Drug-related Behaviors Research Articles

Pharmacokinetics and thermal anti-nociceptive effects of oral morphine in horses.

Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed. Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration. Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses.

Roadblocks for Successful Treatment in Opioid Substitution Therapy Center in India: An Opinion based on Observation

In India, opioid addiction is a serious emerging problem. Opioid substitution therapy (OST), particularly buprenorphine, has been shown to be very cost-effective and has significant evidence of reduced drug-related HIV risk behaviors, crime, and illegal opioid usage. Raising the standard of living and enhancing public health is one of the main goals of this therapy, with a special emphasis on the center’s efforts to promote harm reduction. However, incidents of reported patient abuse or misuse of these drugs frequently lead to unfavourable opinions of this crucial life-saving procedure. Therefore, the administration and government must move immediately to address the issue.

Factors Associated with an Increased Risk of Opioid Misuse Among Patients with Non-Cancer Pain in Malaysian Pain Clinic Settings

ABSTRACT This study examined the factors associated with a high risk of opioid misuse among patients receiving opioid treatment for their non-cancer pain in Malaysian pain clinics. The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), a validated instrument for predicting the risk of aberrant drug-related behaviors, were used as a proxy to indicate risk of opioid misuse. Data analysis was stratified into high-risk and low-risk patient groups. Patient factors assessed included pain intensity, pain interference with daily activities, and health-related quality of life. Prescription opioid exposure was examined via patient medical and prescription records review. Among the 61 patients recruited, 62.3% scored ≥18 on the SOAPP-R, which indicates a high risk for opioid misuse. Factors associated with a high risk of opioid misuse were found to be high level of pain interference with daily activities, poorer mental health, and younger age. High-risk patients were found to be prescribed a lower mean daily opioid dose of <20 mg/day compared to low-risk patients (20–49 mg/day). This highlights the need for further research to distinguish aberrant drug-related behaviors due to inadequate pain management from that of actual prescription opioid misuse among non-cancer pain patients attending pain clinics.

The Prevalence of and Trend in Drug Use among Adolescents in Mississippi and the United States: Youth Risk Behavior Surveillance System (YRBSS) 2001-2021.

Mississippi youth are demographically unique compared to those of the nation. The aim of the study was to examine the drug use among adolescents in Mississippi compared to that in the US, which included determining prevalence and trends in drug use as well as drugs on school property and estimating the differences in drug use prevalence by gender and by race. National and Mississippi Youth Risk Behavior Surveillance System (YRBSS) data from 2001 to 2021 were obtained for analysis. Summary statistics, prevalence ratio, and survey Chi-squared tests of independence statistics were generated for the comparison for all students, and by gender and race separately. Trend analysis was conducted using logistic regression combined with joinpoint regression. The six survey questions being studied were the following: have you ever used marijuana, an inhalant, heroin, methamphetamines, or injected drugs, and were you offered, sold, or given an illegal drug on school property during the last 12 months. Survey packages in R were used to account for the complex sampling design of YRBSS data. On the national level, all six drug-related risk behaviors being studied showed a significant decrease from 2001 to 2021. In Mississippi, however, only "ever used marijuana" showed a decrease trend, while three remain unchanged, and two increased. The 2021 YRBSS data show that Mississippi adolescents exhibited a significantly higher prevalence of drug use, and are more likely to be offered, sold or given an illegal drug on school property. This research showed detailed findings on drug use-related issues in Mississippi, which is alarming. This poses an important challenge for public health in Mississippi and sounds an urgent call for drug use intervention among Mississippi adolescents. More concerted actions at the community, school and government level are needed for reducing youth drug use and controlling the drug traffic on school property.

