Inhibition of Dopamine Transporter Activity by G Protein ?? Subunits.

Inhibition of Dopamine Transporter Activity by G Protein ?? Subunits.

PLoS One. 2013; 8(3): e59788
Garcia-Olivares J, Torres-Salazar D, Owens WA, Baust T, Siderovski DP, Amara SG, Zhu J, Daws LC, Torres GE

Uptake through the Dopamine Transporter (DAT) is the primary mechanism of terminating dopamine signaling within the brain, thus playing an essential role in neuronal homeostasis. Deregulation of DAT function has been linked to several neurological and psychiatric disorders including ADHD, schizophrenia, Parkinson’s disease, and drug addiction. Over the last 15 years, several studies have revealed a plethora of mechanisms influencing the activity and cellular distribution of DAT; suggesting that fine-tuning of dopamine homeostasis occurs via an elaborate interplay of multiple pathways. Here, we show for the first time that the ?? subunits of G proteins regulate DAT activity. In heterologous cells and brain tissue, a physical association between G?? subunits and DAT was demonstrated by co-immunoprecipitation. Furthermore, in vitro pull-down assays using purified proteins established that this association occurs via a direct interaction between the intracellular carboxy-terminus of DAT and G??. Functional assays performed in the presence of the non-hydrolyzable GTP analog GTP-?-S, G?? subunit overexpression, or the G?? activator mSIRK all resulted in rapid inhibition of DAT activity in heterologous systems. G?? activation by mSIRK also inhibited dopamine uptake in brain synaptosomes and dopamine clearance from mouse striatum as measured by high-speed chronoamperometry in vivo. G?? subunits are intracellular signaling molecules that regulate a multitude of physiological processes through interactions with enzymes and ion channels. Our findings add neurotransmitter transporters to the growing list of molecules regulated by G-proteins and suggest a novel role for G?? signaling in the control of dopamine homeostasis. HubMed – addiction


Association between Facebook Dependence and Poor Sleep Quality: A Study in a Sample of Undergraduate Students in Peru.

PLoS One. 2013; 8(3): e59087
Wolniczak I, Cáceres-Delaguila JA, Palma-Ardiles G, Arroyo KJ, Solís-Visscher R, Paredes-Yauri S, Mego-Aquije K, Bernabe-Ortiz A

OBJECTIVES: Internet can accelerate information exchange. Social networks are the most accessed especially Facebook. This kind of networks might create dependency with several negative consequences in people’s life. The aim of this study was to assess potential association between Facebook dependence and poor sleep quality. METHODOLOGYPRINCIPAL FINDINGS: A cross sectional study was performed enrolling undergraduate students of the Universidad Peruana de Ciencias Aplicadas, Lima, Peru. The Internet Addiction Questionnaire, adapted to the Facebook case, and the Pittsburgh Sleep Quality Index, were used. A global score of 6 or greater was defined as the cutoff to determine poor sleep quality. Generalized linear model were used to determine prevalence ratios (PR) and 95% confidence intervals (95%CI). A total of 418 students were analyzed; of them, 322 (77.0%) were women, with a mean age of 20.1 (SD: 2.5) years. Facebook dependence was found in 8.6% (95% CI: 5.9%-11.3%), whereas poor sleep quality was present in 55.0% (95% CI: 50.2%-59.8%). A significant association between Facebook dependence and poor sleep quality mainly explained by daytime dysfunction was found (PR?=?1.31; IC95%: 1.04-1.67) after adjusting for age, sex and years in the faculty. CONCLUSIONS: There is a relationship between Facebook dependence and poor quality of sleep. More than half of students reported poor sleep quality. Strategies to moderate the use of this social network and to improve sleep quality in this population are needed. HubMed – addiction


New treatment gives hope to East Africa’s drug users.

Bull World Health Organ. 2013 Feb 1; 91(2): 89-90

The United Republic of Tanzania is the first mainland sub-Saharan country to launch a national methadone programme as part of its battle to fight the twin epidemics of heroin addiction and HIV infection. Fumbuka Ng’wanakilala reports. HubMed – addiction


Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking.

Nature. 2013 Apr 3;
Chen BT, Yau HJ, Hatch C, Kusumoto-Yoshida I, Cho SL, Hopf FW, Bonci A

Loss of control over harmful drug seeking is one of the most intractable aspects of addiction, as human substance abusers continue to pursue drugs despite incurring significant negative consequences. Human studies have suggested that deficits in prefrontal cortical function and consequential loss of inhibitory control could be crucial in promoting compulsive drug use. However, it remains unknown whether chronic drug use compromises cortical activity and, equally important, whether this deficit promotes compulsive cocaine seeking. Here we use a rat model of compulsive drug seeking in which cocaine seeking persists in a subgroup of rats despite delivery of noxious foot shocks. We show that prolonged cocaine self-administration decreases ex vivo intrinsic excitability of deep-layer pyramidal neurons in the prelimbic cortex, which was significantly more pronounced in compulsive drug-seeking animals. Furthermore, compensating for hypoactive prelimbic cortex neurons with in vivo optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition significantly increased compulsive cocaine seeking. Our results show a marked reduction in prelimbic cortex excitability in compulsive cocaine-seeking rats, and that in vivo optogenetic prelimbic cortex stimulation decreased compulsive drug-seeking behaviours. Thus, targeted stimulation of the prefrontal cortex could serve as a promising therapy for treating compulsive drug use. HubMed – addiction