Drug-taking Behavior Research Articles

Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats.

Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking. Adult male rats were trained to perform a "simple" or "complex" version of a delayed-match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression. Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence. These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance before drug exposure may predict vulnerability to future drug use.

N-tert-butoxycarbonyl-methylenedioxymethamphetamine, an methylenedioxymethamphetamine derivative, exhibits rewarding and reinforcing effects by increasing dopamine levels.

An N-protected methylenedioxymethamphetamine (MDMA), N-tert-butoxycarbonyl-3,4-methylenedioxymethamphetamine (t-BOC-3,4-MDMA), contains tert-butoxycarbonyl and can remain undetected in the illicit drug market. It is a new type of precursor substance that is not a chemical intermediate and can be converted into a controlled substance, MDMA, by deprotection of the N-tert-butoxycarbonyl group. Categorization of this chemical into a precursor or psychotropic substance is an issue because it is an unprecedented precursor that could have misuse potential. Although MDMA causes rewarding and reinforcing effect through dopaminergic transmission, the misuse potential of t-BOC-3,4-MDMA has not yet been characterized. Here, we aim to evaluate the misuse potential of t-BOC-3,4-MDMA. The response to the drug at a dose of 5 mg/kg was determined by a climbing test, and its rewarding and reinforcing properties were assessed through conditioned place preference and self-administration tests. In the conditioned place preference test, intraperitoneal administration of t-BOC-3,4-MDMA (5 mg/kg) significantly altered place preference in mice. In the self-administration models, t-BOC-3,4-MDMA induced drug-taking behavior at the dose of 0.5 mg/kg/infusion (intravenous) during 2 hr sessions under fixed-ratio schedules in mice. In addition, microdialysis experiments verified that t-BOC-3,4-MDMA impacted the dopamine levels of the brain (striatum) of rats. These experimental results indicate that t-BOC-3,4-MDMA has a potential for misuse. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Role of serotonin neurons in the dorsal raphe nucleus in heroin self-administration and punishment.

One hallmark of substance use disorder is continued drug use despite negative consequences. When drug-taking behavior is punished with aversive stimuli, i.e. footshock, rats can also be categorized into punishment-resistant or compulsive vs. punishment-sensitive or non-compulsive phenotypes. The serotonin (5-hydroxytryptamine, 5-HT) system modulates responses to both reward and punishment. The goal of the current study was to examine punishment phenotypes in heroin self-administration and to determine the role of dorsal raphe nucleus (DRN) 5-HT neurons in both basal and punished heroin self-administration. First, rats were exposed to punished heroin self-administration and neuronal excitability of DRN 5-HT neuronswas compared between punishment-resistant and punishment-sensitive phenotypes using ex vivo electrophysiology. Second, DRN 5-HT neuronal activity was manipulated in vivo during basal and punished heroin self-administration using chemogenetic tools in a Tph2-iCre rat line. While rats separated into punishment-resistant and punishment-sensitive phenotypes for punished heroin self-administration, DRN 5-HT neuronal excitability did not differ between the phenotypes. While chemogenetic inhibition of DRN 5-HT neurons was without effect, chemogenetic activation of DRN 5-HT neurons increased both basal and punished heroin self-administration selectively in punishment-resistant animals. Additionally, the responsiveness to chemogenetic activation of DRN 5-HT neurons in basal self-administration and motivation for heroin in progressive ratio each predicted resistance to punishment. Therefore, our data support the role for the DRN 5-HT system in compulsive heroin self-administration.

