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The actuation of micro- and nanostructures controlled by external stimuli remains one of the exciting challenges in nanotechnology due to the wealth of fundamental questions and potential applications in energy harvesting, robotics, sensing, biomedicine, and tunable metamaterials. Photoactuation utilizes the conversion of light into motion through reversible chemical and physical processes and enables remote and spatiotemporal control of the actuation. Here, we report a fast light-to-motion conversion in few-nanometer thick bare polydopamine (PDA) membranes stimulated by visible light. Light-induced heating of PDA leads to desorption of water molecules and contraction of membranes in less than 140 μs. Switching off the light leads to a spontaneous expansion in less than 20 ms due to heat dissipation and water adsorption. Our findings demonstrate that pristine PDA membranes are multiresponsive materials that can be harnessed as robust building blocks for soft, micro-, and nanoscale actuators stimulated by light, temperature, and moisture level.

A consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly into the mesolimbic dopamine system, alterations in dendritic spine and gene expression within the nucleus accumbens shell (AcbSh), and if treatment with the HDACII inhibitor TSA could normalize the consequences of AIE. Rats were exposed to the AIE (4 g/kg ig; 3 days a week) or water (CON) during adolescence, and all testing occurred during adulthood. CON and AIE rats were microinjected with EtOH directly into the posterior VTA and dopamine and glutamate levels were recorded in the AcbSh. Separate groups of AIE and CON rats were sacrificed during adulthood and Taqman arrays and dendritic spine morphology assessments were performed. The data indicated that exposure to AIE resulted in a significant leftward and upward shift in the dose-response curve for an increase in dopamine in the AcbSh following EtOH microinjection into the posterior VTA. Taqman array indicated that AIE exposure affected the expression of target genes (Chrna7, Impact, Chrna5). The data indicated no alterations in dendritic spine morphology in the AcbSh or any alteration in AIE effects by TSA administration. Binge-like EtOH exposure during adolescence enhances the response to acute ethanol challenge in adulthood, demonstrating that AIE produces a hyperdopaminergic mesolimbic system in both male and female Wistar rats. The neuroadaptations induced by AIE in the AcbSh could be part of the biological basis of the observed negative consequences of adolescent binge-like alcohol exposure on adult drug self-administration behaviors.

The ability of drugs of abuse to increase mesolimbic levels of dopamine is a characteristic associated with their rewarding effects. Exactly how these effects are produced by different substances is not as well characterised. Our previous work in rats has demonstrated that accumbal glycine receptors (GlyRs) are involved in mediating the dopamine-activating effects of ethanol, and in modulating ethanol intake. In this study the investigation of GlyR involvement was extended to include several different drugs of abuse. By using microdialysis and electrophysiology we compared effects of addictive drugs, with and without the GlyR antagonist strychnine, on dopamine levels and neurotransmission in nucleus accumbens. The dopamine-increasing effect of systemic ethanol and the drug-induced change in neurotransmission in vitro, as measured by microdialysis and field potential recordings, were dependent on GlyRs in nAc. Accumbal GlyRs were also involved in the actions of tetrahydrocannabinol and nicotine, but not in those of cocaine or morphine. These data indicate that accumbal GlyRs play a key role in ethanol-induced dopamine activation and contribute also to that of cannabinoids and nicotine.

Bipolar disorder co-occurs with alcohol use disorder at a rate 3-5 times higher than the general population. We recently reported that individuals with bipolar disorder differ in the positive stimulating and anxiolytic effects of alcohol compared with healthy peers. This study used a randomized, placebo-controlled, cross-over, within-subject alcohol administration design to investigate neurobiological mechanisms within ventral prefrontal cortical (vPFC) systems that may underlie altered sensitivity to alcohol in bipolar disorder (NCT04063384). Forty-seven young adults (n = 23 with bipolar disorder, 64% women) completed clinical assessment and two beverage administration sessions (alcohol and placebo, counter-balanced). Participants were dosed to 0.08 g% breath alcohol concentration during the alcohol condition and completed measures of subjective response to alcohol and an emotional processing fMRI task during the ascending limb. Timing during the placebo condition mirrored the alcohol session. Acute alcohol was associated with reduced functional connectivity between the insula - subcallosal cingulate cortex, and increased connectivity between the left nucleus accumbens - ventromedial PFC in bipolar disorder, but with no change in functional connectivity between these regions in healthy peers. Alcohol-related increases in nucleus accumbens - ventromedial PFC functional connectivity was associated with greater positive stimulating effects of alcohol in bipolar disorder and heavier recent alcohol use. Results suggest vPFC brain systems respond differently to acute alcohol during emotional processing in young adults with bipolar disorder compared with healthy peers, and that vPFC system responses relate to the subjective experience of intoxication and recent alcohol use.

