Benzodiazepines (BZs), which are typically used as anxiolytics, act by modulating inhibitory signaling through gamma-aminobutyric acid A (GABA)(A) receptors. Functionally, the inhibitory effects of GABA may be counterbalanced by the excitatory effects of glutamate (Glu) as the two neurotransmitter systems are metabolically linked through their synthetic intermediate glutamine (Gln). The primary aim of this study was to determine whether the effects of different BZs on the GABA and Glu/Gln systems would vary according to the pharmacokinetics of the different drugs.
View Article and Find Full Text PDFThe cAMP-specific phosphodiesterase PDE4A is abundant in the dendrites, soma and axons of olfactory receptor neurons of the mouse, but it is not present in the cilia, where olfactory transduction initiates. Although the function of PDE4A in mammalian olfaction is unknown, patch clamp studies on deciliated olfactory receptor cells in the newt have shown that adrenaline or cAMP analogs can increase the contrast sensitivity to current injection. We used mice to ask whether increasing the levels of cAMP in sensory neurons by inhibiting PDE4A activity with rolipram could lead to changes in the perception of odorants that correspond to the in vitro cellular responses seen in newts.
View Article and Find Full Text PDFRacemic fluoxetine consists of R- and S-fluoxetine, which are metabolized to R- and S-norfluoxetine, respectively. This study was designed to compare brain levels achieved with R-fluoxetine to those achieved with racemic fluoxetine in healthy subjects using fluorine-19 (19-F) magnetic resonance spectroscopy (MRS). In all, 13 healthy volunteers received study drug for 5 weeks using a dosing schedule designed to achieve steady state for 20 mg/day racemic fluoxetine, 80 mg/day R-fluoxetine, or 120 mg/day R-fluoxetine.
View Article and Find Full Text PDFThough its function remains obscure, olfactory marker protein (OMP) has been implicated in olfactory transduction and the enhancement of neurogenesis within olfactory epithelium. Here we show, using Western blot analysis and immunocytochemistry, that unilateral naris occlusion (UNO) on postnatal day 1 alters OMP immunoreactivity (IR) differentially on the occluded and non-occluded sides of the nasal cavity in 18, 24 and 70-day-old mice. Compared to untreated animals, UNO-treated animals had a decrease in OMP-IR in olfactory receptor neurons on the non-occluded side and an increase in OMP-IR in olfactory receptor neurons on the occluded side of the nasal cavity.
View Article and Find Full Text PDF