Self-administration acquisition latency predicts locomotor sensitivity to cocaine in male rats

Individual differences in drug use emerge soon after initial exposure, and only a fraction of individuals who initiate drug use go on to develop a substance use disorder. Variability in vulnerability to establishing drug self-administration behavior is also evident in preclinical rodent models. Latent characteristics that underlie this variability and the relationship between early drug use patterns and later use remain unclear. Here, we attempt to determine whether propensity to establish cocaine self-administration is related to subsequent cocaine self-administration behavior in male Sprague-Dawley rats (n = 14). Prior to initiating training, we evaluated basal locomotor and anxiety-like behavior in a novel open field test. We then trained rats to self-administer cocaine in daily 3 h cocaine (0.75 mg/kg/infusion) self-administration sessions until acquisition criteria (≥30 active lever presses with ≥70 % responding on the active lever in one session) was met and divided rats into Early and Late groups by median-split analysis based on their latency to meet acquisition criteria. After each rat met acquisition criteria, we gave them 10 additional daily cocaine self-administration sessions. We then conducted a progressive ratio, cocaine-induced locomotor sensitivity test, and non-reinforced cocaine seeking test after two weeks of forced abstinence. Early Learners exhibited significantly less locomotion after an acute injection of cocaine, but the groups did not differ in any other behavioral parameter examined. These results indicate that cocaine self-administration acquisition latency is not predictive of subsequent drug-taking behavior, but may be linked to physiological factors like drug sensitivity that can predispose rats to learn the operant task.

Cannabidiol Protects against the Reinstatement of Oxycodone-Induced Conditioned Place Preference in Adolescent Male but Not Female Rats: The Role of MOR and CB1R.

Cannabidiol (CBD), a phytocannabinoid, appeared to satisfy several criteria for a safe approach to preventing drug-taking behavior, including opioids. However, most successful preclinical and clinical results come from studies in adult males. We examined whether systemic injections of CBD (10 mg/kg, i.p.) during extinction of oxycodone (OXY, 3 mg/kg, i.p.) induced conditioned place preference (CPP) could attenuate the reinstatement of CPP brought about by OXY (1.5 mg/kg, i.p.) priming in adolescent rats of both sexes, and whether this effect is sex dependent. Accordingly, a priming dose of OXY produced reinstatement of the previously extinguished CPP in males and females. In both sexes, this effect was linked to locomotor sensitization that was blunted by CBD pretreatments. However, CBD was able to prevent the reinstatement of OXY-induced CPP only in adolescent males and this outcome was associated with an increased cannabinoid 1 receptor (CB1R) and a decreased mu opioid receptor (MOR) expression in the prefrontal cortex (PFC). The reinstatement of CCP in females was associated with a decreased MOR expression, but no changes were detected in CB1R in the hippocampus (HIP). Moreover, CBD administration during extinction significantly potentialized the reduced MOR expression in the PFC of males and showed a tendency to potentiate the reduced MOR in the HIP of females. Additionally, CBD reversed OXY-induced deficits of recognition memory only in males. These results suggest that CBD could reduce reinstatement to OXY seeking after a period of abstinence in adolescent male but not female rats. However, more investigation is required.

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

Methamphetamine use disorder (MUD) is a chronic, relapsing disease that is characterized by repeated drug use despite negative consequences and for which there are currently no FDA-approved cessation therapeutics. Repeated methamphetamine (METH) use induces long-term gene expression changes in brain regions associated with reward processing and drug-seeking behavior, and recent evidence suggests that methamphetamine-induced neuroinflammation may also shape behavioral and molecular responses to the drug. Microglia, the resident immune cells in the brain, are principal drivers of neuroinflammatory responses and contribute to the pathophysiology of substance use disorders. Here, we investigated transcriptional and morphological changes in dorsal striatal microglia in response to methamphetamine-taking and during methamphetamine abstinence, as well as their functional contribution to drug-taking behavior. We show that methamphetamine self-administration induces transcriptional changes associated with protein folding, mRNA processing, immune signaling, and neurotransmission in dorsal striatal microglia. Importantly, many of these transcriptional changes persist through abstinence, a finding supported by morphological analyses. Functionally, we report that microglial ablation increases methamphetamine-taking, possibly involving neuroimmune and neurotransmitter regulation. In contrast, microglial depletion during abstinence does not alter methamphetamine-seeking. Taken together, these results suggest that methamphetamine induces both short and long-term changes in dorsal striatal microglia that contribute to altered drug-taking behavior and may provide valuable insights into the pathophysiology of MUD.

