Many smokers report attempting to quit each year, yet most relapse, in part due to exposure to smoking-related cues. It is hypothesized that extinction of the cue-drug association could be ...facilitated through random nicotine delivery (RND), thus making it easier for smokers to quit. The current study aimed to evaluate the effects of RND on smoking cessation-related outcomes including cigarettes per day (CPD) and exhaled carbon monoxide (CO).
Participants were current smokers (>9 CPD) interested in quitting. Novel trans-mucosal, orally dissolving nicotine films, developed by Bionex Pharmaceuticals, were used in the study. The pharmacokinetic profile of these films was assessed in single (Experiment 1) and multiple-dose (Experiment 2) administrations prior to the smoking cessation study (Experiment 3). In Experiment 3, participants were randomized 1:1:1 to recieve 4 nicotine films per day of either: placebo delivery (0 mg), steady-state delivery (2 mg), or random nicotine delivery (RND) (0 mg or 4 mg). After two weeks, participants were advised to quit (target quit date, TQD) and were followed up 4 weeks later to collect CPD and CO and to measure dependence (Penn State Cigarette Dependence Index; PSCDI) and craving (Questionnaire of Smoking Urges; QSU-Brief). Means and frequencies were used to describe the data and repeated measures ANOVA was used to determine differences between groups.
The pharmacokinetic studies (Experiment 1 and 2) demonstrated that the films designed for this study delivered nicotine as expected, with the 4 mg film delivering a nicotine boost of approximately 12.4 ng/mL across both the single and the multiple dose administration studies. The films reduced craving for a cigarette and were well-tolerated, overall, and caused no changes in blood pressure or heart rate. Using these films in the cessation study (Experiment 3) (n = 45), there was a significant overall reduction in cigarettes smoked per day (CPD) and in exhaled CO, with no significant differences across groups (placebo, steady-state, RND). In addition, there were no group differences in dependence or craving. Adverse events included heartburn, hiccups, nausea, and to a lesser extent, vomiting and anxiety and there were no differences across groups.
Overall, this pilot study found that RND via orally dissolving films was feasible and well tolerated by participants. However, RND participants did not experience a greater reduction in self-reported CPD and exhaled CO, compared with participants in the steady-state and placebo delivery groups. Future studies to evaluate optimal RND parameters with larger sample sizes are needed to fully understand the effect of RND on smoking cessation-related outcomes.
Once Is Too Much Grigson, Patricia Sue; Hajnal, Andras
Behavioral neuroscience,
12/2007, Letnik:
121, Številka:
6
Journal Article
Recenzirano
The present study tested whether presentation of a taste cue would support conditioned suppression of dopamine in the nucleus accumbens (NAcc) following a single taste-drug pairing. Nondeprived male ...Sprague-Dawley rats were given 20-min access to a 0.15% saccharin conditioned stimulus (CS). Immediately thereafter, experimental rats were injected with morphine (15 mg/kg ip); standard controls were injected with saline; and explicitly unpaired controls were injected with morphine, but approximately 24 hr later. All rats were then given one 20-min CS-only test. Microdialysis samples from the NAcc were measured over 20-min intervals before, during, and after CS access on the conditioning and test trial. The results showed that a single saccharin-morphine pairing led to a marked reduction in CS intake, and the reduction in intake was accompanied by a conditioned blunting of the accumbens dopamine response to the saccharin reward cue. In turn, a single exposure to the saccharin cue also blunted the unconditioned dopamine response to morphine. Reward comparison effects, then, are cross-modal, bidirectional, and immediate, resulting in both unconditioned and conditioned changes in brain and behavior.
Deaths related to opioid use have skyrocketed in the United States, leading to a public health epidemic. Research has shown that both biological (genes) and environmental (stress) precursors are ...linked to opioid use. In particular, stress during adolescence-a critical period of frontal lobe development-influences the likelihood of abusing drugs. However, little is known about the biological mechanisms through which adolescent stress leads to long-term risk of opioid use, or whether genetic background moderates this response. Male and female C57BL/6J and BALB/cJ mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence and then tested for morphine locomotor sensitization or morphine consumption in adulthood. To examine possible mechanisms that underlie stress-induced changes in morphine behaviors, we assessed physiological changes in response to acute stress exposure and prefrontal cortex (PFC) miRNA gene expression. Adolescent stress did not influence morphine sensitization or consumption in BALB/cJ animals, and there was limited evidence of stress effects in female C57BL/6J mice. In contrast, male C57BL/6J mice exposed to adolescent CVSS had blunted morphine sensitization compared to control animals; no differences were observed in the acute locomotor response to morphine administration or morphine consumption. Physiologically, C57BL/6J mice exposed to CVSS had an attenuated corticosterone recovery following an acute stressor and downregulation of twelve miRNA in the PFC compared to control mice. The specificity of the effects for C57BL/6J vs. BALB/cJ mice provides evidence of a gene-environment interaction influencing opioid behaviors. However, this conclusion is dampened by limited locomotor sensitization observed in BALB/cJ mice. It remains possible that results may differ to other doses of morphine or other behavioral responses. Long-term differences in stress reactivity or miRNA expression in C57BL/6J mice suggests two possible biological mechanisms to evaluate in future research.
