Characterization of dopaminergic projections from the ventral tegmental area and the dorsal raphe nucleus to the orbital frontal cortex.

The orbitofrontal cortex (OFC) is a key node in the cortico-limbic-striatal circuitry that influences decision-making guided by the relative value of outcomes. Midbrain dopamine from either the ventral tegmental area (VTA) or the dorsal raphe nucleus (DRN) has the potential to modulate OFC neurons; however, it is unknown at what concentrations these terminals release dopamine. Male and female adult dopamine transporter (DAT)IRES-Cre-tdTomato mice were injected with AAV2/8-EF1a-DIO-eYFP into either the DRN or the VTA or the retrograde label cholera toxin B (CTB) 488 in the medial or lateral OFC. We quantified co-expression of CTB 488 or enhanced yellow fluorescent protein (eYFP) with tdTomato fluorescence in VTA or DRN and eYFP fibre density in the medial or lateral OFC. Both VTA and DRN dopamine neurons project to either the medial OFC or the lateral OFC, with greater expression of fibres in the medial OFC. Using fast-scan cyclic voltammetry, we detected optogenetically evoked dopamine from channelrhodopsin 2 (ChR2)-expressing VTA or DRN dopamine terminals in either the medial OFC or the lateral OFC. We assessed if optical stimulation of dopamine from the VTA or the DRN onto the medial OFC could alter layer V pyramidal neuronal firing; however, we did not observe a change in firing at stimulation parameters that evoked dopamine release from either projection even though bath application of dopamine with the monoamine transporter inhibitor, nomifensine, decreased firing. In summary, dopaminergic neurons from the VTA or the DRN project to the OFC and release submicromolar dopamine in the medial and lateral OFC.

Crystal structure of (1S,2S,5R)-5-acetyl-amino-4-oxo-2,3-diphenyl-1,3-thia-zinan-1-ium-1-olate.

The asymmetric unit of the enanti-omerically pure title compound, C18H18N2O3S, comprises two independent mol-ecules (A and B) having almost identical conformations. When overlayed, the alignment-r.m.s. deviation value is 0.30 Å. The six-membered heterocycle has a twisted half-chair conformation in both mol-ecules. The O atom on the S atom of the ring is pseudo-axial on the thia-zine ring and trans to both a phenyl group substituent and the acetamide group in each case. The two benzene rings in each mol-ecule are almost orthogonal to each other, with inter-planar dihedral angles of 83.79 (17) and 86.95 (16)°. The acetamide group is pseudo-equatorial and a phenyl ring is pseudo-axial on the thia-zine ring. Both mol-ecules show a weak intra-molecular C-H⋯O inter-action between H-atom donors of one of the phenyl rings and the acetamide group. In the crystal, an inter-molecular N-H⋯O(thia-zine) hydrogen bond links B mol-ecules along the 21 (b) screw axis and, in addition, an N-H⋯O(acetamide) hydrogen bond links A and B mol-ecules across a. A two-dimensional layered structure lying parallel to (001) is generated, also involving weak inter-molecular C-H⋯O inter-actions.

Crystal structures of three substituted 3-aryl-2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-ones.

Three ring-substituted 3-aryl analogs of 2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one, namely 3-(4-meth-oxy-phen-yl)-2-phenyl-4H-1,3-benzo-thia-zin-4-one, C21H17NO2S, (I), 2-phenyl-3-[4-(tri-fluoro-meth-yl)phen-yl]-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one toluene hemisolvate, C21H14F3NOS·0.5C7H8, (II), and 3-(3-bromo-phen-yl)-2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one toluene hemisolvate, C20H14BrNOS·0.5C7H8, (III), were synthesized and their crystal structures determined. The hemisolvates differ in that in (II), the asymmetric unit comprises two molecules of the benzo-thia-zinone compound and a toluene solvent mol-ecule, whereas in (III), the unit comprises one benzo-thia-zinone mol-ecule and a half-occupancy toluene solvent mol-ecule. All crystals are of racemic mixtures of the chiral 2-C atom of the thia-zine moiety, which in all structures has a screw-boat puckering, with the puckering amplitude values within the range 0.575-0.603 Å. In all three structures, the benzene plane of the benzo-thia-zine system makes a dihedral angle in the range 78.60 (5) to 98.40 (5)° with the unsubstituted benzene plane and in the range 70.50 (1) to 121.00 (5)° with the substituted benzene plane. The CF3 substituent group in one of the mol-ecules of (II) shows positional disorder, with an occupancy ratio of 0.57 (3):0.43 (3). In the crystals of (I) and (II), weak inter-molecular C-H⋯O inter-actions are present, giving in (I), mol-ecules arranged in a plane parallel to (010), and in (II), chains along a. In addition, all three structures show weak C-H⋯π inter-actions involving various aromatic rings.