Photodissociation studies of the CH2OD radical in the region 28,000-41,000 cm(-1) (357-244 nm), which includes excitation to the 3s, 3p(x), and 3p(z) states, are reported. H and D photofragments are monitored by using resonance-enhanced multiphoton ionization (REMPI) from the onset of H formation at approximately 30,500 cm(-1) to the origin band region of the 3pz(2A")<--1 2A" transition at 41,050 cm(-1). Kinetic energy distributions P(ET) and recoil anisotropy parameters as a function of kinetic energy, beta(eff)(ET), are determined by the core sampling technique for the channels producing H and D fragments. Two dissociation channels are identified: (I) D+CH2O and (II) H+CHOD. The contribution of channel II increases monotonically as the excitation energy is increased. Based on the calculations of Hoffmann and Yarkony [J. Chem. Phys. 116, 8300 (2002)], it is concluded that conical intersections between 3s and the ground state determine the final branching ratio even when initial excitation accesses the 3px) and 3pz states. The different beta(eff) values obtained for channels I and II (-0.7 and approximately 0.0, respectively) are attributed to the different extents of out-of-plane nuclear motions in the specific couplings between 3s and the ground state (of A' and A'' symmetry, respectively) that lead to each channel. The upper limit to the dissociation energy of the C-H bond, determined from P(ET), is D0(C-H)=3.4+/-0.1 eV (79+/-2 kcal/mol). Combining this value with the known heats of formation of H and CH2OD, the heat of formation of CHOD is estimated at DeltaHf(0)(CHOD)=24+/-2 kcal/mol.

The photodissociation of the deuterated hydroxymethyl radical CH 2 OD is investigated on the lowest excited state, the 3s Rydberg state, in the wavelength region 365-318 nm where the D atom is the only significant product. The translational energy distribution and kinetic energy-dependent anisotropy parameter of the D channel are determined by the core-sampling time-of-flight technique at 352.5 nm. The negative recoil anisotropy parameter ␤ eff ϭϪ0.7Ϯ0.1 is consistent with the perpendicular nature of the transition from the ground state. The fraction of the available energy partitioned into the translational degree of freedom is 0.69. Ground state products CH 2 O (1 1 A 1) ϩD constitute the main photodissociation channel, and no significant H product is detected at these wavelengths. Comparison with the conical intersection calculations of Hoffman and Yarkony suggests that O-D bond rupture involves crossing from the 3s potential energy surface to a repulsive region of the ground state surface at a large O-D bond distance. Isomerization of CH 2 OD to CH 2 DO is not competitive with the fast O-D dissociation.

The use of pharmacologic MRI (phMRI) in mouse models of brain disorders allows noninvasive in vivo assessment of drug-modulated local cerebral blood volume changes (ΔCBV) as one correlate of neuronal and neuro-vascular activities. In this report, we employed CBV weighted phMRI to compare cocaine-modulated neuronal activity in dopamine transporter (DAT) knockout (KO) and wild-type mice. Cocaine acts to block the dopamine, norepinephrine and serotonin transporters (DAT, NET and SERT) that clear their respective neurotransmitters from the synapses, helping to terminate cognate neurotransmission. Cocaine consistently reduced CBV, with a similar pattern of regional ΔCBV in brain structures involved in mediating reward in both DAT genotypes. The largest effects (−20% to −30% ΔCBV) were seen in the nucleus accumbens and several cortical regions. Decreasing response amplitudes to cocaine were noted in more posterior components of the cortico-mesolimbic circuit. DAT KO mice had significantly attenuated ΔCBV amplitudes, shortened times to peak response and reduced response duration in most regions. This study demonstrates that DAT knockout does not abolish the phMRI responses to cocaine, suggesting that adaptations to loss of DAT and/or retained cocaine activity in other monoamine neurotransmitter systems underlie these responses in DAT KO mice.

Pharmacologic MRI (phMRI) uses functional MRI techniques to provide a non-invasive in vivo measurement of the hemodynamic effects of drugs. The cerebral blood volume change (ΔCBV) serves as a surrogate for neuronal activity via neurovascular coupling mechanisms. By assessing the location and time course of brain activity in mouse mutant studies, phMRI can provide valuable insights into how different behavioral phenotypes are expressed in differing brain activity response to drug challenge. In this report, we evaluate the utility of three different intravascular ultrasmall superparamagnetic iron oxide (USPIO) contrast agents for phMRI using a gradient-echo technique with temporal resolution of one minute at high magnetic field. The tissue half life of the USPIOs was studied using a nonlinear detrending model. All three studied USPIOs are candidates for CBV weighted phMRI-experiments, with r2/r1 ratios ≥ 20 and apparent half-lives ≥ 1.5 h at the described doses. An echo time of about 10 ms or longer results in a fCNR > 75 after USPIO injection, with negligible decrease during 1.5 to 2 hours. phMRI experiments were conducted at 7T using cocaine as a psychotropic substance and acetazolamide, a global vasodilator, as a positive control. Cocaine acts as a dopamine-serotonin-norepinephrine reuptake inhibitor, increasing extracellular concentrations of these neurotransmitters and thus increasing dopaminergic, serotonergic and noradrenergic neurotransmission. phMRI indicated that CBV was reduced in the normal mouse brain after cocaine challenge, with largest effects in nucleus accumbens, while after acetazolamide the blood volume was increased in both cerebral and extra-cerebral tissue.