Increased cocaine self-administration in rats lacking the serotonin transporter : a role for glutamatergic signaling in the habenula

Serotonin (5-HT) and the habenula (Hb) contribute to motivational and emotional states such as depression and drug abuse. The dorsal raphe nucleus, where 5-HT neurons originate, and the Hb are anatomically and reciprocally interconnected. Evidence exists that 5-HT influences Hb glutamatergic transmission. Using serotonin transporter knockout (SERT-/- ) rats, which show depression-like behavior and increased cocaine intake, we investigated the effect of SERT reduction on expression of genes involved in glutamate neurotransmission under both baseline conditions as well as after short-access or long-access cocaine (ShA and LgA, respectively) intake. In cocaine-na\uefve animals, SERT removal led to reduced baseline Hb mRNA levels of critical determinants of glutamate transmission, such as SLC1A2, the main glutamate transporter and N-methyl-D-aspartate (Grin1, Grin2A and Grin2B) as well as \u3b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (Gria1 and Gria2) receptor subunits, with no changes in the scaffolding protein Dlg4. In response to ShA and LgA cocaine intake, SLC1A2 and Grin1 mRNA levels decreased in SERT+/+ rats to levels equal of those of SERT-/- rats. Our data reveal that increased extracellular levels of 5-HT modulate glutamate neurotransmission in the Hb, serving as critical neurobiological substrate for vulnerability to cocaine addiction

Aversive Counterconditioning Attenuates Reward Signaling in the Ventral Striatum

Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient reward such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional magnetic resonance imaging (fMRI). In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signaling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signaling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes : A systematic review and meta-analyses of animal studies

Funding Information: This work was supported by a ZonMw grant (MKMD project; ID 114024127 ) awarded to JO & AR, and a grant awarded to JH from the Donders Institute for Brain, Cognition and Behavior . Funding bodies had no role in study design, data collection, data analysis, data interpretation, or the writing of the report.Peer reviewedPublisher PD

Six state molecular revolver mounted on a rigid platform

The rotation of entire molecules or large moieties happens at 100 ps time scales and the transition process itself is experimentally inaccessible to scanning probe techniques. However, the reversible switching of a molecule between more than two metastable states allows to assign a rotational switching direction. Rotational switching is a phenomenon that is particularly interesting with regard to possible applications in molecular motors. In this work, single tetraphenylmethane molecules deposited on a Au(111) surface were studied in a low temperature scanning tunneling microscope (STM). These molecules comprise rotational axes mounted on a tripodal sulfur-anchored stand and with the STM tip, we were able to induce transitions between six rotational states of the molecular motif. We were able to identify critical parameters for the onset of rotational switching and to characterize the influence of the local environment. The subtle difference between fcc and hcp stacking and the rotational state of neighboring molecules clearly influence the population of the rotational states

Factors Affecting the Clinical Measurement of Visuo-Spatial Neglect

The present study examined a battery of tests to evaluate unilateral spatial neglect; the tests included different tasks involving several modalities of spatial exploration mapping perceptual, motor, attentional and personal or extrapersonal space dimensions. The subjects, 121 right-brain-damaged patients with unilateral neglect, were studied in seven laboratories in four European countries. Relationships among the various tests were examined by correlations, a cluster analysis and by an analysis of individual cases. Different sensitivity was found among various tests for detecting neglect performances. Both the cluster analysis and the single case analysis clearly showed a segregation between personal and extrapersonal neglect. Analysis of the large cluster, including a variety of tests of extra personal neglect, together with the study of single cases, suggests the possibility of differentiating the various manifestations of spatial neglect which can be interpreted on the basis of the descriptions of other individual cases previously reported in the literature. Finally, the present study indicated the relative stability of neglect following the acute phase and its independence from age

Патопсихологические особенности и закономерности развития органических психических расстройств при болезни Паркинсона

Проанализированы особенности эмоционально−потребностной сферы, выраженность личностных особенностей, типы отношения к болезни у пациентов с болезнью Паркинсона (БП) и психическими расстройствами. Выявлены патопсихологические факторы формирования органического депрессивного расстройства (F06.36), органического тревожного расстройства (F06.4), органического эмоционально−лабильного расстройства (F06.6), описаны механизмы их патогенеза. Относительно деменции (F02.3) у больных БП единого патопсихологического механизма ее формирования не обнаружено, основная роль в ее патогенезе принадлежит органическому поражению головного мозга.Проаналізовано особливості емоційно−потребової сфери, виразність особистісних особливостей, типи ставлення до хвороби у пацієнтів із хворобою Паркінсона (ХП) та психічними розладами. Виявлено патопсихологічні фактори формування органічного депресивного розладу (F06.36), органічного тривожного розладу (F06.4), органічного емоційно−лабільного розладу (F06.6), описано механізми їх патогенезу. Щодо деменції (F02.3) у хворих на ХП єдиного патопсихологічного механізму її формування не виявлено, основна роль в її патогенезі належить органічному ураженню головного мозку.The peculiarities of emotion−need sphere, degree of personality peculiarities, types of attitude to the disease were analyzed in patients with Parkinson's disease (PD) and mental disorders. Pathopsychological factors of forming organic depressive disorder (F06.36), organic anxiety disorder (F06.4), organic emotional−labile disorder (F06.6) were revealed. The mechanisms of their pathogenesis were described. As for dementia (F02.3), uniform pathopsychological mechanism of its formation was not revealed in patients with PD. Main role in its pathogenesis is played by organic brain lesions

Competition-based model of pheromone component ratio detection in the moth

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy