Antinociception Depends on the Presence of G Protein γ\u3csub\u3e2\u3c/sub\u3e- Subunits in Brain

We have shown previously [Hosohata, K., Logan, J.K., Varga, E., Burkey, T.H., Vanderah, T.W., Porreca, F., Hruby, V.J., Roeske, W.R., Yamamura, H.I., 2000. The role of the G protein γ2 subunit in opioid antinociception in mice. Eur. J. Pharmacol. 392, R9-R11] that intracerebroventricular (i.c.v.) treatment of mice with a phosphorothioate oligodeoxynucleotide antisense to the γ2 subunit (Gγ2) of the heterotrimeric G proteins (antisense ODN) significantly attenuates antinociception by a δ-opioid receptor agonist. In the present study, we examined the involvement of Gγ2 in antinociception mediated by other (μ- or κ-opioid, cannabinoid, α2-adrenoreceptor) analgesic agents in a warm (55°C) water tail-flick test in mice. Interestingly, i.c.v. treatment with the antisense ODN attenuated antinociception by each analgesic agent. Missense phosphorothioate oligodeoxynucleotide treatment, on the other hand, had no effect on antinociception mediated by these agonists. The antinociceptive response recovered in 6 days after the last antisense ODN injection, indicating a lack of nonspecific tissue damage in the animals. These results suggest a pervasive role for the G protein γ2 subunits in supraspinal antinociception

Can Participatory Institutions Promote Pluralism? Mobilizing Low-Income Citizens in Brazil

Participatory decisionmaking institutions have proliferated across the developing world during the past decade as governments and civil society organizations sought to incorporate citizens directly into policymaking arenas. This article draws from a survey (n = 833) of elected delegates in Brazil\u27s Participatory Budgeting (PB) to explain what factors most strongly influence participants\u27 attitudes and behaviors. Do citizen-participants believe that they exercise authority within these new institutions? Have they modified their basic strategies to secure public goods? The purpose of this article is to account for the significant differences in the survey respondents\u27 attitudes and behaviors by developing individual- and municipal-level models that test the significance of civil society participation, institutions, social context, and partisan political identification. Ordinary least squared (OLS) and logistic regression are used to test these models. Group-oriented behavior, more commonly known as pluralism, is replacing clientelism and personalism in the most successful cases of PB due to the extension of authority to individual citizens. This article demonstrates that participatory institutions, in conjunction with participation in a civil society organization, can alter citizens\u27 attitudes and behavior

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

This review summarizes a presentation made at the retirement Symposium of Prof. Dr. Cornelis Jakobs in November of 2011, highlighting the progress toward clinical trials in succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder first recognized in 1981. Active and potential clinical interventions, including vigabatrin, L‐cycloserine, the GHB receptor antagonist NCS‐382, and the ketogenic diet, are discussed. Several biomarkers to gauge clinical efficacy have been identified, including cerebrospinal fluid metabolites, neuropsychiatric testing, MRI, EEG, and measures of GABAergic function including (11 C)flumazenil positron emission tomography (PET) and transcranial magnetic stimulation (TMS). Thirty years after its discovery, encompassing extensive studies in both patients and the corresponding murine model, we are now running an open‐label trial of taurine intervention, and are poised to undertake a phase II trial of the GABAB receptor antagonist SGS742