scholarly journals 3207 Relation between Dopamine Transporter (DAT1) polymorphism and subjective effects of alcohol among non-dependent drinkers

2019 ◽  
Vol 3 (s1) ◽  
pp. 154-154
Author(s):  
Soundarya Soundararajan ◽  
Bethany L. Stangl ◽  
Courtney L. Vaughan ◽  
Hui Sun ◽  
Falk Lohoff ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Subjective Effects ◽  
Drug Effects ◽  
Computer Assisted ◽  
Self Administration ◽  
Gene Variation ◽  
Breath Alcohol ◽  
Dat1 Gene ◽  
Alcohol Response ◽  
Alcohol Seeking

OBJECTIVES/SPECIFIC AIMS: Dopamine transporter (DAT1) gene variation is associated with reward-related phenotypes including alcohol response. There is also evidence for a potential moderating role for mu-opioid receptor (OPRM1) gene variation on the relationship between DAT1 variation and alcohol response measures. We aimed at studying the interaction between the DAT1 VNTR and OPRM1 A118G polymorphisms on alcohol consumption and subjective responses among non-dependent drinkers. METHODS/STUDY POPULATION: We employed a progressive ratio (PR) paradigm of intravenous alcohol self-administration (IV-ASA) using the Computer-Assisted Infusion System (CAIS) to assess the motivation for alcohol seeking and consumption in a sample of nondependent drinkers. We used the Drug Effects Questionnaire (DEQ) and Biphasic Alcohol Effects Questionnaire (BAES) to assess subjective response. IV-ASA measures included average breath alcohol concentration (BrAC) and total ethanol infused. Peripheral blood samples were collected for genotyping. Ethics approval was obtained from the NIH Addictions Institutional Review Board. RESULTS/ANTICIPATED RESULTS: Fifty participants completed the PR IV-ASA session after informed consent. There were significant interactions between the DAT1 and OPRM1 genotypes in subjective effects of alcohol. Simple main effects analysis showed that DAT1 10a allele carriers that were also OPRM1 G allele carriers had significantly higher scores for several measures: “feel the drug effects” (F (1,46)=6.573, P = 0.014), “feel intoxicated”(F(1,46)=8.613, P = 0.005) and “feeling high” (F(1,46)=10.889, P = 0.002) in DEQ and higher sedation (F(1,46)=4.575, P = 0.038) in BAES. The genotypes statistically significantly predicted average breath alcohol (F (1,61) =3.295, p=0.044) and total ethanol infused(F(1,61)=3.632, p=0.032. DAT1 VNTR and OPRM1 A118G polymorphisms taken together accounted for 6.9 and 7.8% of variations in average breath alcohol and total ethanol infused respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Polymorphic variations in DAT1 and OPRM1 interact with each other in determining subjective effects of alcohol in intravenous alcohol infusion assessing motivation for alcohol seeking and consumption in nondependent drinkers. These epistatic interactions in subjective effects of alcohol are salient in the context of predicting and understanding neurobiological effects of alcohol and thereby the therapeutic responses in treating alcohol use disorders.

scholarly journals Acute Pharmacological Effects and Oral Fluid Concentrations of the Synthetic Cannabinoids JWH-122 and JWH-210 in Humans After Self-Administration: An Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Lucia Martínez ◽  
Nunzia La Maida ◽  
Esther Papaseit ◽  
Clara Pérez-Mañá ◽  
Lourdes Poyatos ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Observational Study ◽  
Oral Fluid ◽  
Short Form ◽  
Subjective Effects ◽  
Synthetic Cannabinoids ◽  
Drug Effects ◽  
Pharmacological Effects ◽  
Self Administration ◽  
Potential Health

Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects of SCs usually is available from intoxication cases and surveys, and few studies on humans after controlled administration or observational/naturalistic studies using standardized measures of cardiovascular and subjective effects are available. The aim of this study was to evaluate the acute pharmacological effects of JWH-122 and JWH-210 recreational consumption in a 4 h observational study and assess their disposition in oral fluid (OF). Sixteen volunteers self-administered 1 mg dose of JWH-122 (n = 8) or 2.25 mg mean dose of JWH-210 (range 2–3 mg, n = 8) by inhalation (smoking). Physiological parameters including blood pressure (systolic and diastolic), heart rate (HR), and cutaneous temperature were measured. A set of visual analog scales, the 49-item short-form version of the Addiction Research Center Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were used for the evaluation of subjective effects. OF was collected at baseline and at 10, 20, and 40 min and 1, 2, 3, and 4 h after self-administration. Statistically significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR were observed after JWH-122 self-administration but not after JWH-210 self-administration. JWH-210 self-administration produced significant changes in subjective drug effects, similar to those induced by THC (intensity, high, good effects, and hunger). The subjective effects following JWH-122 consumption were minimal. The maximal effects were mostly observed 20 min after intake. JWH-122 and JWH 210 OF concentration reached a peak 20 min after administration and could not be detected after 3 h. The results demonstrated a different pattern of effects of these two SCs. Due to the limitations of our observational study, further research with a larger sample and controlled studies are needed to better define the acute pharmacological effect and health risk profile of JWH-122 and JWH-210.

scholarly journals Modeling Motivation for Alcohol in Humans using Traditional and Machine Learning Approaches

2020 ◽  
Author(s):  
Erica Grodin ◽  
Amanda Kay Montoya ◽  
Spencer Bujarski ◽  
Lara A. Ray
Keyword(s):  
Machine Learning ◽  
A Priori ◽  
Progressive Ratio ◽  
Data Driven ◽  
Learning Approaches ◽  
Self Administration ◽  
Breath Alcohol ◽  
Data Driven Approach ◽  
Preclinical And Clinical Studies ◽  
Alcohol Seeking

Given the significant cost of alcohol use disorder, identifying risk factors for alcohol seeking represents a research priority. Prominent addiction theories emphasize the role of motivation in the alcohol seeking process, which has largely been studied using preclinical models. In order to bridge the gap between preclinical and clinical studies, this study examined predictors of motivation for alcohol self-administration using a novel paradigm. Heavy drinkers (n=67) completed an alcohol infusion consisting of an alcohol challenge (target breath alcohol = 60mg%) and a progressive-ratio alcohol self-administration paradigm (maximum breath alcohol 120mg%; ratio requirements range = 20-3,139 response). Growth curve modeling was used to predict breath alcohol trajectories during alcohol self-administration. K-means clustering was used to identify motivated (n=41) and unmotivated (n=26) self-administration trajectories. The data was analyzed using two approaches: a theory-driven test of a-priori predictors and a data-driven, machine learning model. In both approaches, steeper delay discounting, indicating a preference for smaller, sooner rewards, predicted motivated alcohol seeking. The data-driven approach further identified phasic alcohol craving as a predictor of motivated alcohol self-administration. Additional application of this model to AUD translational science and treatment development appear warranted.

Collection of Ego-Centered Network Data with Computer-Assisted Interviews

Methodology ◽  
2006 ◽  
Vol 2 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Joachim Gerich ◽  
Roland Lehner
Keyword(s):  
Survey Methods ◽  
A Priori ◽  
Dynamic Structure ◽  
Computer Assisted ◽  
Network Data ◽  
Great Effort ◽  
Self Administration ◽  
Face To Face ◽  
Full Network

Although ego-centered network data provide information that is limited in various ways as compared with full network data, an ego-centered design can be used without the need for a priori and researcher-defined network borders. Moreover, ego-centered network data can be obtained with traditional survey methods. However, due to the dynamic structure of the questionnaires involved, a great effort is required on the part of either respondents (with self-administration) or interviewers (with face-to-face interviews). As an alternative, we will show the advantages of using CASI (computer-assisted self-administered interview) methods for the collection of ego-centered network data as applied in a study on the role of social networks in substance use among college students.

Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants.

1984 ◽  
Vol 91 (2) ◽  
pp. 251-268 ◽  
Author(s):  
Jane Stewart ◽  
Harriet de Wit ◽  
Roelof Eikelboom
Keyword(s):  
Drug Effects ◽  
The Self ◽  
Self Administration

Selective Decreases in Amphetamine Self-Administration and Regulation of Dopamine Transporter Function in Diabetic Rats

2003 ◽  
Vol 77 (2) ◽  
pp. 132-140 ◽  
Author(s):  
Ruggero Galici ◽  
Aurelio Galli ◽  
David J. Jones ◽  
Teresa A. Sanchez ◽  
Christine Saunders ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Diabetic Rats ◽  
Self Administration

scholarly journals Stress vulnerability promotes an alcohol prone phenotype in a preclinical model of sustained depression

2018 ◽  
Author(s):  
Danai Riga ◽  
Leanne JM Schmitz ◽  
Yvar van Mourik ◽  
Witte JG Hoogendijk ◽  
Taco J De Vries ◽  
...  
Keyword(s):  
Social Defeat ◽  
Preclinical Model ◽  
Self Administration ◽  
Depression Vulnerability ◽  
Stress Vulnerability ◽  
The Social ◽  
Depression Proneness ◽  
Male Wistar Rats ◽  
Alcohol Seeking

AbstractMajor depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

Behavioral and Physiological Effects of Remifentanil and Alfentanil in Healthy Volunteers 

1999 ◽  
Vol 90 (3) ◽  
pp. 718-726 ◽  
Author(s):  
Matthew L. Black ◽  
Joanna L. Hill ◽  
James P. Zacny
Keyword(s):  
Healthy Volunteers ◽  
Dose Range ◽  
Subjective Effects ◽  
Cold Pressor Test ◽  
Drug Effects ◽  
Cold Pressor ◽  
Psychomotor Tests ◽  
Potency Ratio ◽  
Psychomotor Effects ◽  
Double Blinded

Background The subjective and psychomotor effects of remifentanil have not been evaluated. Accordingly, the authors used mood inventories and psychomotor tests to characterize the effects of remifentanil in healthy, non-drug-abusing volunteers. Alfentanil was used as a comparator drug. Methods Ten healthy volunteers were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial in which they received an infusion of saline, remifentanil, or alfentanil for 120 min. The age- and weight-adjusted infusions (determined with STANPUMP, a computer modeling software package) were given to achieve three predicted constant plasma levels for 40 min each of remifentanil (0.75, 1.5, and 3 ng/ml) and alfentanil (16, 32, and 64 ng/ml). Mood forms and psychomotor tests were completed, and miosis was assessed, during and after the infusions. In addition, analgesia was tested at each dose level using a cold-pressor test. Results Remifentanil had prototypic micro-like opioid subjective effects, impaired psychomotor performance, and produced analgesia. Alfentanil at the dose range tested had more mild effects on these measures, and the analgesia data indicated that a 40:1 potency ratio, rather than the 20:1 ratio we used, may exist between remifentanil and alfentanil. A psychomotor test administered 60 min after the remifentanil infusion was discontinued showed that the volunteers were still impaired, although they reported feeling no drug effects. Conclusions The notion that the pharmacodynamic effects of remifentanil are extremely short-lived after the drug is no longer administered must be questioned given our findings that psychomotor effects were still apparent 1 h after the infusion was discontinued.

scholarly journals The GABAB Positive Allosteric Modulator ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats

2017 ◽  
Vol 42 (9) ◽  
pp. 1789-1799 ◽  
Author(s):  
Eric Augier ◽  
Russell S Dulman ◽  
Ruslan Damadzic ◽  
Andrew Pilling ◽  
J Paul Hamilton ◽  
...  
Keyword(s):  
Allosteric Modulator ◽  
Self Administration ◽  
Positive Allosteric Modulator ◽  
Alcohol Seeking
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