Working memory performance predicts, but does not reduce, cocaine- and cannabinoid-seeking in adult male rats.

Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking. Adult male rats were trained to perform a 'simple' or 'complex' version of a delayed- match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug-seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression. Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence. These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance prior to drug exposure may predict vulnerability to future drug use.

AM6527, a neutral CB1 receptor antagonist, suppresses opioid taking and seeking, as well as cocaine seeking in rodents without aversive effects

Preclinical research has demonstrated the efficacy of CB1 receptor (CB1R) antagonists in reducing drug-taking behavior. However, clinical trials with rimonabant, a CB1R antagonist with inverse agonist profile, failed due to severe adverse effects, such as depression and suicidality. As a result, efforts have shifted towards developing novel neutral CB1R antagonists without an inverse agonist profile for treating substance use disorders. Here, we assessed AM6527, a CB1R neutral antagonist, in addiction animal models. Our findings revealed that AM6527 did not affect cocaine self-administration under fixed-ratio reinforcement schedules but dose-dependently inhibited it under progressive-ratio reinforcement schedules. Additionally, AM6527 dose-dependently inhibited heroin self-administration under both fixed-ratio and progressive-ratio reinforcement schedules and oral sucrose self-administration under a fixed-ratio reinforcement schedule, as well as cocaine- or heroin-triggered reinstatement of drug-seeking behavior in rats. However, chronic AM6527 administration for five consecutive days significantly inhibited heroin self-administration only during the initial two days, indicating tolerance development. Notably, AM6527 did not produce rewarding or aversive effects by itself in classical electrical intracranial self-stimulation and conditioned place preference tests. However, in optical intracranial self-stimulation (oICSS) maintained by optogenetic stimulation of midbrain dopamine neurons in DAT-cre mice, both AM6527 and rimonabant dose-dependently inhibited dopamine-dependent oICSS behavior. Together, these findings suggest that AM6527 effectively reduces drug-taking and seeking behaviors without rimonabant-like adverse effects. Thus, AM6527 warrants further investigation as a potential pharmacotherapy for opioid and cocaine use disorders.

Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.

The present study used a rat choice model to test how cocaine or heroin economically interacted with two different nondrug reinforcers along the substitute-to-complement continuum. In Experiment 1, the nondrug alternative was the negative reinforcer timeout-from-avoidance (TOA)-that is, rats could press a lever to obtain a period of safety from footshock. One group of rats chose between cocaine and TOA and another group chose between heroin and TOA. The relative prices of the reinforcers were manipulated across phases while controlling for potential income effects. When cocaine was the reinforcer, rats reacted to price changes by increasing their allocation of behavior to the more expensive option, thereby maintaining relatively proportional intake of cocaine and TOA reinforcers across prices, suggesting these reinforcers were complements here. In contrast, when heroin became relatively cheap, rats increased allocation of income to heroin and decreased allocation of income to TOA, suggesting that heroin substituted for safety. Additionally, rats were willing to accept more footshocks when heroin was easily available. In Experiment 2, the nondrug alternative was saccharin, a positive reinforcer. Heroin and saccharin were complements, but there was no consistent effect of price changes on the allocation of behavior between cocaine and saccharin. As a model of the processes that could be involved in human drug use, these results show that drug-taking behavior depends on the type of drug, the type of nondrug alternative available, and the prices of both. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

GPR55 is expressed in glutamate neurons and functionally modulates drug taking and seeking in rats and mice

