The present article provides a narrative review on how language communicates sensory information and how knowledge of sight and sound develops in individuals born deaf or blind. Studying knowledge of ...the perceptually inaccessible sensory domain for these populations offers a lens into how humans learn about that which they cannot perceive. We first review the linguistic strategies within language that communicate sensory information. Highlighting the power of language to shape knowledge, we next review the detailed knowledge of sensory information by individuals with congenital sensory impairments, limitations therein, and neural representations of imperceptible phenomena. We suggest that the acquisition of sensory knowledge is supported by language, experience with multiple perceptual domains, and cognitive and social abilities which mature over the first years of life, both in individuals with and without sensory impairment. We conclude by proposing a developmental trajectory for acquiring sensory knowledge in the absence of sensory perception.
•Linguistic structure and dedicated sensory language communicate sensory information.•Deaf and blind individuals develop rich knowledge of sound and sight.•Linguistic mechanisms for acquiring sensory knowledge are universal.•Sensory impairment may increase reliance on linguistic structure in language learning.•A proposal for language learning in blind and deaf children is articulated.
The last decade has seen major advances in neuroscience tools allowing us to selectively modulate cellular pathways in freely moving animals. Chemogenetic approaches such as designer receptors ...exclusively activated by designer drugs (DREADDs) permit the remote control of neuronal function by systemic drug administration. These approaches have dramatically advanced our understanding of the neural control of behaviour. Here, we review the different techniques and genetic approaches available for the restriction of chemogenetic receptors to defined neuronal populations. We highlight the use of a dual virus approach to target specific circuitries and the effectiveness of different routes of administration of designer drugs. Finally, we discuss the potential caveats associated with DREADDs including off‐target effects of designer drugs, the effects of chronic chemogenetic receptor activation and the issue of collateral projections associated with DREADD activation and inhibition.
New steps for treating alcohol use disorder Campbell, Erin J.; Lawrence, Andrew J.; Perry, Christina J.
Psychopharmacology,
06/2018, Letnik:
235, Številka:
6
Journal Article
Recenzirano
Alcohol use disorder is a complex syndrome with multiple treatment points including drug-induced pathology, withdrawal management, behavioral/cognitive strategies, and relapse prevention. These ...different components may be complicated by genotype and phenotype. A huge milestone for the treatment of alcohol use disorder across several countries in the last 10 years was the introduction of practice guidelines integrating clinical expertise and research evidence. These provide a summary of interventions that have been shown to be effective following rigorous and replicated clinical trials. Inspection of these guidelines reveals good consistency, but little evidence of progress in treatment approaches for alcohol use disorder over the past decade. In this mini-review, we discuss emerging treatments for alcohol use disorder that may supplement or improve the evidence-based treatments that are currently recommended. New medications, the emergence of digital technology, and other novel approaches such as transcranial magnetic stimulation are all discussed with reference to treatments already in practice. We also consider how individual differences in genotype and phenotype may affect outcomes. Together with improvements in technology, this knowledge offers a powerful tool for designing personalized approaches to treatment, and hence improving prognosis for rehabilitation programs.
Individual variations in animal behaviour can be used to describe relationships between different constructs, as well as the underlying neurobiological mechanisms responsible for such variation. In ...humans, variation in the expression of certain traits contributes to the onset of psychopathologies, such as drug addiction. Addiction is characterised by persistent drug use despite negative consequences, but it occurs in only a sub-population of drug users. Compulsive drug use is modelled in laboratory animals by punishing a drug-reinforced operant response. It has been reported that there is individual variability in the response to punishment, and in this report we aim to further define the conditions under which this variation can be observed. We have previously used footshock punishment to suppress alcohol seeking in an animal model of context-induced relapse to alcohol seeking after punishment-imposed abstinence. Here we present a re-examination of the training and punishment data from a large cohort of rats (n=499) collected over several years. We found evidence for a bimodal distribution in the response to punishment in alcohol preferring P rats. We only observed this population split when rats received constant shock intensity for three sessions, but not when increasing shock intensity was used. This observation provides evidence for the existence of two distinct groups of rats, defined by their response to punishment, in an otherwise homogeneous population. The implications of this observation are discussed in reference to prior observations using punishment of other addictive drugs (cocaine and methamphetamine), the potential causes of this phenomenon, and with broader implications for the cause of alcohol and drug addiction in humans.
•Individual differences in the sensitivity to punishment are thought to model compulsive drug seeking.•We show that alcohol preferring P rats have substantial variability to punishment of alcohol-reinforced behaviour.•Punishment with constant, mild shock intensity over 3days revealed a bimodal distribution in the population.•Punishment with increasing shock intensity results in total suppression of alcohol seeking.
•Suvorexant, a dual orexin receptor antagonist, has been FDA approved for the treatment of insomnia.•Sleep disruptions occur in alcohol use disorder and sleep deprivation is a potent factor promoting ...relapse to alcohol use.•Suvorexant may address alcohol-induced sleep disruptions, which may in turn help reduce or prevent relapse.
There are currently 3 FDA approved treatments for alcohol use disorder (AUD) in the USA, opioid receptor antagonists such as naltrexone, disulfiram and acamprosate. To date, these have been largely inadequate at preventing relapse at a population level and this may be because they only target certain aspects of AUD. Recently, suvorexant, a dual orexin receptor antagonist, has been FDA approved for the treatment of insomnia. Importantly, sleep disruptions occur during both acute and prolonged alcohol exposure and sleep deprivation is a potent factor promoting relapse to alcohol use. In this mini review article, we explore the therapeutic potential of suvorexant for the treatment of AUD. In particular, we highlight that in addition to altering the motivational properties of alcohol, suvorexant may also address key physiological components associated with alcohol withdrawal and abstinence, such as sleep disruptions, which should in turn help reduce or prevent relapse.
•Orexin modulates emotional dysregulation during withdrawal from alcohol use.•We highlight the role of orexin in sleep-wake regulation and alcohol use disorder.•We discuss our plan for a trial ...examining suvorexant in comorbid insomnia and AUD.
Alcohol use disorder (AUD) is a complex neuropsychiatric disease state in which currently approved pharmacotherapeutics are of relatively low effect at a population level. One reason for this may be that current pharmacotherapeutics focus on the reward pathway in relapse prevention, rather than addressing AUD from a holistic perspective. Importantly, one often overlooked symptom of AUD is sleep disruption. In recent years, an efficient, relatively low risk and economic strategy that has proven successful in other disorders is the repositioning or repurposing of drugs approved for the treatment of other indications. Suvorexant, a dual orexin receptor antagonist, has been licensed for the treatment of insomnia in the USA, Australia and Japan. The orexin system also plays a role in the emotional dysregulation that occurs during withdrawal from alcohol use and in alcohol-seeking behaviours. These two factors prompted the planning of a clinical trial into the use of suvorexant to treat insomnia in alcohol dependent individuals during and 24 weeks post-acute alcohol withdrawal. In this review we outline the comorbid nature of AUD and sleep disruptions. We then highlight the role of the orexin system in both sleep-wake regulation and AUD. Finally, we discuss our plan for a Phase II double blind placebo controlled trial examining the effectiveness of suvorexant for the treatment of comorbid insomnia and AUD.
Traumatic events during early life have been linked with later life psychopathology. To understand this risk factor, researchers have studied the effects of prenatal and postnatal early life stress ...on neurochemical changes. Here we review the rodent literature on sex differences and sex‐specific impact of early life stress on frontal cortex neurochemistry. This region is implicated in regulating motivation and emotion, which are often disrupted in psychological disorders. The prefrontal cortex (PFC) in particular is one of the last brain regions to develop, and there are sex differences in the rate of this development. To draw direct comparisons between sexes, our review of the literature was restricted to studies where the effects of prenatal or postnatal stress had been described in male and female littermates. This literature included research describing glutamate, γ‐amino butyric acid (GABA), corticosteroids, monoamines, and cannabinoids. We found that sex‐dependent effects of stress are mediated by the age at which stress is experienced, age at test, and type of stress endured. More research is required, particularly into the effects of adolescent stress on male and female littermates. We hope that a greater understanding of sex‐specific susceptibilities in response to stress across development will help to uncover risk factors for psychological disorders in vulnerable populations.
In this narrative review, we investigated whether the effect of early‐life stress on neurochemistry of the frontal cortex was dependent on sex. Although we did find that males and females were differentially affected by stress, there were no clear patterns regarding which sex was more vulnerable. Furthermore, the impact of stress was also dependent on the timing, and the intensity, duration, and type of stress experienced. Clearly more research is required to understand the full impact of early life stress on the frontal cortex. Figure created with BioRender.com.
