Effects of smoking cessation on presynaptic dopamine function of addicted male smokers

Background There is evidence of abnormal cerebral dopamine transmission in nicotine-dependent smokers, but it is unclear whether dopaminergic abnormalities are due to acute nicotine abuse or whether they persist with abstinence. We addressed this question by conducting longitudinal positron emission tomography (PET) examination of smokers before and after 3 months of abstinence.MethodsWe obtained baseline 6-[18F]fluoro-L-DOPA (FDOPA)-PET scans in 15 nonsmokers and 30 nicotine-dependent smokers, who either smoked as per their usual habit or were in acute withdrawal. All smokers then underwent cessation treatment, and successful abstainers were re-examined by FDOPA-PET after 3 months of abstinence (n = 15). Uptake of FDOPA was analyzed using a steady-state model yielding estimates of the dopamine synthesis capacity (K); the turnover of tracer dopamine formed in living brain (kloss); and the tracer distribution volume (Vd), which is an index of dopamine storage capacity.ResultsCompared with nonsmokers, K was 15% to 20% lower in the caudate nuclei of consuming smokers. Intraindividual comparisons of consumption and long-term abstinence revealed significant increases in K in the right dorsal and left ventral caudate nuclei. Relative to acute withdrawal, Vd significantly decreased in the right ventral and dorsal caudate after prolonged abstinence. Severity of nicotine dependence significantly correlated with dopamine synthesis capacity and dopamine turnover in the bilateral ventral putamen of consuming smokers.ConclusionsThe results suggest a lower dopamine synthesis capacity in nicotine-dependent smokers that appears to normalize with abstinence. Further investigations are needed to clarify the role of dopamine in nicotine addiction to help develop smoking prevention and cessation treatments

Xenopus Xlmo4 is a GATA cofactor during ventral mesoderm formation and regulates Ldb1 availability at the dorsal mesoderm and the neural plate

19 páginas, 7 figuras.We have identified and functionally characterized the Xenopus Xlmo4 gene, which encodes a member of the LIM-domain-only protein family. Xlmo4 is activated at gastrula stages in the mesodermal marginal zone probably in response to BMP4 signaling. Soon after, Xlmo4 is downregulated in the dorsal region of the mesoderm. This repression seems to be mediated by organizer-expressed repressors, such as Gsc. Xlmo4 downregulation is necessary for the proper formation of this territory. Increasing Xlmo4 function in this region downregulates Spemman Organizer genes and suppresses dorsal-anterior structures. By binding to Ldb1, Xlmo4 may restrict the availability of this cofactor for transcription factors expressed at the Spemman Organizer. In the ventral mesoderm, Xlmo4 is required to establish the identity of this territory by acting as a positive cofactor of GATA factors. In the neural ectoderm, Xlmo4 expression depends on Xiro homeoprotein activity. In this region, Xlmo4 suppresses differentiation of primary neurons and interferes with gene expression at the Isthmic Organizer, most likely by displacing Ldb1 from active transcription factor complexes required for these processes. Together, our data suggest that Xlmo4 uses distinct mechanisms to participate in different processes during development.Grants from Dirección General de Investigación Científica y Técnica (PB98-0682 and BMC2001-2122 to J.M. and J.L.G.S.), NIH (AR02080 and AR44882 to B.A.), and an institutional grant from Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa are acknowledged.Peer reviewe