scholarly journals Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats

2019 ◽  
Author(s):  
Yayi Swain ◽  
Peter Muelken ◽  
Annika Skansberg ◽  
Danielle Lanzdorf ◽  
Zachary Haave ◽  
...  
Keyword(s):  
Individual Differences ◽  
Drug Exposure ◽  
Opioid Addiction ◽  
Self Administration ◽  
Behavioral Measures ◽  
Acute Dependence ◽  
Individual Measure ◽  
Spontaneous Withdrawal ◽  
Relationship Of ◽  
Initial Drug

AbstractUnderstanding factors contributing to individual differences in vulnerability to opioid addiction is essential for developing more effective preventions and treatments, yet few reliable behavioral predictors of subsequent opioid self-administration have been identified in rodents. Sensitivity to the acute effects of initial drug exposure predicts later addiction vulnerability in both humans and animals, but the relationship of sensitivity to withdrawal from initial drug exposure and later drug use vulnerability is unclear. The goal of the current study was to evaluate whether the degree of anhedonia experienced during withdrawal from early opioid exposure predicts subsequent vulnerability to opioid addiction. Rats were first tested for withdrawal sensitivity following acute injections of morphine (i.e., “acute dependence”), measured as elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during naloxone-precipitated and spontaneous withdrawal. Rats were then tested for addiction vulnerability using various measures of i.v. morphine self-administration (MSA) including acquisition, demand, extinction, and reinstatement induced by morphine, stress, and/or drug-associated cues. Greater naloxone-precipitated withdrawal across repeated morphine injections and greater peak spontaneous withdrawal severity following a single morphine injection were associated with lower addiction vulnerability on multiple MSA measures. Withdrawal-induced anhedonia predicted a wider range of MSA measures than did any individual measure of MSA itself. These data suggest that high anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid addiction vulnerability in rodents, thereby establishing one of the first behavioral measures to predict individual differences in opioid SA. This model promises to be useful for furthering our understanding of behavioral and neurobiological mechanisms underlying vulnerability to opioid addiction.

scholarly journals Are the Acute Effects of THC Different in Aging Adults?

2021 ◽  
Vol 11 (5) ◽  
pp. 590
Author(s):  
Raeghan L. Mueller ◽  
Jarrod M. Ellingson ◽  
L. Cinnamon Bidwell ◽  
Angela D. Bryan ◽  
Kent E. Hutchison
Keyword(s):  
Older Adults ◽  
Young Adults ◽  
Age Groups ◽  
Young Group ◽  
Self Administration ◽  
Behavioral Measures ◽  
Younger Adults ◽  
Different Types ◽  
Before And After ◽  
Aging Adults

In recent years of expanding legalization, older adults have reported the largest increase in cannabis use of any age group. While its use has been studied extensively in young adults, little is known about the effects of THC in older adults and whether the risks of cannabis might be different, particularly concerning intoxication and cognition. The current study investigated whether age is associated with the deleterious effects of THC on cognitive performance and other behavioral measures before and after ad libitum self-administration of three different types of cannabis flower (THC dominant, THC + CBD, and CBD dominant). Age groups consisted of young adults (ages 21–25) and older adults (ages 55–70). Controlling for pre-use scores on all measures, the THC dominant chemovar produced a greater deleterious effect in younger adults compared with older adults in tests of learning and processing speed, whereas there were no differences between old and young in the effects of the other chemovars. In addition, the young group reported greater cannabis craving than the older group after using the THC chemovar. Consistent with some reports in the preclinical literature, the findings suggest that older adults may be less sensitive to the effects of THC on cognitive and affective measures.

scholarly journals Dispositional individual differences in cognitive effort investment: establishing the core construct

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Corinna Kührt ◽  
Sebastian Pannasch ◽  
Stefan J. Kiebel ◽  
Alexander Strobel
Keyword(s):  
Individual Differences ◽  
Latent Variables ◽  
Effortful Control ◽  
Factor Model ◽  
Cognitive Effort ◽  
Self Control ◽  
Behavioral Measures ◽  
Effort Discounting ◽  
Cognitive Motivation ◽  
Goal Directed Behavior

Abstract Background Individuals tend to avoid effortful tasks, regardless of whether they are physical or mental in nature. Recent experimental evidence is suggestive of individual differences in the dispositional willingness to invest cognitive effort in goal-directed behavior. The traits need for cognition (NFC) and self-control are related to behavioral measures of cognitive effort discounting and demand avoidance, respectively. Given that these traits are only moderately related, the question arises whether they reflect a common core factor underlying cognitive effort investment. If so, the common core of both traits might be related to behavioral measures of effort discounting in a more systematic fashion. To address this question, we aimed at specifying a core construct of cognitive effort investment that reflects dispositional differences in the willingness and tendency to exert effortful control. Methods We conducted two studies (N = 613 and N = 244) with questionnaires related to cognitive motivation and effort investment including assessment of NFC, intellect, self-control and effortful control. We first calculated Pearson correlations followed by two mediation models regarding intellect and its separate aspects, seek and conquer, as mediators. Next, we performed a confirmatory factor analysis of a hierarchical model of cognitive effort investment as second-order latent variable. First-order latent variables were cognitive motivation reflecting NFC and intellect, and effortful self-control reflecting self-control and effortful control. Finally, we calculated Pearson correlations between factor scores of the latent variables and general self-efficacy as well as traits of the Five Factor Model of Personality for validation purposes. Results Our findings support the hypothesized correlations between the assessed traits, where the relationship of NFC and self-control is specifically mediated via goal-directedness. We established and replicated a hierarchical factor model of cognitive motivation and effortful self-control that explains the shared variance of the first-order factors by a second-order factor of cognitive effort investment. Conclusions Taken together, our results integrate disparate literatures on cognitive motivation and self-control and provide a basis for further experimental research on the role of dispositional individual differences in goal-directed behavior and cost–benefit-models.