Maintaining abstinence and preventing relapse are key to the successful recovery from alcohol use disorder. There are two main ways individuals with alcohol use disorder abstain from alcohol use: ...forced (e.g., incarceration) and voluntary. Voluntary abstinence is often evoked due to the negative consequences associated with excessive alcohol consumption. This study investigated relapse-like behavior to alcohol seeking following acute, forced, and voluntary abstinence. Male rats had increased operant self-administration responding throughout training compared to females; however, females consumed greater amounts of alcohol in g/kg. Both male and female rats achieved voluntary abstinence, which was induced using an electric barrier on the operant chamber floor with alcohol readily available during this period. Interestingly, male rats that underwent voluntary abstinence displayed reduced alcohol seeking compared to males in the acute and forced abstinence groups. This difference in alcohol seeking behavior across abstinence groups was not observed in female rats. Quantification of neuronal activation (Fos protein) revealed numerous brain regions (e.g., ventral subiculum and lateral habenula) to be associated with the reduced reinstatement propensity seen in male rats that underwent voluntary abstinence. Additionally, hierarchical clustering found enhanced functional connectivity and coordination in the male voluntary abstinence group compared to the male forced abstinence group. Collectively, these data implicate a sexual dimorphism in the effect that voluntary abstinence, at least in the model employed here, has on relapse-like behavior. This maybe driven by reduced neuronal activation at a network level and enhanced functional connectivity and integration.
Corticotropin releasing factor (CRF) is a key component of stress responsivity, modulating related behaviors including anxiety and reward. Difficulties identifying CRF neurons, using traditional ...approaches including immunohistochemistry, has led to the development of a number of transgenic CRF reporter mice. The Crh-IRES-Cre::Ai14 (tdTomato) reporter mouse is increasing in popularity as a useful tool to assess the localization, connectivity and function of CRF neurons in various stress-related behaviors. However, without proper characterization of reporter expression, the in vivo and in vitro manifestations resulting from the manipulation of these cells must be interpreted with caution. Here we mapped the distribution of tdTomato-expressing CRF cells throughout the rostro-caudal extent of the Crh-IRES-Cre::Ai14 mouse brain. To determine if reporter expression faithfully reproduced native CRF expression, we assessed the colocalization of CRF expression with tdTomato reporter expression across several brain regions. Good concordance was observed in the extended amygdala and paraventricular nucleus of the hypothalamus (PVN), while discrepancies were observed within the lateral hypothalamus and hippocampus. Finally, we examined the activation of CRF neurons in Crh-IRES-Cre::Ai14 mice in response to different types of stressors using Fos immunohistochemistry. Acute psychological (swim) and pharmacological (yohimbine) stress stimulated Fos-protein expression in PVN CRF neurons. Interestingly though, exposure to four daily restraint stress sessions followed by a novel acute stressor did not further recruit CRF neurons across any brain region examined. Our results highlight the importance of thoroughly characterizing reporter mice before use and suggest that acute versus repeated stress may differentially impact the CRF system.
This article is part of the Special Issue entitled ‘Hypothalamic Control of Homeostasis’.
•The Crh-IRES-Cre::Ai14 mouse had faithful reporter expression in BNST and PVN.•The Crh-IRES-Cre::Ai14 mouse had unfaithful reporter expression in PVT and LH.•Acute stress stimulated Fos expression in PVN CRF neurons.•Chronic stress followed by a novel acute stressor did not recruit CRF neurons.
Traffic-related air pollution (TRAP) poses a significant public health risk that is associated with adverse birth outcomes. Large roadway infrastructure projects present a natural experiment to ...examine how resulting congestion change is associated with adverse birth outcomes for nearby populations. This study is designed to examine the influence of living close to a roadway before, during, and after a construction project using a difference-in-differences design. We integrated data on all large roadway construction projects (defined as widening of existing roads, building new roads, improving bridges, installing intelligent transportation systems, improving intersections, and installing or upgrading traffic signals) in Texas from 2007 to 2016 with Vital Statistic data for all births with residential addresses within 1 km of construction projects. Our outcomes included term low birth weight, term birth weight, preterm birth, and very preterm birth. Using a difference-in-differences design, we included births within 3 years of construction start and 2 years of construction end. In our main model, the exposed group is limited to pregnant individuals residing within 300 m of a construction project, and the control group includes those living within 300–1000 m from a project. We used regression models to estimate the influence of construction on infant health. We included 1,360 large roadway construction projects linked to 408,979 births. During construction, we found that the odds of term low birth weight increased by 19% (95% CI: 1.05, 1.36). However, we saw little evidence of an association for other birth outcomes. Contrary to our hypothesis of decreased TRAP after construction ends, we did not observe consistent improvements post-construction for pregnant individuals living within 300 m. Continued consideration of the influence of traffic congestion programs on birth outcomes is necessary to inform future policy decisions.
•Effect of road construction on birth outcomes near roads vs further away.•Increased odds of term low birth weight within 300 m of ongoing construction projects.•No improvement in infant health outcomes after road construction projects.•Need for further research on infrastructure projects and local health outcomes.
PDF