G protein-coupled receptor 55 (GPR55) has been thought to be a putative cannabinoid receptor. However, little is known about its functional role in cannabinoid action and substance use disorders. Here we report that GPR55 is predominantly found in glutamate neurons in the brain, and its activation reduces self-administration of cocaine and nicotine in rats and mice. Using RNAscope in situ hybridization, GPR55 mRNA was identified in cortical vesicular glutamate transporter 1 (VgluT1)-positive and subcortical VgluT2-positive glutamate neurons, with no detection in midbrain dopamine (DA) neurons. Immunohistochemistry detected a GPR55-like signal in both wildtype and GPR55-knockout mice, suggesting non-specific staining. However, analysis using a fluorescent CB1/GPR55 ligand (T1117) in CB1-knockout mice confirmed GPR55 binding in glutamate neurons, not in midbrain DA neurons. Systemic administration of the GPR55 agonist O-1602 didnt impact ∆9-THC-induced analgesia, hypothermia and catalepsy, but significantly mitigated cocaine-enhanced brain-stimulation reward caused by optogenetic activation of midbrain DA neurons. O-1602 alone failed to alter extracellar DA, but elevated extracellular glutamate, in the nucleus accumbens. In addition, O-1602 also demonstrated inhibitory effects on cocaine or nicotine self-administration under low fixed-ratio and/or progressive-ratio reinforcement schedules in rats and wildtype mice, with no such effects observed in GPR55-knockout mice. Together, these findings suggest that GPR55 activation may functionally modulate drug-taking and drug-seeking behavior possibly via a glutamate-dependent mechanism, and therefore, GPR55 deserves further study as a new therapeutic target for treating substance use disorders.

Unmasking Distorted Reflections: Exploring Body Image, Alcohol, and Drug Use in Nighttime Entertainment Districts

Background: Violence within nighttime entertainment districts (NEDs) has been blamed on problematic masculinity and has predominantly been attributed to excessive alcohol intake and steroid use in men. In this report we conducted two studies to: (1) ascertain whether researchers could act as third-party raters of body weight and muscle mass in NED patrons; and (2) to examine the relationship between body self-image, inebriation, alcohol preloading behaviors and drug use in the NEDs. Methods: Study 1 employed an observational approach to establish inter-rater reliability for ratings of muscle mass and weight. In Study 2 data (n = 2,745) were collected through breathalyzing and questionnaires to examine individuals’ self-image and drinking and drug-taking behaviors. Results: Participants’ self-ratings of muscle and weight significantly differed from researchers’ ratings, with males perceiving themselves as less muscular and females perceiving themselves as heavier. Perceived weight and muscle size did not relate to alcohol levels, but an interaction was found for female steroid users who perceived themselves as less muscular. Conclusions: Findings indicated a distortion in participants’ perceived body image, with a desire for muscularity among both males and females. These results underscore the complex interplay between self-perception, societal ideals, and drug use in young NED patrons.

Attentional biases in abstinent patients with cocaine use disorder: rapid orienting or delayed disengagement?

Addiction-related attentional biases may play a central role in the development and maintenance of drug-seeking and drug-taking behaviors. However, evidence in cocaine dependence is limited and mixed. This study examined the time course and component processes of attentional biases for cocaine-related cues in a sample of 47 outpatients (38 men) with cocaine use disorder (CUD) with varying durations of current abstinence. Reaction times in a visual dot-probe task with two picture exposure durations -500 ms, to assess initial stages of attention, and 2,000 ms, to assess maintained attention- were recorded. We found faster responses to probes replacing cocaine-related vs. matched control pictures in the 500 ms but not in the 2,000 ms condition, indicative of early but not late attentional biases for cocaine cues in abstinent patients with CUD. Further comparisons with a neutral baseline revealed that it was not due to rapid orienting but to delayed disengagement from cocaine-related pictures, being this effect greater the longer the period of current abstinence. Consistent with the incentive-sensitization theory, these data suggest that cocaine-related stimuli maintain the capacity to hold spatial attention in abstinent patients with CUD, even after months of abstinence, highlighting the relevance of carrying out stimulus control to avoid relapses.

Pain medication misuse in the South African spinal cord injury context.

