Serotonin-3 Receptors in the Posterior Ventral Tegmental Area Regulate Ethanol Self-Administration of Alcohol-Preferring (P) Rats

Several studies indicated the involvement of serotonin-3 (5-HT 3 ) receptors in regulating alcohol- drinking behavior. The objective of this study was to determine the involvement of 5-HT 3 receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers were used to examine the effects of 7 consecutive bilateral micro-infusions of ICS205-930 (ICS), a 5-HT 3 receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (v/v) ethanol self- administration. P rats readily acquired ethanol self-administration by the 4 th session. The three highest doses (0.125, 0.25 and 1.25 ug) of ICS prevented acquisition of ethanol self- administration. During the acquisition post-injection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the 3 highest doses (0.75, 1.0 and 1.25 ug) of ICS significantly increased responding on the ethanol lever; following the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Micro-infusion of ICS into the posterior VTA did not alter the low responding on the water lever, and did not alter saccharin (0.0125% w/v) self-administration.. Micro-infusion of ICS into the anterior VTA did not alter ethanol self- administration. Overall, the results of this study suggest that 5-HT 3 receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration, and/or repeated treatments with a 5-HT 3 receptor antagonist may alter neuronal circuitry within the posterior VTA

Episodic memory and sleep are involved in the maintenance of context-specific lexical information

Familiar words come with a wealth of associated knowledge about their variety of usage, accumulated over a lifetime. How do we track and adjust this knowledge as new instances of a word are encountered? A recent study (Cognition) found that, for homonyms (e.g., bank), sleep-associated consolidation facilitates the updating of meaning dominance. Here, we tested the generality of this finding by exposing participants to (Experiment 1; N = 125) nonhomonyms (e.g., bathtub) in sentences that biased their meanings toward a specific interpretation (e.g., bathtub-slip vs. bathtub-relax), and (Experiment 2; N = 128) word-class ambiguous words (e.g., loan) in sentences where the words were used in their dispreferred word class (e.g., "He will loan me money"). Both experiments showed that such sentential experience influenced later interpretation and usage of the words more after a night's sleep than a day awake. We interpret these results as evidence for a general role of episodic memory in language comprehension such that new episodic memories are formed every time a sentence is comprehended, and these memories contribute to lexical processing next time the word is encountered, as well as potentially to the fine-tuning of long-term lexical knowledge. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Rectifying junctions of tin oxide and poly(3-hexylthiophene) nanofibers fabricated via electrospinning

Abstract: A fast, simple, and inexpensive method to fabricate in air, p-n diodes using electrospun tin oxide nanoribbons and regioregular poly(3-hexylthiophene) nanofibers is described. In addition to being a rectifier under ambient illumination or in the dark, the advantage of our design is the complete exposure of the rectifying nanojunction to the surrounding environment, making them attractive candidates in the potential fabrication of low power consumption diodes and sensors. The diode characteristics were analyzed using the standard diode equation and its use as a UV light sensor was examined

The reinforcing effects of ethanol within the posterior ventral tegmental area depend on dopamine neurotransmission to forebrain cortico-limbic systems

Ethanol can be self-infused directly into the posterior ventral tegmental area (pVTA) and these effects involve activation of local dopamine neurons. However, the neuro-circuitry beyond the pVTA involved in these reinforcing effects has not been explored. Intra-pVTA microinjection of ethanol increases dopamine release in the nucleus accumbens (NAC), medial prefrontal cortex (mPFC) and ventral pallidum (VP). The present study tested the hypothesis that the reinforcing effects of ethanol within the pVTA involve the activation of dopamine projections from the pVTA to the NAC, VP and mPFC. Following the acquisition of self-infusions of 200 mg% ethanol into the pVTA, either the dopamine D2 receptor antagonist sulpiride (0, 10 or 100 μM) or the D1 receptor antagonist SCH-23390 (0, 10 or 100 μM) was microinjected into the ipsilateral NAC shell (NACsh), NAC core (NACcr), VP or mPFC immediately prior to the self-infusion sessions to assess the involvement of the different dopamine projections in the reinforcing effects of ethanol. Microinjection of each compound at higher concentration into the NACsh, VP or mPFC, but not the NACcr, significantly reduced the responses on the active lever (from 40-50 to approximately 20 responses). These results indicate that activation of dopamine receptors in the NACsh, VP or mPFC, but not the NACcr, is involved in mediating the reinforcing effects of ethanol in the pVTA, suggesting that the 'alcohol reward' neuro-circuitry consist of, at least in part, activation of the dopamine projections from the pVTA to the NACsh, VP and mPFC

