Median duration of training sessions was 2 h (IQR 1-3 h); 78% were trained by home health care or specialty pharmacy staff, and 75% were trained at home. Conclusions Survey results show a large ...majority of PI patients currently receiving SCIG reported minimal or no difficulty in learning self-administration.
Evidence suggests that single housing in rats acts as a chronic stressor, raising the possibilities that it contributes to measures of heroin craving and that pair housing ameliorates such measures. ...This study aimed to determine whether pair housing after heroin self-administration reduces the incubation of craving, extinction, and reinstatement of heroin seeking. Single-housed female and male Sprague-Dawley rats underwent daily 6-hr heroin self-administration, wherein active lever presses produced a heroin infusion paired with light/tone cues. One day after self-administration, rats underwent a baseline cued-seeking test wherein active lever presses only produced light/tone cues. Immediately following this cued-seeking test, rats were either pair-housed with weight- and sex-matched naïve rat or remained single-housed for the rest of the study. For 14 days, rats remained in their homecages, after which they underwent a cued-seeking test to assess the incubation of craving compared to their baseline test. Rats then underwent extinction sessions followed by cue-induced and heroin-primed reinstatements. The findings reveal that pair-housed rats did not differ from single-housed rats in terms of the incubation of craving, extinction, or reinstatement of heroin seeking. Additionally, the results did not reveal any evidence of sex-based differences in the study. The present work indicates that pair housing during the forced abstinence period does not alter measures of heroin craving/seeking. These findings suggest that the chronic stress of single housing specifically during forced abstinence does not contribute to the degree of such measures.
Problems with the use of inhalers by patients were noted shortly after the launch of the metered-dose inhaler (MDI) and persist today. We aimed to assess the most common errors in inhaler use over ...the past 40 years in patients treated with MDIs or dry powder inhalers (DPIs).
A systematic search for articles reporting direct observation of inhaler technique by trained personnel covered the period from 1975 to 2014. Outcomes were the nature and frequencies of the three most common errors; the percentage of patients demonstrating correct, acceptable, or poor technique; and variations in these outcomes over these 40 years and when partitioned into years 1 to 20 and years 21 to 40. Analyses were conducted in accordance with recommendations from Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Strengthening the Reporting of Observational Studies in Epidemiology.
Data were extracted from 144 articles reporting on a total number of 54,354 subjects performing 59,584 observed tests of technique. The most frequent MDI errors were in coordination (45%; 95% CI, 41%-49%), speed and/or depth of inspiration (44%; 40%-47%), and no postinhalation breath-hold (46%; 42%-49%). Frequent DPI errors were incorrect preparation in 29% (26%-33%), no full expiration before inhalation in 46% (42%-50%), and no postinhalation breath-hold in 37% (33%-40%). The overall prevalence of correct technique was 31% (28%-35%); of acceptable, 41% (36%-47%); and of poor, 31% (27%-36%). There were no significant differences between the first and second 20-year periods of scrutiny.
Incorrect inhaler technique is unacceptably frequent and has not improved over the past 40 years, pointing to an urgent need for new approaches to education and drug delivery.
Reports of abuse and toxic effects of synthetic cathinones, frequently sold as ‘bath salts’ or ‘legal highs’, have increased dramatically in recent years. One of the most widely used synthetic ...cathinones is 3,4‐methylenedioxypyrovalerone (MDPV). The current study evaluated the abuse potential of MDPV by assessing its ability to support intravenous self‐administration and to lower thresholds for intracranial self‐stimulation (ICSS) in rats. In the first experiment, the rats were trained to intravenously self‐administer MDPV in daily 2‐hour sessions for 10 days at doses of 0.05, 0.1 or 0.2 mg/kg per infusion. The rats were then allowed to self‐administer MDPV under a progressive ratio (PR) schedule of reinforcement. Next, the rats self‐administered MDPV for an additional 10 days under short access (ShA; 2 hours/day) or long access (LgA; 6 hours/day) conditions to assess escalation of intake. A separate group of rats underwent the same procedures, with the exception of self‐administering methamphetamine (0.05 mg/kg per infusion) instead of MDPV. In the second experiment, the effects of MDPV on ICSS thresholds following acute administration (0.1, 0.5, 1 and 2 mg/kg, i.p.) were assessed. MDPV maintained self‐administration across all doses tested. A positive relationship between MDPV dose and breakpoints for reinforcement under PR conditions was observed. LgA conditions led to escalation of drug intake at 0.1 and 0.2 mg/kg doses, and rats self‐administering methamphetamine showed similar patterns of escalation. Finally, MDPV significantly lowered ICSS thresholds at all doses tested. Together, these findings indicate that MDPV has reinforcing properties and activates brain reward circuitry, suggesting a potential for abuse and addiction in humans.
The use and abuse of designer stimulant such as 3,4‐methylenedioxypyrovalerone (MDPV), often sold as “bath salts”, has increased dramatically in recent years.
