Pughneville7898

Heavy alcohol consumption followed by periods of abstinence (i.e., binge drinking) during adolescence is a concern for both acute and chronic health issues. Persistent brain damage after adolescent intermittent ethanol exposure in rodents, a model of binge drinking, includes reduced hippocampal neurogenesis and a loss of neurons in the basal forebrain that express the cholinergic phenotype. The circuit formed between those regions, the septohippocampal pathway, is critical for learning and memory. Furthermore, this circuit is also altered during the aging process. Thus, we examined whether pathology in septohippocampal circuit and impairments in spatial behaviors are amplified during aging following adolescent intermittent ethanol exposure. Female and male rats were exposed to intermittent intragastric gavage of water (control) or 20% ethanol (dose of 5 g/kg) for a 2 days on/off cycle from postnatal days 25-55. Either 2 (young adult) or 12-14 (middle-age) months post exposure, rats were tested on two spatial egardless of sex, are impaired at determining discrete spatial relationship between objects. This type of pattern separation impairment was associated with a loss of neurogenesis. Thus, binge-type adolescent ethanol exposure does affect the septohippocampal circuit, and can accelerate age-related cognitive impairment on select spatial tasks.Tobacco use disorder continues to be a leading public health issue and cause of premature death in the United States. Nicotine is considered as the major tobacco alkaloid causing addiction through its actions on nicotinic acetylcholine receptors (nAChRs). Current pharmacotherapies targeting nicotine's effects produce only modest effectiveness in promoting cessation, highlighting the critical need for a better understanding of mechanisms of nicotine addiction to inform future treatments. There is growing interest in identifying potential contributions of non-nicotine components to tobacco reinforcement. Cotinine is a minor alkaloid, but the major metabolite of nicotine that can act as a weak agonist of nAChRs. Accumulating evidence indicates that cotinine produces diverse effects and may contribute to effects of nicotine. In this review, we summarize findings implicating cotinine as a neuroactive metabolite of nicotine and discuss available evidence regarding potential mechanisms underlying its effects. Preclinical findings reveal that cotinine crosses the blood brain barrier and interacts with both nAChRs and non-nAChRs in the nervous system, and produces neuropharmacological and behavioral effects. Clinical studies suggest that cotinine is psychoactive in humans. However, reviewing evidence regarding mechanisms underlying effects of cotinine provides a mixed picture with a lack of consensus. Therefore, more research is warranted in order to provide better insight into the actions of cotinine and its contribution to tobacco addiction.Laboratory workflows and preclinical models have become increasingly diverse and complex. Confronted with the dilemma of a multitude of information with ambiguous relevance for their specific experiments, scientists run the risk of overlooking critical factors that can influence the planning, conduct and results of studies and that should have been considered a priori. To address this problem, we developed "PEERS" (Platform for the Exchange of Experimental Research Standards), an open-access online platform that is built to aid scientists in determining which experimental factors and variables are most likely to affect the outcome of a specific test, model or assay and therefore ought to be considered during the design, execution and reporting stages. The PEERS database is categorized into in vivo and in vitro experiments and provides lists of factors derived from scientific literature that have been deemed critical for experimentation. The platform is based on a structured and transparent system for rating twhich to judge the quality of information available on a certain test or model, identifies knowledge gaps and provides guidance on the key methodological considerations that should be prioritized to ensure that preclinical research is conducted to the highest standards and best practice.Zona incerta (ZI), a largely inhibitory subthalamic region connected with many brain areas, has been suggested to serve as an integrative node for modulation of behaviors and physiological states, such as fear memory conditioning and aversion responses. It is, however, unclear whether ZI regulated the repeated social defeat stress (RSDS)-induced social conditioned place aversion (CPA) and post-traumatic stress disorder (PTSD)-like behaviors. In this study, the function of ZI was silenced via bilateral injection of tetanus toxin light chain (Tet-tox), a neurotoxin that completely blocks the evoked synaptic transmissions, expressing adeno-associated viruses (AAVs). Selleck AZD9291 We found ZI silencing (1) significantly blocked the expression of RSDS-induced social CPA with no effect on the innate preference; (2) significantly enhanced the anxiety level in mice experienced RSDS with no effect on the locomotion activity; (3) altered the PTSD-associated behaviors, including the promotion of spatial cognitive impairment and the preventions of PPI deficit and social avoidance behavior. These effects were not observed on non-stressed mice. In summary, our results suggest the important role of ZI in modulating RSDS-induced social CPA and PTSD-like behaviors.In humans, stimuli associated with alcohol availability can provoke relapse during abstinence. In this study, we investigated the role of discriminative stimuli (DS) in the control of alcohol seeking in two types of behavioral tests. The first test examined the ability of an alcohol-associated DS to promote alcohol seeking (relapse) after punishment-imposed abstinence in the presence of a different DS. Following this, we tested whether the differentially associated DS can promote and suppress alcohol self-administration in a within-session discrimination