scholarly journals Candida albicans exhibits distinct cytoprotective responses to anti-fungal drugs that facilitate the evolution of drug resistance

2020 ◽  
Author(s):  
V Bettauer ◽  
S Massahi ◽  
S Khurdia ◽  
ACBP Costa ◽  
RP Omran ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Drug Exposure ◽  
Fluorescent Imaging ◽  
Late Time ◽  
Transport Mechanisms ◽  
Short Term ◽  
Anti Fungal ◽  
Initial Drug

AbstractWe developed a modified protocol for nanolitre droplet-based single cell sequencing appropriate for fungal settings, and used it to transcriptionally profiled several thousands cells from a prototrophic Candida albicans population and several drug exposed colonies (incl. fluconazole, caspofungin and nystatin). Thousands of cells from each colony were profiled both at early and late time points post-treatment in order to infer survival trajectories from initial drug tolerance to drug resistance. We find that prototrophic C. albicans populations differentially and stochastically express cytoprotective epigenetic programs. For all drugs, there is evidence that tolerant individuals partition into distinct subpopulations, each with a unique survival strategy involving different regulatory programs. These responses are weakly related to changes in morphology (shift from white to opaque forms, or shift from yeast to filamentous forms). In turn, those subpopulations that successfully reach resistance each have a distinct multivariate epigenetic response that coordinates the expression of efflux pumps, chaperones, transport mechanisms, and cell wall maintenance. Live cell fluorescent imaging was used to validate predictions of which molecular responses most often led to survival after drug exposure. Together our findings provide evidence that C. albicans has a robust toolkit of short-term epigenetic cytoprotective responses designed to “buy time” and increase the chance of acquiring long-term resistance.

scholarly journals Fentanyl vapor self-administration model in mice to study opioid addiction

2020 ◽  
Vol 6 (32) ◽  
pp. eabc0413 ◽  
Author(s):  
K. Moussawi ◽  
M. M. Ortiz ◽  
S. C. Gantz ◽  
B. J. Tunstall ◽  
R. C. N. Marchette ◽  
...  
Keyword(s):  
Mouse Model ◽  
Opioid Addiction ◽  
Dopamine Neurons ◽  
Drug Intake ◽  
Self Administration ◽  
Protracted Abstinence ◽  
Electrophysiological Recordings ◽  
Lower Amplitude ◽  
The Many ◽  
Intravenous Catheterization

Intravenous drug self-administration is considered the “gold standard” model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABAB receptor–dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.

A study on the mediating role of halal perception: determinants and consequence reflections

2016 ◽  
Vol 7 (3) ◽  
pp. 288-302 ◽  
Author(s):  
Suraiya Ishak ◽  
Abd Hair Awang ◽  
Mohd Yusof Hussain ◽  
Zaimah Ramli ◽  
Sarmila Md Sum ◽  
...  
Keyword(s):  
Food Products ◽  
Specific Model ◽  
Purchase Decision ◽  
Self Administration ◽  
Content Type ◽  
Independent Variables ◽  
Mediating Role ◽  
Extrinsic Cues ◽  
Relationship Of

Purpose The purpose of this paper is to examine potential determinants of halal perception and to validate the mediating model of halal perception on purchasing decision of Malaysian consumers. Design/methodology/approach This study uses a survey to obtain the relevant data. The survey involved self-administration of questionnaires to 420 consumers and 96 per cent responded. The questionnaire consists of four sections designed to obtain information on demography, halal perception, determinants of halal perception and purchase decision. Findings The main finding reiterates the role of credible signals in credence items purchased as suggested by the signaling theory. Halal perception has association with respondents’ purchase decision. Thus, it highlights that halal perception is the mediating variable that intervenes in the relationship of a few independent variables and the purchase decision trends. The independent variables such as manufacturer identity, product label, physical product and packaging as well country of origin are considered to be important extrinsic cues that deliver messages regarding the halal of certain food products. The association of the four variables with halal perception is also found to be significant. Originality/value The originality of this study lies in its attempt to explore the role of halal perception in the marketing of food products especially within the scope of a Muslim’s market. Besides, this study attempts to investigate the halal issue based on a specific model that includes potential variables and the intervening role of halal perception.

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