The present study reveals that MDPV supports robust intravenous self‐administration behavior across a range of doses, leads to escalation of intake with prolonged access, and produces decreases in brain stimulation reward thresholds. Together, these results reveal potent rewarding and reinforcing effects of MDPV, suggestive of a high degree of addiction potential in humans.
Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the ...amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target.
In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion.
Oxytocin Reduces Ethanol Self‐Administration in Mice King, Courtney E.; Griffin, William C.; Luderman, Lauryn N. ...
Alcoholism, clinical and experimental research,
20/May , Letnik:
41, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Background
Excessive ethanol (EtOH) consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important ...therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces EtOH consumption.
Methods
Male C57BL/6J mice were given access to EtOH (20% v/v) using a model of binge‐like drinking (“drinking in the dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2‐bottle choice drinking in the home cage. In addition, EtOH (12% v/v) and sucrose (5% w/v) self‐administration on fixed‐ and progressive‐ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models.
Results
Oxytocin (0, 0.3, 1, 3, or 10 mg/kg) dose dependently reduced EtOH consumption (maximal 45% reduction) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist, and the pattern of contacts (licks) at the EtOH bottle suggested a reduction in motivation to drink EtOH. Oxytocin decreased 2‐bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for EtOH and sucrose in a dose‐related manner. However, oxytocin decreased responding and motivation (breakpoint values) for EtOH at doses that did not alter responding for sucrose.
Conclusions
These results indicate that oxytocin reduces EtOH consumption in different models of self‐administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for EtOH at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Nevertheless, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder.
A series of studies was conducted to examine the effects of the neurohormone oxytocin on alcohol consumption in mice. Results indicated that systemic administration of oxytocin decreased binge‐like alcohol intake in a dose‐related manner (data not shown) and reduced operant oral alcohol self‐administration at doses that did not alter responding for sucrose. These results support an emerging preclinical and clinical literature implicating a potential therapeutic role for oxytocin in alcohol addiction.
A key challenge in developing treatments for neuropsychiatric illness is the disconnect between preclinical models and the complexity of human social behavior. We integrate voluntary social ...self-administration into a rodent model of social stress as a platform for the identification of fundamental brain and behavior mechanisms underlying stress-induced individual differences in social motivation.
Here, we introduced an operant social stress procedure in male and female mice composed of 3 phases: 1) social self-administration training, 2) social stress exposure concurrent with reinforced self-administration testing, and 3) poststress operant testing under nonreinforced and reinforced conditions. We used social-defeat and witness-defeat stress in male and female mice.
Social defeat attenuated social reward seeking in males but not females, whereas witness defeat had no effect in males but promoted seeking behavior in females. We resolved social stress-induced changes to social motivation by aggregating z-scored operant metrics into a cumulative social index score to describe the spectrum of individual differences exhibited during operant social stress. Clustering does not adequately describe the relative distributions of social motivation following stress and is better described as a nonbinary behavioral distribution defined by the social index score, capturing a dynamic range of stress-related alterations in social motivation inclusive of sex as a biological variable.
We demonstrated that operant social stress can detect stable individual differences in stress-induced changes to social motivation. The inclusion of volitional behavior in social procedures may enhance the understanding of behavioral adaptations that promote stress resiliency and their mechanisms under more naturalistic conditions.
Rationale
Reducing nicotine content of inhaled tobacco products may prevent nicotine addiction, but the threshold for nicotine reinforcement has not been systematically evaluated in controlled human ...laboratory studies.
Objectives
The current study uses a novel double-blind placebo-controlled intravenous (IV) nicotine self-administration (NSA) model to determine threshold for subjective effects of nicotine and nicotine reinforcement using a forced choice self-administration procedure.
Methods
Young adults (
n
= 34) had 5 laboratory sessions after overnight nicotine abstinence. In each session, participants sampled and rated the subjective effects of an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg nicotine/70 kg bodyweight) versus saline (placebo), then were given a total of 10 opportunities to self-administer either the IV dose of nicotine or placebo.
Results
Mixed effect models revealed a significant effect of nicotine dose for positive (i.e., “stimulatory” and “pleasurable”;
p
< .0001) effects, but not “aversive” effects during sampling period. Post hoc comparisons showed that higher doses (i.e., 0.1 and 0.2 mg) were associated with greater stimulatory, pleasurable, and physiological effects than placebo and lower doses. Mixed effect models revealed that only the highest dose (i.e., 0.2 mg) was consistently preferred over placebo. Sex differences were generally weak (
p
= .03–.05).
Conclusions
Using our IV nicotine NSA model, the threshold for detecting positive effects of nicotine in young adult smokers is about 0.1 mg, but a higher dose of nicotine, 0.2 mg, is required to produce a consistent nicotine reinforcement. Regarding the regulatory impact, our findings further support the value of nicotine reinforcement threshold as a tobacco regulatory target.
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