The reinforcing effects of ethanol within the nucleus accumbens shell involve activation of local GABA and serotonin receptors

Ethanol is reinforcing within the nucleus accumbens shell (NACsh), but the underlying mechanisms remain unclear. Ethanol can potentiate the function of the GABAA, GABAB, and serotonin-3 (5-HT3) receptors. Therefore, the current study tested the hypothesis that activation of these receptors would be involved in the reinforcing effects of ethanol in the NACsh. An intracranial self-administration (ICSA) procedure was used to assess the reinforcing effects of ethanol in the NACsh of alcohol preferring (P) rats. The ICSA consisted of seven sessions: four sessions to establish 150 mg% ethanol self-infusion into the NACsh; sessions 5 and 6 with co-infusion of ethanol plus one concentration of the GABAA antagonist bicuculline (10 or 100 µM), the GABAB antagonist SCH 50911 (50, 75 or 100 µM), or the 5-HT3 receptor antagonist zacopride (10 or 100 µM); and session 7 with 150 mg% ethanol alone. All groups self-infused ethanol into the NACsh and readily discriminated the active from inactive lever during the acquisition sessions. Co-infusion of 100 µM, but not 10 µM, bicuculline or zacopride significantly decreased active responses during sessions 5 and 6. Co-infusion of 75 µM, but not 50 or 100 µM, SCH 50911 significantly attenuated responses for ethanol. Overall, the results suggest that the reinforcing effects of ethanol in the NACsh may be modulated by activation of local GABAA, GABAB and 5-HT3 receptors

Alcohol drinking increases the dopamine-stimulating effects of ethanol and reduces D2 auto-receptor and group II metabotropic glutamate receptor function within the posterior ventral tegmental area of alcohol preferring (P) rats

Repeated local administration of ethanol (EtOH) sensitized the posterior ventral tegmental area (pVTA) to the local dopamine (DA)-stimulating effects of EtOH. Chronic alcohol drinking increased nucleus accumbens (NAC) DA transmission and pVTA glutamate transmission in alcohol-preferring (P) rats. The objectives of the present study were to determine the effects of chronic alcohol drinking by P rats on the (a) sensitivity and response of the pVTA DA neurons to the DA-stimulating actions of EtOH, and (b) negative feedback control of DA (via D2 auto-receptors) and glutamate (via group II mGlu auto-receptors) release in the pVTA. EtOH (50 or 150 mg%) or the D2/3 receptor antagonist sulpiride (100 or 200 μM) was microinjected into the pVTA while DA was sampled with microdialysis in the NAC shell (NACsh). The mGluR2/3 antagonist LY341495 (1 or 10 μM) was perfused through the pVTA via reverse microdialysis and local extracellular glutamate and DA levels were measured. EtOH produced a more robust increase of NACsh DA in the ‘EtOH’ than ‘Water’ groups (e.g., 150 mg% EtOH: to ~ 210 vs 150% of baseline). In contrast, sulpiride increased DA release in the NACsh more in the ‘Water’ than ‘EtOH’ groups (e.g., 200 μM sulpiride: to ~ 190–240 vs 150–160% of baseline). LY341495 (at 10 μM) increased extracellular glutamate and DA levels in the ‘Water’ (to ~ 150–180% and 180–230% of baseline, respectively) but not the ‘EtOH’ groups. These results indicate that alcohol drinking enhanced the DA-stimulating effects of EtOH, and attenuated the functional activities of D2 auto-receptors and group II mGluRs within the pVTA

