83 research outputs found

    Prefrontal glutamate correlates of methamphetamine sensitization and preference.

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    Methamphetamine (MA) is a widely misused, highly addictive psychostimulant that elicits pronounced deficits in neurocognitive function related to hypo-functioning of the prefrontal cortex (PFC). Our understanding of how repeated MA impacts excitatory glutamatergic transmission within the PFC is limited, as is information about the relationship between PFC glutamate and addiction vulnerability/resiliency. In vivo microdialysis and immunoblotting studies characterized the effects of MA (ten injections of 2 mg/kg, i.p.) upon extracellular glutamate in C57BL/6J mice and upon glutamate receptor and transporter expression, within the medial PFC. Glutamatergic correlates of both genetic and idiopathic variance in MA preference/intake were determined through studies of high vs. low MA-drinking selectively bred mouse lines (MAHDR vs. MALDR, respectively) and inbred C57BL/6J mice exhibiting spontaneously divergent place-conditioning phenotypes. Repeated MA sensitized drug-induced glutamate release and lowered indices of N-methyl-d-aspartate receptor expression in C57BL/6J mice, but did not alter basal extracellular glutamate content or total protein expression of Homer proteins, or metabotropic or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors. Elevated basal glutamate, blunted MA-induced glutamate release and ERK activation, as well as reduced protein expression of mGlu2/3 and Homer2a/b were all correlated biochemical traits of selection for high vs. low MA drinking, and Homer2a/b levels were inversely correlated with the motivational valence of MA in C57BL/6J mice. These data provide novel evidence that repeated, low-dose MA is sufficient to perturb pre- and post-synaptic aspects of glutamate transmission within the medial PFC and that glutamate anomalies within this region may contribute to both genetic and idiopathic variance in MA addiction vulnerability/resiliency

    Nuclear spin relaxation and translational diffusion study of Benzene-Hexa-n-alkanoat

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    The molecular dynamics of benzene-hexa-n-heptanoate (BHA7) have been studied in the isotropic liquid phase by multified carbon-13 nuclear spin relaxation of a carboxyl carbon labeled compound. The experimental data are analyzed with a dynamical model based on the assumption of three trypes of motion: a fast internal motion in the aliphatic chains, a slow overall reorientation of the molecule, and an intermediate process connected with the flexibility of the carboxyl group. The first two motions occur clearly on different time scales, whereas the last process is not time scale separated from the global molecular tumbling. Preciously reported carbon-13 line shapes in the mesophase and in the solid state of BHA7 were used for vertification of the results. Measurements of translational diffusion coefficients in isotropic and ordered phases of BHA6 and BHA7 were performed using 1H pulsed field gradient NMR spin-echo techniques

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    13C NMR studies of columnar liquid crystals

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    Many materials composed of disc-shaped molecules exhibit thermotropic liquid crystalline phases. Most of the mesophases formed by these molecules display an architecture where the molecules are stacked into columns, which in turn form two-dimensional arrays. These columnar phases, which have gained much attention due to the potentially important practical applications, particularly in electronics and display technology, are currently under active studies by various experimental techniques, including nuclear magnetic resonance (NMR). Carbon-13 NMR spectroscopy is an increasingly important tool in studies of columnar liquid crystals. The method is a useful complement to the traditional 2H NMR approach, which requires isotopic labeling and may be difficult to realize due to problems with spectral assignment and overlap. By employing advanced 13C NMR methods developed during the last decade, it is now possible to extract very detailed information on molecular structure, order and dynamics from multi-dimensional 13C NMR experiments in oriented as well as in unoriented mesophases under both static and magic-angle spinning (MAS) conditions. In this chapter, we demonstrate applications of recently developed NMR methods to columnar liquid crystals. Several techniques are considered; in particular we describe experimental methods for signal enhancement, spectral assignment, determination of the chemical shift anisotropies, and measurement of dipolar couplings. The efficiency and accuracy of the various approaches are also discussed

    13C-detected 1H–2H separated local field NMR spectroscopy

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    We present a new NMR method for measuring 1H–2H dipolar couplings in macroscopically oriented media. To overcome the lack of dipolar resolution in 1D 1H and 2H spectra of deuterated molecules, we use a 2D heteronuclear correlation experiment where 1H chemical shifts and 1H–2H dipolar interactions in the first dimension are correlated with 13C chemical shifts and 2H–13C dipolar interactions in the second dimension. The technique is demonstrated on a columnar liquid-crystalline phase
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