others from the literature suggest that the interface links the membrane with the aqueous soluble proteins in a functional unit in which the cell may be considered as a complex structure stabilized by water rather than a water solution of macromolecules surrounded by a semi permeable barrier.