The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

The multiple faces of footshock punishment in animal research on addiction

Continued drug use despite negative consequences is a hallmark of addiction commonly modelled in rodents using punished drug intake. Over the years, addiction research highlighted two subpopulations of punishment sensitive and resistant animals. While helpful to interrogate the neurobiology of drug-related behaviors, these procedures carry some weaknesses that need to be recognized and eventually defused. Mainly focusing on footshock-related work, we will first discuss the criteria used to define punishment-resistant animals and how their relative arbitrariness may impact our findings. With the overarching goal of improving our interpretation of the punishment-resistant phenotype, we will evaluate how tailored punishment protocols may better apprehend resistance to punishment, and how testing the robustness of punishment resistance could yield new results and strengthen interpretations. Second, we will question whether and to what extent punishment sensitivity, as currently defined, is reflective of abstinence and suggest that punishment resistance is, in fact, a prerequisite to model abstinence from addiction. Again, we will examine how challenging the robustness of the punishment-sensitive phenotype may help to better characterize it. Finally, we will evaluate whether diminished relapse-like behavior after repeated punishment-induced abstinence could not only contribute to better understand the mechanisms of abstinence, but also uniquely model progressive recovery (i.e., after repeated failed attempts at recovery) which is the norm in people with addiction. Altogether, by questioning the strengths and weaknesses of our models, we would like to open discussions on the different ways we interpret punishment sensitivity and resistance and the aspects that remain to be explored.

Associations among drug acquisition and use behaviors, psychosocial attributes, and opioid-involved overdoses

AimsThis study sought to develop and assess an exploratory model of how demographic and psychosocial attributes, and drug use or acquisition behaviors interact to affect opioid-involved overdoses.DesignWe conducted exploratory and confirmatory factor analysis (EFA/CFA) to identify a factor structure for ten drug acquisition and use behaviors. We then evaluated alternative structural equation models incorporating the identified factors, adding demographic and psychosocial attributes as predictors of past-year opioid overdose.Setting and participantsWe used interview data collected for two studies recruiting opioid-misusing participants receiving services from a community-based syringe services program. The first investigated current attitudes toward drug-checking (N = 150). The second was an RCT assessing a telehealth versus in-person medical appointment for opioid use disorder treatment referral (N = 270).MeasurementsDemographics included gender, age, race/ethnicity, education, and socioeconomic status. Psychosocial measures were homelessness, psychological distress, and trauma. Self-reported drug-related risk behaviors included using alone, having a new supplier, using opioids with benzodiazepines/alcohol, and preferring fentanyl. Past-year opioid-involved overdoses were dichotomized into experiencing none or any.FindingsThe EFA/CFA revealed a two-factor structure with one factor reflecting drug acquisition and the second drug use behaviors. The selected model (CFI = .984, TLI = .981, RMSEA = .024) accounted for 13.1% of overdose probability variance. A latent variable representing psychosocial attributes was indirectly associated with an increase in past-year overdose probability (β = .234, p = .001), as mediated by the EFA/CFA identified latent variables: drug acquisition (β = .683, p < .001) and drug use (β = .567, p = .001). Drug use behaviors (β = .287, p = .04) but not drug acquisition (β = .105, p = .461) also had a significant, positive direct effect on past-year overdose. No demographic attributes were significant direct or indirect overdose predictors.ConclusionsPsychosocial attributes, particularly homelessness, increase the probability of an overdose through associations with risky drug acquisition and drug-using behaviors. Further research is needed to replicate these findings with populations at high-risk of an opioid-related overdose to assess generalizability and refine the metrics used to assess psychosocial characteristics.

CRIMINAL LIABILITY FOR DRUG USE AND DRUG INTOXICATION

The article is dedicated to the study of criminally punishable actions related to narcotics and psychotropic substances (manufacturing, acquisition, possession, transportation, dispatch, etc.), which are committed without the intent to sell and defined in Part 1 of Article 309 of the Criminal Code of Ukraine as forms of the objective side. The authors drew attention to practical situations where a person attempts to ingest (swallow) a purchased narcotic or psychotropic substance in order to evade criminal liability under Part 1 of Article 309 of the Criminal Code. When ingesting such a narcotic substance in non-public places, there is no criminal liability under Ukrainian legislation; only the presence of a public place allows for the qualification of the person’s actions under Article 316 of the Criminal Code. Also, there is no criminal liability when a person is in a public or non-public place in a state of “narcotic intoxication.” In the authors’ opinion, these are shortcomings of the criminal legislation that require correction by supplementing the objective side of Part 1 of Article 309 with new forms related to “drug use” (in any location, not just public) and “being under the influence of narcotics”. Based on the research findings, the authors proposed to present the objective side of Part 1 of Article 309 of the Criminal Code of Ukraine in the following wording: “Illegal production, manufacturing, acquisition, possession, transportation, dispatch, or use of narcotic drugs, psychotropic substances, or their analogues without the intent to sell, as well as being under the influence of narcotics, are punishable by...”. The authors’ proposed amendment to Part 1 of Article 309 of the Criminal Code should function as a general criminal law norm regulating drug use in any location, while the existing Article 316, “Illegal Public Drug Use,” should remain a specific provision applied to cases of drug use in public places. In the authors’ opinion, expanding the content of the objective side in Part 1 of Article 309 by including additional forms will help ensure effective counteraction to drug-related behavior and will have a significant preventive impact on potential drug offenders.

INTERVENSI APOTEKER MENUNJANG PERBAIKAN PERILAKU BEROBAT PENDERITA HIPERTENSI

Based on Riskesdas data (2018), the prevalence of hypertension in South Kalimantan was 10.81% or higher in 2020 compared to the national average of 8.8%. High blood pressure can increase the risk of cardiovascular disease when combined with risk factors like obesity, bad eating habits, smoking, and a sedentary lifestyle. A strategy that incorporates the pharmacist's reminders and motivation through the use of short messaging services (SMS) and modified brief counseling is required to help patients behave better when taking drugs in order to achieve therapeutic success. The purpose of the study is to determine how both interventions affected the drug use of street hypertensive patients at X Hospital Banjarmasin. With a Randomized Pre-test – Post-test Control Group Design, the study project is an experimental quota. The prospective data collection was done on road nursing patients. 34 patients (or 50% of the total) were assigned to the treatment group, and 34 individuals (or 50% of the total) were assigned to the control group, after meeting the inclusion criteria of 68 hypertensive patients. Drug-related behavior questionnaires and interviews were used to gather data. Pharmacists who administered both of these programs found that the treatment group's drug behavior score increased significantly (p&lt;0,05).

Two Problems About Moral Responsibility in The Context of Addiction

Can addiction be credibly invoked as an excuse for moral harms secondary to particular decisions to use drugs? This question raises two distinct sets of issues. First, there is the question of whether addiction is the sort of consideration that could, given suitable assumptions about the details of the case, excuse or mitigate moral blameworthiness. Most discussions of addiction and moral responsibility have focused on this question, and many have argued that addiction excuses. Here I articulate what I take to be the best argument for this view, based on the substantial difficulty that people with severe addiction experience in controlling drug-related behavior. This, I argue, may in some cases be sufficient to ground a mitigating excuse, given the way in which addiction undermines agents’ responsiveness to relevant moral reasons to do otherwise. Much less attention has been devoted to a second set of issues that critically affect the possibility of applying this mitigating excuse in particular cases, derived from the ambivalent nature of agential control in addiction. In order to find a fitting response to moral harm, the person with the right standing to blame must make a judgment about the extent to which the agent possessed certain morally relevant capacities at the time of the act. In practice, this will often prove tremendously difficult to assess. The ethical challenge for the person with the right standing to blame is fundamentally one of making a judgment about matters that seem underdetermined by the available evidence.

‘The general concept is a safer use approach’: how image and performance enhancing drug coaches negotiate safety through community care

Background Drug coaches are a novel extension of traditional personal trainers who play a significant role providing support and shaping drug-related behaviours for people who use image and performance enhancing drugs (IPEDs). They constitute a critical domain for everyday risk management, where substance use, and its associated harms are influenced by social exchange. This study investigated how IPED coaches negotiate safety within the community through the provision of their services and the partnerships they form with clients. Method Ten IPED coaches, selected through purposive sampling, engaged in semi-structured interviews (32–57 minutes in length) exploring the way in which they operate in their field of practice. Iterative inductive analysis was applied to the transcripts, enhanced by discussions among researchers and an independent coder. Results The findings are organised under three categories, revealing the nuanced strategies and identities of IPED coaches, emphasising harm reduction and optimising ‘gains’ in IPED use. These coaches play a significant role in harm reduction, wielding their ‘chemical capital’ and lived experience to integrate nuanced harm reduction strategies into their partnerships with clients. Conclusion Embodying a model of peer-driven knowledge exchange and emphasising open and inclusive discourse IPED coaches offer a vehicle toward integrated harm reduction strategies.