Pain after spinal cord injury (SCI) is debilitating and has been reported to be difficult to treat, despite pharmacological interventions. Pain medication misuse (PMM) and associated individual factors among people with spinal cord injury (PWSCI) are scarce. To determine PMM and the associated factors in PWSCI. Homes of community-dwelling manual wheelchair users with SCI in South Africa. Community-dwelling PWSCI (n = 122) were consecutively sampled and the Pain Medication Questionnaire (PMQ) was used to determine PMM. Descriptive statistics, Fisher's exact test, independent t-tests, and simple linear regression tests were performed using SPSS v27. Testing was conducted at the 0.05 level of significance. Eighty-five per cent of the participants reported the presence of pain and 48.1% of them used pain medication. Forty-four percent of people who used pain medication scored ≥ 30, indicative of serious aberrant drug-taking behaviours. Opioids were mainly used for neuropathic pain and in combination with other types of medications such as anticonvulsants and non-steroidal anti-inflammatories (44.0%). Pain severity and the type of pain medication were found to be predictors of PMM (p < 0.01 respectively). Pain relief after SCI remains difficult to achieve, with an evident high risk of PMM, which may lead to long-lasting side effects, dependency, or overdose. This study has shown the need for the assessment of the potential risk of dependency before prescribing pain medication, particularly opioids to PWSCI.

Immunoassay Urine Drug Testing among Patients Receiving Opioids at a Safety-Net Palliative Medicine Clinic

Background: Few studies have examined the use of immunoassay urine drug testing of cancer patients in palliative care clinics. Objectives: We examined the frequency of immunoassay urine drug test (UDT) abnormalities and the factors associated with aberrancy at a safety-net hospital palliative medicine clinic. Methods: A retrospective review of the electronic medical records of consecutive eligible patients seen at the outpatient palliative medicine clinic in a resource-limited safety-net hospital system was conducted between 1 September 2015 and 31 December 2020. We collected longitudinal data on patient demographics, UDT findings, and potential predictors of aberrant results. Results: Of the 913 patients in the study, 500 (55%) underwent UDT testing, with 455 (50%) having the testing within the first three visits. Among those tested within the first three visits, 125 (27%) had aberrant UDT results; 44 (35%) of these 125 patients were positive for cocaine. In a multivariable regression model analysis of predictors for aberrant UDT within the first three visits, non-Hispanic White race (odds ratio (OR) = 2.13; 95% confidence interval (CI): 1.03–4.38; p = 0.04), history of illicit drug use (OR = 3.57; CI: 1.78–7.13; p &lt; 0.001), and history of marijuana use (OR = 7.05; CI: 3.85–12.91; p &lt; 0.001) were independent predictors of an aberrant UDT finding. Conclusion: Despite limitations of immunoassay UDT, it was able to detect aberrant drug-taking behaviors in a significant number of patients seen at a safety-net hospital palliative care clinic, including cocaine use. These findings support universal UDT monitoring and utility of immunoassay-based UDT in resource-limited settings.

Face validity and reliability test of the Danish version of the compliance questionnaire rheumatology in patients with early rheumatoid arthritis

BackgroundSupporting adherence to medication is an essential part of the treatment and care of patients with rheumatic and musculoskeletal diseases. The Compliance Questionnaire Rheumatology (CQR) measures adherence in rheumatic diseases through 19 items covering drug-taking behaviour to identify the reasons for adhering to treatment and the factors that contribute to suboptimal adherence. The objective of this study was to present the translation of the CQR into Danish and the face validity and reliability test.MethodsThe CQR was translated into Danish according to international guidelines, followed by a face validity test among 10 patients with rheumatoid arthritis in 2009. The test–retest reliability of the Danish CQR was evaluated in 49 patients with rheumatoid arthritis in 2020 - 2021 using the standard error of the measurement (SEM) converted into the minimally detectable change (MDC) and the intraclass correlation coefficient (ICC). Questionnaires were administered with a minimum of 10 days between assessments.ResultsThe participants in the reliability test had a mean age of 57.4 years (SD 16.1) and a mean disease duration of 1.13 years (range 2 months–2 years). The mean CQR score in the test and retest was 62.7 (confidence interval (CI) 58.8; 66.6) and 62.5 (CI 58.9; 66.1), respectively, with a SEM of 8.59 (7.16; 10.73) and an MDC of 16.83. A satisfactory test–retest reliability was confirmed by an ICC value of 0.79 (CI 0.68; 0.89).ConclusionThe Danish CQR has satisfactory test–retest reliability in patients newly diagnosed with rheumatoid arthritis and is considered a reliable tool to measure adherence in this group.

