SciCombinator

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Concept: Drug addiction

409

We propose that highly processed foods share pharmacokinetic properties (e.g. concentrated dose, rapid rate of absorption) with drugs of abuse, due to the addition of fat and/or refined carbohydrates and the rapid rate the refined carbohydrates are absorbed into the system, indicated by glycemic load (GL). The current study provides preliminary evidence for the foods and food attributes implicated in addictive-like eating.

Concepts: Nutrition, Food, Drug addiction, Addiction, Pharmacokinetics, Carbohydrate, Glycemic index, Glycemic load

332

Background The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. Methods We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. Results A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. Conclusions In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875 .).

Concepts: Clinical trial, Smoking, Tobacco, Tobacco smoking, Cigarette, Nicotine, Drug addiction, Addiction

326

The importance of exercise for health and neurogenesis is becoming increasingly clear. Wheel running is often used in the laboratory for triggering enhanced activity levels, despite the common objection that this behaviour is an artefact of captivity and merely signifies neurosis or stereotypy. If wheel running is indeed caused by captive housing, wild mice are not expected to use a running wheel in nature. This however, to our knowledge, has never been tested. Here, we show that when running wheels are placed in nature, they are frequently used by wild mice, also when no extrinsic reward is provided. Bout lengths of running wheel behaviour in the wild match those for captive mice. This finding falsifies one criterion for stereotypic behaviour, and suggests that running wheel activity is an elective behaviour. In a time when lifestyle in general and lack of exercise in particular are a major cause of disease in the modern world, research into physical activity is of utmost importance. Our findings may help alleviate the main concern regarding the use of running wheels in research on exercise.

Concepts: Drug addiction, Motivation, Psychiatry, Madagascar, Stretching, Stereotypy

315

Illegal drug use continues to be a major threat to community health and safety. We used international drug surveillance databases to assess the relationship between multiple long-term estimates of illegal drug price and purity.

Concepts: Drug, Drug addiction, Heroin, Occupational safety and health, MDMA, Illegal drug trade, Single Convention on Narcotic Drugs

194

Nicotine is known as the drug that is responsible for the addicted behaviour of tobacco users, but it has poor reinforcing effects when administered alone. Tobacco product design features enhance abuse liability by (A) optimising the dynamic delivery of nicotine to central nervous system receptors, and affecting smokers' withdrawal symptoms, mood and behaviour; and (B) effecting conditioned learning, through sensory cues, including aroma, touch and visual stimulation, to create perceptions of pending nicotine reward. This study examines the use of additives called ‘pyrazines’, which may enhance abuse potential, their introduction in ‘lights’ and subsequently in the highly market successful Marlboro Lights (Gold) cigarettes and eventually many major brands.

Concepts: Central nervous system, Nervous system, Tobacco, Cigarette, Nicotine, Drug addiction, Addiction, Withdrawal

191

The firing of mesolimbic dopamine neurons is important for drug-induced reinforcement, although underlying genetic factors remain poorly understood. In a recent genome-wide association metaanalysis of alcohol intake, we identified a suggestive association of SNP rs26907 in the ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) gene, encoding a protein that mediates Ca(2+)-dependent activation of the ERK pathway. We performed functional characterization of this gene in relation to alcohol-related phenotypes and mesolimbic dopamine function in both mice and adolescent humans. Ethanol intake and preference were decreased in Rasgrf2(-/-) mice relative to WT controls. Accordingly, ethanol-induced dopamine release in the ventral striatum was blunted in Rasgrf2(-/-) mice. Recording of dopamine neurons in the ventral tegmental area revealed reduced excitability in the absence of Ras-GRF2, likely because of lack of inhibition of the I(A) potassium current by ERK. This deficit provided an explanation for the altered dopamine release, presumably linked to impaired activation of dopamine neurons firing. Functional neuroimaging analysis of a monetary incentive-delay task in 663 adolescent boys revealed significant association of ventral striatal activity during reward anticipation with a RASGRF2 haplotype containing rs26907, the SNP associated with alcohol intake in our previous metaanalysis. This finding suggests a link between the RASGRF2 haplotype and reward sensitivity, a known risk factor for alcohol and drug addiction. Indeed, follow-up of these same boys at age 16 y revealed an association between this haplotype and number of drinking episodes. Together, these combined animal and human data indicate a role for RASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse.

Concepts: Ventral tegmental area, Drug addiction, Addiction, Striatum, Dopamine, Mesolimbic pathway, Nucleus accumbens, Reward system

179

To describe drug use, sexual risks and the prevalence of blood-borne viral infections among men who inject image and performance enhancing drugs (IPEDs).

Concepts: Immune system, Epidemiology, Disease, Infectious disease, Risk, Cytomegalovirus, Drug addiction, Malaise

171

Neuroimaging studies using positron emission tomography suggest that reduced dopamine D(2) receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D(3) receptors (D(3)Rs) in the neurobiology of addiction remains unclear, however. Here we report that D(3)R KO (D(3)(-/-)) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D(3)(-/-) mice. In addition, D(3)(-/-) mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadaptative attempt to normalize elevated basal extracellular dopamine. These findings suggest that D(3)R deletion increases vulnerability to cocaine, and that reduced D(3)R availability in the brain may constitute a risk factor for the development of cocaine addiction.

Concepts: Ventral tegmental area, Positron emission tomography, Substantia nigra, Drug addiction, Dopamine, Nucleus accumbens, Putamen, Cocaine

169

Longer periods of recovery reduce the likelihood of relapse, which may be due to a reduced ability of various stimuli to occasion alcohol or drug seeking. However, this hypothesis remains largely uninvestigated.

Concepts: Alcohol, Carbon dioxide, Carbon, Drug addiction, Addiction, Recovery model

169

Dopaminergic neurons of the ventral tegmental area are important components of brain pathways related to addiction. Prolonged exposure of these neurons to moderate concentrations of dopamine (DA) decreases their sensitivity to inhibition by DA, a process called DA-inhibition reversal (DIR). DIR is mediated by phospholipase C and conventional subtype of protein kinase C (cPKC) through concurrent stimulation of D2 and D1-like DA receptors, or by D2 stimulation concurrent with activation of 5-HT(2) or neurotensin receptors. In the present study, we further characterized this phenomenon by use of extracellular recordings in brain slices to examine whether DIR is linked to G protein-coupled receptor kinase-2 (GRK2) or dynamin by assessing DIR in the presence of antagonists of these enzymes. DIR was blocked by β-ARK1 inhibitor, which inhibits GRK2, and by dynasore, which blocks dynamin. Reversal of inhibition by D2 agonist quinpirole was produced by serotonin (50 µM) and by neurotensin (5-10 nM). Serotonin-induced or neurotensin-induced reversal was blocked by β-ARK1 inhibitor, dynasore, or cPKC antagonist 5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo[2,3-a]pyrrolo[3,4c]carbazole-12-propanenitrile (Gö6976). This further characterization of DIR indicates that cPKC, GRK2, and dynamin play important roles in the desensitization of D2 receptors. As drugs of abuse produce persistent increases in DA concentration in the ventral tegmental area, reduction of D2 receptor sensitivity as a result of drug abuse may be a critical factor in the processes of addiction.

Concepts: Signal transduction, Enzyme inhibitor, Receptor antagonist, Dopamine receptor, Serotonin, Drug addiction, Addiction, Dopamine