Hippocampal D1-like dopamine receptor as a novel target for the effect of cannabidiol on extinction and reinstatement of methamphetamine-induced CPP

Methamphetamine (METH) is a major health problem without effective pharmacological treatment. Cannabidiol (CBD), a component of the Cannabis sativa plant, is believed to have the potential to inhibit drug-related behavior. However, the neurobiological mechanisms responsible for the effects of CBD remain unclear. Several studies have proposed that the suppressing effects of CBD on drug-seeking behaviors could be through the modulation of the dopamine system. The hippocampus (HIP) D1-like dopamine receptor (D1R) is essential for forming and retrieving drug-associated memory. Therefore, the present study aimed to investigate the role of D1R in the hippocampal CA1 region on the effects of CBD on the extinction and reinstatement of METH-conditioned place preference (CPP). For this purpose, different groups of rats over a 10-day extinction period were administered different doses of intra-CA1 SCH23390 (0.25, 1, or 4 μg/0.5 μl, Saline) as a D1R antagonist before ICV injection of CBD (10 μg/5 μl, DMSO12%). In addition, a different set of animals received intra-CA1 SCH23390 (0.25, 1, or 4 μg/0.5 μl) before CBD injection (50 μg/5 μl) on the reinstatement day. The results revealed that the highest dose of SCH23390 (4 μg) significantly reduced the accelerating effects of CBD on the extinction of METH-CPP (P < 0.01). Furthermore, SCH23390 (1 and 4 μg) in the reinstatement phase notably reversed the preventive effects of CBD on the reinstatement of drug-seeking behavior (P < 0.05 and P < 0.001, respectively). In conclusion, the current study revealed that CBD made a shorter extinction period and suppressed METH reinstatement in part by interacting with D1-like dopamine receptors in the CA1 area of HIP.

Post-transcriptional regulation and subcellular localization of G-protein γ7 subunit: implications for striatal function and behavioral responses to cocaine.

The striatal D1 dopamine receptor (D1R) and A2a adenosine receptor (A2aR) signaling pathways play important roles in drug-related behaviors. These receptors activate the Golf protein comprised of a specific combination of αolfβ2γ7 subunits. During assembly, the γ7 subunit sets the cellular level of the Golf protein. In turn, the amount of Golf protein determines the collective output from both D1R and A2aR signaling pathways. This study shows the Gng7 gene encodes multiple γ7 transcripts differing only in their non-coding regions. In striatum, Transcript 1 is the predominant isoform. Preferentially expressed in the neuropil, Transcript 1 is localized in dendrites where it undergoes post-transcriptional regulation mediated by regulatory elements in its 3' untranslated region that contribute to translational suppression of the γ7 protein. Earlier studies on gene-targeted mice demonstrated loss of γ7 protein disrupts assembly of the Golf protein. In the current study, morphological analysis reveals the loss of the Golf protein is associated with altered dendritic morphology of medium spiny neurons. Finally, behavioral analysis of conditional knockout mice with cell-specific deletion of the γ7 protein in distinct populations of medium spiny neurons reveals differential roles of the Golf protein in mediating behavioral responses to cocaine. Altogether, these findings provide a better understanding of the regulation of γ7 protein expression, its impact on Golf function, and point to a new potential target and mechanisms for treating addiction and related disorders.

Safe beats down under: investigating the support of drug checking at a regional festival in the Northern Territory, Australia

Background In the context of Australian music festivals, including those in the Northern Territory (NT), drug-related harms persist. This study focused on gathering local insights into drug-related behaviours and attitudes, particularly regarding drug checking, among NT festival attendees. Methods In May 2022, attendees (aged 16+) at a single-day multi-genre music festival in the NT were surveyed onsite about their drug use and harm reduction behaviours. Logistic regression was employed to explore factors influencing attitudes and preferences toward drug checking. Results Out of 539 participants, 40% reported recent drug use in the past month. About 12% planned drug use at the festival. Notably, 73% supported drug checking, with 81% approval among people who use drugs. Older participants (>25 years) had 2.6 times (p = .001) greater odds of supporting drug checking. Participants with recent drug use had 2.1 times (p = .006) greater odds of supporting it. Among those opting for drug checking (n = 270), people who have recently used drugs had 5.5 times (p <.001) greater odds of preferring an onsite service. Additionally, 67% believed any drug checking service increased their safety. Conclusions The study reveals NT festivalgoers’ widespread support for drug checking and suggests the need for on-site drug checking services in the NT.