Abstract Ethanol-induced sleep time was measured in mice after administration of L-3,4-dihydroxyphenylalanine (L-DOPA), L-tryptophan (L-TP), DL-5-hydroxytryptophan (5-HTP), serotonin (5HT), DL-5-hydroxyindole-3-acetic acid (5HIAA), and DL-parachlorophenylalanine (pCPA), a serotonin depletor. The pCPA administration, with concomitant reduction of brain serotonin, had no effect on ethanol-induced sleep; TP, 5-HTP and 5HIAA failed also to significantly enhance ethanol sleep in mice. However, serotonin significantly enhanced sleeping time of mice administered an ineffective dose of ethanol. Pretreatment with L-DOPA produced a marked prolongation of ethanol narcosis with a concomitant large increase in whole brain dopamine (DA). Administration of L-DOPA and pCPA, together, produced a smaller augmentation of ethanol effects.

Our presently somewhat limited knowledge of the modulation of the content, release and turnover of endorphins in brain and pituitary by acute and chronic drug treatment is reviewed and discussed particularly in relation to the problem of addiction. In vitro studies in striatal slices and isolated anterior and intermediate/posterior lobes of the pituitary point to the existence of specific interactions between endorphins and neurotransmitters. In vivo studies have revealed acute GABA-mediated effects of benzodiazepines upon striatal levels of met-enkephalin activity. Morphine exerts no acute effects upon endorphin levels, but decreases the levels of particular endorphins in specific areas of brain and pituitary after long-term treatment; somewhat similar effects are observed after prolonged intake of ethanol, whereas chronic haloperidol treatment results in an increase in levels of endorphins in brain and pituitary. Incorporation studies employing the intermediate/posterior lobe of the pituitary have revealed that the changes in beta-endorphin levels produced by prolonged treatment with morphine or haloperidol reflect a respective depressed or enhanced synthesis of the beta-endorphin precursor pro-opiocortin, whilst the enzymatic processing of this precursor remains unmodified. Studies in cell-free preparations demonstrated that m-RNA extracted from the intermediate/posterior lobes of chronically morphinized rats possesses a decreased "activity".

High ethanol intake is well known to induce both anxiolytic and anxiogenic effects, in correlation with chromatin remodeling in the amygdaloid brain region and deficits in cell proliferation and survival in the hippocampus of rodents. Whether only moderate but chronic ethanol intake in C57BL/6J mice could also have an impact on chromatin remodeling and neuroplasticity was addressed here. Chronic ethanol consumption in a free choice paradigm was found to induce marked changes in the expression of genes implicated in neural development and histone post-translational modifications in the mouse hippocampus. Transcripts encoding neural bHLH activators and those from Bdnf exons II, III and VI were upregulated, whereas those from Bdnf exon VIII and Hdacs were downregulated by ethanol compared with water consumption. These ethanol-induced changes were associated with enrichment in both acetylated H3 at Bdnf promoter PVI and trimethylated H3 at PII and PIII. Conversely, acetylated H3 at PIII and PVIII and trimethylated H3 at PVIII were decreased in ethanol-exposed mice. In parallel, hippocampal brain-derived neurotrophic factor (BDNF) levels and TrkB-mediated neurogenesis in the dentate gyrus were significantly enhanced by ethanol consumption. These results suggest that, in C57BL/6J mice, chronic and moderate ethanol intake produces marked epigenetic changes underlying BDNF overexpression and downstream hippocampal neurogenesis.

Purpose: Heavy ion and proton brain irradiations occur during space travel and in Hadron therapy for cancer. Heavy ions produce distinct patterns of energy deposition in neuron cells and brain tissues compared to X-rays leading to large uncertainties in risk estimates. We make a critical review of findings from research studies over the last 25 years for understanding risks at low dose. Conclusions: A large number of mouse and rat cognitive testing measures have been reported for a variety of particle species and energies for acute doses. However, tissue reactions occur above dose thresholds and very few studies were performed at the heavy ion doses to be encountered on space missions (<0.04 Gy/y) or considered dose-rate effects, such that threshold doses are not known in rodent models. Investigations of possible mechanisms for cognitive changes have been limited by experimental design with largely group specific and not subject specific findings reported. Persistent oxidative stress and activated microglia cells are common mechanisms studied, while impairment of neurogenesis, detriments in neuron morphology, and changes to gene and protein expression were each found to be important in specific studies. Future research should focus on estimating threshold doses carried out with experimental designs aimed at understating causative mechanisms, which will be essential for extrapolating rodent findings to humans and chronic radiation scenarios, while establishing if mitigation are needed.

Human genetic variation in the nicotinic receptor gene cluster CHRNA5/A3/B4, in particular the non-synonymous and frequent CHRNA5 variant rs16969968 (α5SNP), has an important consequence on smoking behavior in humans. A number of genetic association studies have additionally implicated the CHRNA5 gene in addictions to other drugs, and also body mass index (BMI). Here, we model the α5SNP, in a transgenic rat line, and establish its role in alcohol dependence, and feeding behavior. Rats expressing the α5SNP consume more alcohol, and exhibit increased relapse to alcohol seeking after abstinence. This high-relapsing phenotype is reflected in altered activity in the insula, linked to interoception, as established using c-Fos immunostaining. Similarly, relapse to food seeking is increased in the transgenic group, while a nicotine treatment reduces relapse in both transgenic and control rats. These findings point to a general role of this human polymorphism in reward processing, and multiple addictions other than smoking. This could pave the way for the use of medication targeting the nicotinic receptor in the treatment of alcohol use and eating disorders, and comorbid conditions in smokers.