This article reviews current research and cross-disciplinary perspectives on the neuroscience of food reward in animals and humans, examines the scientific hypothesis of food addiction, discusses ...methodological and terminology challenges, and identifies knowledge gaps and future research needs. Topics addressed herein include the role of reward and hedonic aspects in the regulation of food intake, neuroanatomy and neurobiology of the reward system in animals and humans, responsivity of the brain reward system to palatable foods and drugs, translation of craving versus addiction, and cognitive control of food reward. The content is based on a workshop held in 2013 by the North American Branch of the International Life Sciences Institute.
Addiction III: From mouse to man Grigson, Patricia Sue; Hobkirk, Andrea L.
Brain research bulletin,
February 2023, 2023-Feb, 2023-02-00, 20230201, Letnik:
193
Journal Article
•Exendin-4 reduces aversive affective responses (i.e. Liking) to quinine .•Exendin-4 does not alter affective responses (i.e. Liking) to sucrose.•Exendin-4 reduces motivation (i.e. 'wanting') to ...consume quinine.•Exendin-4 does not affect motivation (i.e. wanting) or affective responses (i.e. Liking) during LICL conditioned-taste aversion/avoidance.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is essential for the regulation of food intake and approved for the treatment of type 2 diabetes mellitus and obesity in humans. More recently, GLP-1 has been investigated for its ability to modulate motivation for food and drugs. Reward behavior can be divided into two components: ‘motivational’ (i.e., approach and consummatory behaviors) and ‘affective’ (i.e., perceived palatability). Studies show that GLP-1 analogs reduce the motivation to approach and consume palatable food, but the impact on affective responding is unknown. Thus, the present study tested the effect of the GLP-1 analog, Exendin-4 (Ex-4), on the appetitive response to intraorally delivered sucrose and quinine. Results showed that Ex-4 (2.4ug/kg ip) failed to alter passive drip, appetitive reactions (i.e., mouth movements, tongue protrusions, and lateral tongue protrusions) or aversive reactions (i.e., gapes) to sucrose. Paw-licking, however, was significantly reduced by Ex-4. Treatment with Ex-4 also failed to influence passive drip to quinine, but increased the latency to gape and reduced the total number of gapes emitted. In addition, Ex-4 reduced intake of quinine in water restricted rats, but did not reduce conditioned aversion (i.e., gapes) or avoidance (i.e., reduced intake) of a LiCl-paired saccharin cue. Thus, while Ex-4 had no effect on a learned aversion, it reduced approach and ingestion of sweet and bitter solutions, while leaving the appetitive affective response to the sweet almost intact, and the aversive affective response to the bitter reduced. Treatment with Ex-4, then, differentially modulates appetitive and consummatory components of reward, depending on the valence of the stimulus and whether its valence is learned or innate.
Rats avoid
intake of a gustatory cue following pairings with a drug of abuse, such as
morphine or cocaine. Despite the well-established rewarding properties of these
drugs, the reduction in intake of ...the taste cue has been interpreted as a
conditioned taste aversion for decades. In 1997, I proposed the reward
comparison hypothesis suggesting that rats avoided intake of the drug-associated
taste cue because the value of the taste cue pales in comparison to the highly
rewarding drug of abuse expected in the near future. In this issue of
Behavioral Neuroscience
,
A.C.W. Huang and S. Hsiao (2008)
challenge the
reward comparison hypothesis by showing parallels between amphetamine and
LiCl-induced suppression of CS intake. This commentary addresses the current
state of the reward comparison hypothesis in the context of the experiments
completed by Huang and Hsiao and their new task-dependent drug effects
hypothesis.
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