Addiction Rehab: PET Imaging of Metabotropic Glutamate Receptor Subtype 5 (MGluR5).

PET imaging of metabotropic glutamate receptor subtype 5 (mGluR5).

Filed under: Addiction Rehab

Am J Nucl Med Mol Imaging. 2012; 2(1): 29-32
Li D, Shan H, Conti P, Li Z

Metabotropic glutamate receptors (mGluRs) belong to a family of G-protein coupled receptors involved in the modulation of fast excitatory transmission. In particular, the subtype-5 receptor (mGluR5) was found to be an attractive target for the treatment and diagnosis of variety of psychiatric and neurological disease including anxiety, depression, epilepsy, drug addiction, and Parkinson’s disease. Positron emission tomography (PET) is a highly sensitive imaging technique that holds great potential for the diagnosis of a brain disorder. In the study published in the American Journal of Nuclear Medicine and Molecular Imaging, a (18)F labelled PET probe was developed targeting mGluR5. This paper represents the efforts and challenges on the design and development of novel PET tracers for mGluR5 imaging.
HubMed – addiction


Motivational Mechanisms and Outcome Expectancies Underlying the Approach Bias toward Addictive Substances.

Filed under: Addiction Rehab

Front Psychol. 2012; 3: 440
Watson P, de Wit S, Hommel B, Wiers RW

Human behavior can be paradoxical, in that actions can be initiated that are seemingly incongruent with an individual’s explicit desires. This is most commonly observed in drug addiction, where maladaptive behavior (i.e., drug seeking) appears to be compulsive, continuing at great personal cost. Approach biases toward addictive substances have been correlated with actual drug-use in a number of studies, suggesting that this measure can, in some cases, index everyday maladaptive tendencies. At present it is unclear whether this bias to drug cues is a Pavlovian conditioned approach response, a habitual response, the result of a Pavlovian-instrumental transfer process, or a goal-directed action in the sense that expectancy of the rewarding effects of drugs controls approach. We consider this question by combining the theoretical framework of associative learning with the available evidence from approach bias research. Although research investigating the relative contributions of these mechanisms to the approach bias is to date relatively limited, we review existing studies and also outline avenues for future research.
HubMed – addiction


The dynamics of somatic exocytosis in monoaminergic neurons.

Filed under: Addiction Rehab

Front Physiol. 2012; 3: 414
Sarkar B, Das AK, Arumugam S, Kaushalya SK, Bandyopadhyay A, Balaji J, Maiti S

Some monoaminergic neurons can release neurotransmitters by exocytosis from their cell bodies. The amount of monoamine released by somatic exocytosis can be comparable to that released by synaptic exocytosis, though neither the underlying mechanisms nor the functional significance of somatic exocytosis are well understood. A detailed examination of these characteristics may provide new routes for therapeutic intervention in mood disorders, substance addiction, and neurodegenerative diseases. The relatively large size of the cell body provides a unique opportunity to understand the mechanism of this mode of neuronal exocytosis in microscopic detail. Here we used three photon and total internal reflection fluorescence microscopy to focus on the dynamics of the pre-exocytotic events and explore the nature of somatic vesicle storage, transport, and docking at the membrane of serotonergic neurons from raphe nuclei of the rat brain. We find that the vesicles (or unresolved vesicular clusters) are quiescent (mean square displacement, MSD ?0.04??m(2)/s) before depolarization, and they move minimally (<1??m) from their locations over a time-scale of minutes. However, within minutes of depolarization, the vesicles become more dynamic (MSD ?0.3??m(2)/s), and display larger range (several ?m) motions, though without any clear directionality. Docking and subsequent exocytosis at the membrane happen at a timescale (?25?ms) that is slower than most synaptic exocytosis processes, but faster than almost all somatic exocytosis processes observed in endocrine cells. We conclude that, (A) depolarization causes de-tethering of the neurotransmitter vesicles from their storage locations, and this constitutes a critical event in somatic exocytosis; (B) their subsequent transport kinetics can be described by a process of constrained diffusion, and (C) the pre-exocytosis kinetics at the membrane is faster than most other somatic exocytosis processes reported so far. HubMed – addiction


Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain.

Filed under: Addiction Rehab

Front Pharmacol. 2012; 3: 185
Biegon A, Alia-Klein N, Fowler JS

Cigarette smoking continues to be a major public health problem, and while smoking rates in men have shown some decrease over the last few decades, smoking rates among girls and young women are increasing. Practically all of the important aspects of cigarette smoking and many effects of nicotine are sexually dimorphic (reviewed by Pogun and Yararbas, 2009). Women become addicted more easily than men, while finding it harder to quit. Nicotine replacement appears to be less effective in women. This may be linked to the observation that women are more sensitive than men to non-nicotine cues or ingredients in cigarettes. The reasons for these sex differences are mostly unknown. Several lines of evidence suggest that many of the reported sex differences related to cigarette smoking may stem from the inhibitory effects of nicotine and other tobacco alkaloids on estrogen synthesis via the enzyme aromatase (cyp19a gene product). Aromatase is the last enzyme in estrogen biosynthesis, catalyzing the conversion of androgens to estrogens. This review provides a summary of experimental evidence supporting brain aromatase as a potential mediator and/or modulator of nicotine actions in the brain, contributing to sex differences in smoking behavior. Additional research on the interaction between tobacco smoke, nicotine, and aromatase may help devise new, sex specific methods for prevention and treatment of smoking addiction.
HubMed – addiction



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