Isradipine, an L-type calcium channel blocker, attenuates cocaine effects in mice by reducing central glutamate release

Substance abuse disorder is a chronic condition for which pharmacological treatment options remain limited. L-type calcium channels (LTCC) have been implicated in drug-related plasticity and behavior. Specifically, dopaminergic neurons in the mesocorticolimbic pathway express Cav1.2 and Cav1.3 channels, which may regulate dopaminergic activity associated with reward behavior. Therefore, this study aimed to investigate the hypothesis that pre-administration of the LTCC blocker, isradipine can mitigate the effects of cocaine by modulating central glutamatergic transmission. For that, we administered isradipine at varying concentrations (1, 7.5, and 15 μg/μL) via intracerebroventricular injection in male Swiss mice. This pretreatment was carried out prior to subjecting animals to behavioral assessments to evaluate cocaine-induced locomotor sensitization and conditioned place preference (CPP). The results revealed that isradipine administered at a concentration of 1 μg/μL effectively attenuated both the sensitization and CPP induced by cocaine (15 mg/kg, via i. p.). Moreover, mice treated with 1 μg/μL of isradipine showed decreased presynaptic levels of glutamate and calcium in the cortex and hippocampus as compared to control mice following cocaine exposure. Notably, the gene expression of ionotropic glutamate receptors, AMPA, and NMDA, remained unchanged, as did the expression of Cav1.2 and Cav1.3 channels. Importantly, these findings suggest that LTCC blockage may inhibit behavioral responses to cocaine, most likely by decreasing glutamatergic input in areas related to addiction.

Consented indicators for the evaluation of integrated strategies of community health promotion targeting children and adolescents: results of an eDelphi.

To date, there is no consensus on indicators for the evaluation of integrated community-based interventions for health promotion and prevention targeting children and adolescents. This study aims at consenting on a scoped set of indicators to evaluate integrated community-based interventions. Out of 738 indicators derived from a literature search, we preselected 94 indicators allotted to 20 domains based on an internal quality appraisal and consensus process and conducted an eDelphi procedure to assess their relevance in view of experts. Experts were recruited in the field of public health, health sciences and communal health promotion in practice and were invited as participants in this eDelphi. During the eDelphi, 47 experts rated the relevance of 94 indicators in two rounds. Consensus was defined as agreement of 75% (or above). After round 1, 27 indicators among 11 consented subdomains reached a consensus on relevance. After round 2, a total of 36 indicators reached consensus on relevance in 9 subdomains (such as socioeconomic factors, health education, nutrition and physical activity, oral health, overall health status, specific health conditions, drug related behavior, exposure to drugs and violence, family factors). These identified indicators may provide a basis for evaluation concepts of integrated community-based interventions for children and adolescents to inform stakeholders about intervention impacts.

Cilia loss on distinct neuron populations differentially alters cocaine-induced locomotion and reward.

Neuronal primary cilia are being recognized for their role in mediating signaling associated with a variety of neurobehaviors, including responses to drugs of abuse. They function as signaling hubs, enriched with a diverse array of G-protein coupled receptors (GPCRs), including several associated with motivation and drug-related behaviors. However, our understanding of how cilia regulate neuronal function and behavior is still limited. The objective of the current study was to investigate the contributions of primary cilia on specific neuronal populations to behavioral responses to cocaine. To test the consequences of cilia loss on cocaine-induced locomotion and reward-related behavior, we selectively ablated cilia from dopaminergic or GAD2-GABAergic neurons in mice. Cilia ablation on either population of neurons failed to significantly alter acute locomotor responses to cocaine at a range of doses. With repeated administration, mice lacking cilia on GAD2-GABAergic neurons showed no difference in locomotor sensitization to cocaine compared to wild-type (WT) littermates, whereas mice lacking cilia on dopaminergic neurons exhibited reduced locomotor sensitization to cocaine at 10 and 30 mg/kg. Mice lacking cilia on GAD2-GABAergic neurons showed no difference in cocaine conditioned place preference (CPP), whereas mice lacking cilia on dopaminergic neurons exhibited reduced CPP compared to WT littermates. Combined with previous findings using amphetamine, our results show that behavioral effects of cilia ablation are cell- and drug type-specific, and that neuronal cilia contribute to modulation of both the locomotor-inducing and rewarding properties of cocaine.