task. During the within-session discrimination task, we also tested the rate of alcohol self-administration when two DS are presented in a compound. We first trained Long-Evans male rats (n = 24) to self-administer alcohol in the presence of one DS (reward-associated discriminative stimulus, rewDS) and then punished that behavior in the presence of a different DS (punishment-associated discriminative stimulus, punDS). On the test, we found that rats tested winishment-imposed abstinence. We also implemented a within-session discrimination task that allows for the study of alcohol seeking under motivational conflict, which may be relevant for alcohol use despite negative consequences. The results from the Fos data suggest that higher alcohol seeking in approach-avoidance motivational conflict is associated with activation of sub-cortical regions but not cortical regions.Since the work of Semon was rediscovered by Schacter in 1978, there has been a renewed interest is searching for the "engram" as the locus of memory in the brain and Hebb's cell assembly has been equated with Semon's engram. There have been many theories of memory involving some concept of synaptic change, culminating in the "Hebb Synapse" theory in 1949. However, Hebb said that the idea that any two cells or systems of cells that are repeatedly active at the same time will tend to become "associated," was not his idea, but an old one. In this manuscript we give an overview of some of the theories of the neural basis of learning and memory before Hebb and describe the synaptic theory of William McDougall, which appears to have been an idea ahead of its time; so far ahead of its time that it was completely ignored by his contemporaries. We conclude by examining some critiques of McDougall's theory of inhibition and with a short discussion on the fate of neuroscientists whose ideas were neglected when first presented but were accepted as important many decades later.While a bidirectional positive link between palatable food intake and alcohol drinking has been suggested, several rodents studies report reduced alcohol drinking following palatable diets exposure. These studies utilized purified rodents' diets high in sugar/fat; however, the effects of hyper-palatable food (HPF) rich in fat and sugar on alcohol drinking remain unclear. Furthermore, neural substrates involved in HPF-mediated changes in alcohol consumption are poorly understood. Therefore, the present study evaluated the effects of patterned feeding of a hyper-palatable food (Oreo cookies) on alcohol drinking as well as dopamine (DA) and serotonin (5-HT) content in rat's mesocorticolimbic (medial-prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens) circuitry. Male Long Evans rats received 8-weeks of intermittent (Mon, Tue, Wed) Oreo cookies access, which induced a patterned feeding, in which rats in the Oreo group overconsumed calories on HPF days whereas underconsumption was observed on chow only (Thu, Fri) days. Following HPF exposure, alcohol consumption was evaluated while patterned feeding continued. Alcohol intake in the Oreo group was significantly lower as compared to the chow controls. However, alcohol intake in the Oreo group increased to the levels seen in the group receiving chow following the suspension of patterned HPF feeding. Finally, DA levels in the nucleus accumbens were significantly greater, whereas its metabolite (DOPAC) levels were lower in the Oreo group compared to the chow controls. Surprisingly, 5-HT levels remained unaltered in all tested brain areas. Together, these data suggest that HPF-associated increased DA availability and reduced DA turnover within mesocorticolimbic circuitry may regulate alcohol drinking following patterned HPF feeding.Appropriate social behavior in aggressive-provocative interactions is a prerequisite for a peaceful life. In previous research, the dysfunctions of the control of aggression were suggested to be modulated by enhanced bottom-up (sub-cortically driven) and reduced top-down (iso-cortical frontal) processing capability. In the present study, two groups of individuals with enhanced (EG) and normal (NG) experiences of violent acts during their socialization made binary behavioral decisions in quasi-realistic social interactions. These interactions were presented in short video clips taken from a first-person perspective. The video clips showed social interaction scenarios oriented on realistic everyday life situations. The behavioral data supported the distinct affective qualities of three categories of social interactions. These categories were labeled as aggressive-provocative, social-positive, and neutral-social interactions. Functional neuroimaging data showed extended activation patterns and higher signal inte or strengthening the association between prototypical social contexts (e.g., aggressive-provocative interactions) and appropriate behaviors as a response to it provides a promising approach to successfully re-socialize people with a delinquent history.The medial temporal lobe (MTL) is crucial for memory encoding and recognition. The time course of these processes is unknown. The present study juxtaposed encoding and recognition in a single paradigm. Twenty healthy subjects performed a continuous recognition task as brain activity was monitored with a high-density electroencephalography. The task presented New pictures thought to evoke encoding. The stimuli were then repeated up to 4 consecutive times to produce over-familiarity. These repeated stimuli served as "baseline" for comparison with the other stimuli. Stimuli later reappeared after 9-15 intervening items, presumably associated with new encoding and recognition. Encoding-related differences in evoked response potential amplitudes and in spatiotemporal analysis were observed at 145-300 ms, whereby source estimation indicated MTL and orbitofrontal activity from 145 to 205 ms. Recognition-related activity evoked by late repetitions occurred at 405-470 ms, implicating the MTL and neocortical structures.