The Role of Socioeconomic Status in Longitudinal Trends of Cholera in Matlab, Bangladesh, 1993-2007

There has been little evidence of a decline in the global burden of cholera in recent years as the number of cholera cases reported to WHO continues to rise. Cholera remains a global threat to public health and a key indicator of lack of socioeconomic development. Overall socioeconomic development is the ultimate solution for control of cholera as evidenced in developed countries. However, most research has focused on cross-county comparisons so that the role of individual- or small area-level socioeconomic status (SES) in cholera dynamics has not been carefully studied. Reported cases of cholera in Matlab, Bangladesh have fluctuated greatly over time and epidemic outbreaks of cholera continue, most recently with the introduction of a new serotype into the region. The wealth of longitudinal data on the population of Matlab provides a unique opportunity to explore the impact of socioeconomic status and other demographic characteristics on the long-term temporal dynamics of cholera in the region. In this population-based study we examine which factors impact the initial number of cholera cases in a bari at the beginning of the 0139 epidemic and the factors impacting the number of cases over time. Cholera data were derived from the ICDDR,B health records and linked to socioeconomic and geographic data collected as part of the Matlab Health and Demographic Surveillance System. Longitudinal zero-inflated Poisson (ZIP) multilevel regression models are used to examine the impact of environmental and socio-demographic factors on cholera counts across baris. Results indicate that baris with a high socioeconomic status had lower initial rates of cholera at the beginning of the 0139 epidemic (γ01 = -0.147, p = 0.041) and a higher probability of reporting no cholera cases (α01 = 0.156, p = 0.061). Populations in baris characterized by low SES are more likely to experience higher cholera morbidity at the beginning of an epidemic than populations in high SES baris

Under-representation of males in the early years: the challenges leaders face

This article investigates why there appears to be an under-representation of males in comparison to their female colleagues in the Early Years (EY) sector, and the perception of male teachers progressing more quickly to leadership positions when they do enter this context. Using case studies of final year male students on an Initial Teacher Training (ITT) undergraduate degree course at one university, we attempt to analyse data on male under-representation in Early Years against contemporary theories of identity, power and leadership. Questionnaires and interviews were conducted with the male sample group and male senior leaders in primary schools to gain an overview as to the leadership support they needed and provided. Our tentative findings suggested that male trainees are happy to work in an Early Years context and take leadership positions, but the challenge for leaders is that male trainees require strong leadership mentoring processes to help overcome perceived contextual barriers

The Neural Time Course of Semantic Ambiguity Resolution in Speech Comprehension.

Semantically ambiguous words challenge speech comprehension, particularly when listeners must select a less frequent (subordinate) meaning at disambiguation. Using combined magnetoencephalography (MEG) and EEG, we measured neural responses associated with distinct cognitive operations during semantic ambiguity resolution in spoken sentences: (i) initial activation and selection of meanings in response to an ambiguous word and (ii) sentence reinterpretation in response to subsequent disambiguation to a subordinate meaning. Ambiguous words elicited an increased neural response approximately 400-800 msec after their acoustic offset compared with unambiguous control words in left frontotemporal MEG sensors, corresponding to sources in bilateral frontotemporal brain regions. This response may reflect increased demands on processes by which multiple alternative meanings are activated and maintained until later selection. Disambiguating words heard after an ambiguous word were associated with marginally increased neural activity over bilateral temporal MEG sensors and a central cluster of EEG electrodes, which localized to similar bilateral frontal and left temporal regions. This later neural response may reflect effortful semantic integration or elicitation of prediction errors that guide reinterpretation of previously selected word meanings. Across participants, the amplitude of the ambiguity response showed a marginal positive correlation with comprehension scores, suggesting that sentence comprehension benefits from additional processing around the time of an ambiguous word. Better comprehenders may have increased availability of subordinate meanings, perhaps due to higher quality lexical representations and reflected in a positive correlation between vocabulary size and comprehension success