Monoaminergic and Neuropeptidergic Neurons Have Distinct Expression Profiles of Histone Deacetylases.

Monoaminergic and neuropeptidergic neurons have distinct expression profiles of histone deacetylases.

PLoS One. 2013; 8(3): e58473
Takase K, Oda S, Kuroda M, Funato H

Monoaminergic and neuropeptidergic neurons regulate a wide variety of behaviors, such as feeding, sleep/wakefulness behavior, stress response, addiction, and social behavior. These neurons form neural circuits to integrate different modalities of behavioral and environmental factors, such as stress, maternal care, and feeding conditions. One possible mechanism for integrating environmental factors through the monoaminergic and neuropeptidergic neurons is through the epigenetic regulation of gene expression via altered acetylation of histones. Histone deacetylases (HDACs) play an important role in altering behavior in response to environmental factors. Despite increasing attention and the versatile roles of HDACs in a variety of brain functions and disorders, no reports have detailed the localization of the HDACs in the monoaminergic and neuropeptidergic neurons. Here, we examined the expression profile of the HDAC protein family from HDAC1 to HDAC11 in corticotropin-releasing hormone, oxytocin, vasopressin, agouti-related peptide (AgRP), pro-opiomelanocortin (POMC), orexin, histamine, dopamine, serotonin, and noradrenaline neurons. Immunoreactivities for HDAC1,-2,-3,-5,-6,-7,-9, and -11 were very similar among the monoaminergic and neuropeptidergic neurons, while the HDAC4, -8, and -10 immunoreactivities were clearly different among neuronal groups. HDAC10 expression was found in AgRP neurons, POMC neurons, dopamine neurons and noradrenaline neurons but not in other neuronal groups. HDAC8 immunoreactivity was detected in the cytoplasm of almost all histamine neurons with a pericellular pattern but not in other neuropeptidergic and monoaminergic neurons. Thus, the differential expression of HDACs in monoaminergic and neuropeptidergic neurons may be crucial for the maintenance of biological characteristics and may be altered in response to environmental factors. HubMed – addiction


Altered reward circuitry in the norepinephrine transporter knockout mouse.

PLoS One. 2013; 8(3): e57597
Gallagher JJ, Zhang X, Hall FS, Uhl GR, Bearer EL, Jacobs RE

Synaptic levels of the monoamine neurotransmitters dopamine, serotonin, and norepinephrine are modulated by their respective plasma membrane transporters, albeit with a few exceptions. Monoamine transporters remove monoamines from the synaptic cleft and thus influence the degree and duration of signaling. Abnormal concentrations of these neuronal transmitters are implicated in a number of neurological and psychiatric disorders, including addiction, depression, and attention deficit/hyperactivity disorder. This work concentrates on the norepinephrine transporter (NET), using a battery of magnetic resonance imaging techniques and histological correlates to probe the effects of genetic deletion of the norepinephrine transporter on brain metabolism, anatomy and functional connectivity. MRS recorded in the striatum of NET knockout mice indicated a lower concentration of NAA that correlates with histological observations of subtle dysmorphisms in the striatum and internal capsule. As with DAT and SERT knockout mice, we detected minimal structural alterations in NET knockout mice by tensor-based morphometric analysis. In contrast, longitudinal imaging after stereotaxic prefrontal cortical injection of manganese, an established neuronal circuitry tracer, revealed that the reward circuit in the NET knockout mouse is biased toward anterior portions of the brain. This is similar to previous results observed for the dopamine transporter (DAT) knockout mouse, but dissimilar from work with serotonin transporter (SERT) knockout mice where Mn tracings extended to more posterior structures than in wildtype animals. These observations correlate with behavioral studies indicating that SERT knockout mice display anxiety-like phenotypes, while NET knockouts and to a lesser extent DAT knockout mice display antidepressant-like phenotypic features. Thus, the mainly anterior activity detected with manganese-enhanced MRI in the DAT and NET knockout mice is likely indicative of more robust connectivity in the frontal portion of the reward circuit of the DAT and NET knockout mice compared to the SERT knockout mice. HubMed – addiction


Profile of Substance Use among Patients Attending De-Addiction Centres in a Coastal City of Southern India.

PLoS One. 2013; 8(2): e57824
Kumar N, Kanchan T, Unnikrishnan B, Thapar R, Mithra P, Kulkarni V, Papanna MK, Holla R, Sarathy S

Drug dependence is still to be recognized in developing countries as a significant public health problem and literature on the magnitude of this problem is limited. The present research was planned to study the socio-demographic profile and the reasons for substance use among patients admitted at De-addiction centres in Mangalore, India. In this cross-sectional study, all the patients admitted at the De-addiction centres during the study period were interviewed. The data was analyzed and the results obtained were expressed in proportions. A total of 83 patients were included in the study, all of whom were males. A positive family history of substance use was evident in 63% of the respondents. The mean age of the study participants was 41.9 (SD±11.2) years and the mean age for starting substance use was 20.9 (SD±7.7) years. The most common substance used was alcohol (95.2%). Majority of the subjects (56.6%) cited peer pressure as a reason for initiating substance use. Our findings suggest that the initiation of substance use occurs during late teenage years and mostly due to peer pressure. Our observations point towards the vulnerability of younger age towards substance use and hence, it is proposed that the preventive health policies in this regard should be targeted specifically during teenage years. HubMed – addiction


Development and Validation of a Smartphone Addiction Scale (SAS).

PLoS One. 2013; 8(2): e56936
Kwon M, Lee JY, Won WY, Park JW, Min JA, Hahn C, Gu X, Choi JH, Kim DJ

The aim of this study was to develop a self-diagnostic scale that could distinguish smartphone addicts based on the Korean self-diagnostic program for Internet addiction (K-scale) and the smartphone’s own features. In addition, the reliability and validity of the smartphone addiction scale (SAS) was demonstrated.A total of 197 participants were selected from Nov. 2011 to Jan. 2012 to accomplish a set of questionnaires, including SAS, K-scale, modified Kimberly Young Internet addiction test (Y-scale), visual analogue scale (VAS), and substance dependence and abuse diagnosis of DSM-IV. There were 64 males and 133 females, with ages ranging from 18 to 53 years (M?=?26.06; SD?=?5.96). Factor analysis, internal-consistency test, t-test, ANOVA, and correlation analysis were conducted to verify the reliability and validity of SAS.Based on the factor analysis results, the subscale “disturbance of reality testing” was removed, and six factors were left. The internal consistency and concurrent validity of SAS were verified (Cronbach’s alpha?=?0.967). SAS and its subscales were significantly correlated with K-scale and Y-scale. The VAS of each factor also showed a significant correlation with each subscale. In addition, differences were found in the job (p<0.05), education (p<0.05), and self-reported smartphone addiction scores (p<0.001) in SAS.This study developed the first scale of the smartphone addiction aspect of the diagnostic manual. This scale was proven to be relatively reliable and valid. HubMed – addiction