Activity space during treatment with medication for opioid use disorder: Relationships with personality, mood, and drug use

IntroductionActivity space in people with substance use disorders (SUDs) has been assessed for theoretical reasons and for detection/prevention of relapse. In this observational study, we relate passively obtained activity space measures to mental states and behaviors relevant to the success of treatment for opioid use disorder. Our long-term goal is to use such data to assess risk in real time and to recognize when SUD patients might benefit from a just-in-time intervention. MethodsWe used GPS data from 238 urban residents in the first 16 weeks of stabilization on medication for opioid use disorder to test preregistered hypotheses about activity space (distance traveled, number of locations, time spent moving, and psychosocial-hazard levels of neighborhoods where participants spent time) in relation to certain static variables (personality, mood propensities) and time-varying treatment-relevant behaviors such as craving and use of opioids and cocaine. ResultsThe most consistent findings were that 1) mobility decreased over the course of the study; 2) neuroticism was associated with overall lower mobility; 3) trait-like positive mood (averaged from momentary ratings) was associated with higher mobility; 4) participants who used cocaine more frequently had lower mobility; 5) early in treatment, participants spent less time moving (i.e., were more sedentary) on days when they were craving. Some of these findings were in the expected direction (i.e., the ones involving neuroticism and positive mood), and some were opposite to the expected direction (i.e., we expected cocaine use to be associated with higher mobility); others (e.g., changes in mobility over time or in relation to craving) involved nondirectional hypotheses. ConclusionsReal-time information that patients actively provide is valuable for assessing their current state, but providing this information can be burdensome. The current results indicate that certain static or passively obtained data (personality variables and GPS-derived mobility information) are relevant to time-varying, treatment-relevant mental states and drug-related behavior, and therefore might be useful when incorporated into algorithms for detecting need for intervention in real time. Further research should assess how population-specific these relationships are, and how these passive measures can best be combined with low temporal-density, actively-provided data to obtain valid, reliable assessments with minimal burden.

Amphetamine-induced dopamine release in rat: Whole-brain spatiotemporal analysis with [11C]raclopride and positron emission tomography.

Whole-brain mapping of drug effects are needed to understand the neural underpinnings of drug-related behaviors. Amphetamine administration is associated with robust increases in striatal dopamine (DA) release. Dopaminergic terminals are, however, present across several associative brain regions, which may contribute to behavioral effects of amphetamine. Yet the assessment of DA release has been restricted to a few brain regions of interest. The present work employed positron emission tomography (PET) with [11C]raclopride to investigate regional and temporal characteristics of amphetamine-induced DA release across twenty sessions in adult female Sprague Dawley rats. Amphetamine was injected intravenously (2 mg/kg) to cause displacement of [11C]raclopride binding from DA D2-like receptors, assessed using temporally sensitive pharmacokinetic PET model (lp-ntPET). We show amphetamine-induced [11C]raclopride displacement in the basal ganglia, and no changes following saline injections. Peak occupancy was highest in nucleus accumbens, followed by caudate-putamen and globus pallidus. Importantly, significant amphetamine-induced displacement was also observed in several extrastriatal regions, and specifically in thalamus, insula, orbitofrontal cortex, and secondary somatosensory area. For these, peak occupancy occurred later and was lower as compared to the striatum. Collectively, these findings demonstrate distinct amphetamine-induced DA responses across the brain, and that [11C]raclopride-PET can be employed to detect such spatiotemporal differences.

Utility of the Zebrafish Model for Studying Neuronal and Behavioral Disturbances Induced by Embryonic Exposure to Alcohol, Nicotine, and Cannabis.

It is estimated that 5% of pregnant women consume drugs of abuse during pregnancy. Clinical research suggests that intake of drugs during pregnancy, such as alcohol, nicotine and cannabis, disturbs the development of neuronal systems in the offspring, in association with behavioral disturbances early in life and an increased risk of developing drug use disorders. After briefly summarizing evidence in rodents, this review focuses on the zebrafish model and its inherent advantages for studying the effects of embryonic exposure to drugs of abuse on behavioral and neuronal development, with an emphasis on neuropeptides known to promote drug-related behaviors. In addition to stimulating the expression and density of peptide neurons, as in rodents, zebrafish studies demonstrate that embryonic drug exposure has marked effects on the migration, morphology, projections, anatomical location, and peptide co-expression of these neurons. We also describe studies using advanced methodologies that can be applied in vivo in zebrafish: first, to demonstrate a causal relationship between the drug-induced neuronal and behavioral disturbances and second, to discover underlying molecular mechanisms that mediate these effects. The zebrafish model has great potential for providing important information regarding the development of novel and efficacious therapies for ameliorating the effects of early drug exposure.