Olfactory Bulbectomy Model of Depression Lowers Responding for Food in Male and Female Rats: The Modulating Role of Caloric Restriction and Response Requirement.

Depression is a psychiatric disorder characterized by a marked decrease in reward sensitivity. By using the olfactory bulbectomy (OBX) model of depression, it was shown that OBX rats display enhanced drug-taking and seeking behaviors in a self-administration paradigm than sham-operated (SHAM) controls, and sex is an important regulating factor. To reveal potential strain effects, we compared the operant behavior of male and female Sprague-Dawley and Wistar OBX and SHAM rats trained to self-administer palatable food pellets. Results showed that Sprague-Dawley OBX rats of both sexes exhibited lower operant responding rates and food intake than SHAM controls. Food restriction increased responding in both OBX and SHAM groups. Female rats responded more than males, but the OBX lesion abolished this effect. In Wistar rats, bulbectomy lowered food self-administration only during the last training days. Food self-administration was not significantly affected in Wistar rats by sex. In summary, this study showed that bulbectomy significantly reduces operant responding and food intake in male and female Sprague-Dawley rats while inducing a mild reducing effect only in the Wistar strain. Strain-dependent effects were also observed in the modulating role of sex and food restriction on operant responding and palatable food intake.

Operant novelty seeking predicts cue-induced reinstatement following cocaine but not water reinforcement in male rats.

An important facet of cocaine addiction is a high propensity to relapse, with increasing research investigating factors that predispose individuals toward uncontrolled drug use and relapse. A personality trait linked to drug addiction is high sensation seeking, i.e., a preference for novel sensations/experiences. In an animal model of sensation seeking, operant novelty seeking predicts the acquisition of drug self-administration. The primary goal of this research was to evaluate the hypothesis that sensitivity to the reinforcing effects of novel sensory stimuli predicts more intensive aspects of drug-taking behaviors, such as relapse. Rats were first tested for Operant Novelty Seeking, during which responses resulted in complex visual/auditory stimuli. Next, rats were trained to respond to water/cocaine reinforcers signaled by a cue light. Finally, rats were exposed to extinction in the absence of discrete cues and subsequently tested in a single session of cue-induced reinstatement, during which active responses resulted in cues previously paired with water/cocaine delivery. The present study showed operant responses to produce novel sensory stimuli positively correlate with responding for cocaine during self-administration and during discrete cue-induced reinstatement, but no association with performance during extinction. A different pattern of associations was observed for a natural reward, in this case, water reinforcement. Here, the degree of novelty seeking also correlated with responding to water reinforcement and extinction responding; however, operant novelty seeking did not correlate with responding to water cues during testing of cue-induced reinstatement. Taken together, the incongruence of relationships indicates an underlying difference between natural and drug reinforcers. In summary, we found a reinforcer-dependent relationship between operant novelty seeking (i.e., sensation seeking) and responsivity to extinction and discrete cues signaling availability for cocaine (i.e., craving), demonstrating the validity of the operant novelty seeking model to investigate drug seeking and relapse.

Exploring Drug &amp; Substance Abuse Implications 2023

Background: An estimated 19.5 million people aged 12 or older in the United States have had a substance use disorder related to illicit drugs or alcohol in 2020 (Hoenig, 2020). Drug addiction is a chronic and relapsing brain disorder characterized by compulsive drug-seeking and drug-taking behaviors. The primary causes of which include interrelated brain networks that comprise the reward and anti-reward system, as well as the central immune system. While its validity as a disease is controversial, many attribute its existence to moral failing and personal choice. As such, it remains a complex phenomenon that alters the brain function and leads to a plethora of psychological and neurological changes, temporary and permanent. Interestingly, there are several factors that contribute to an individual’s vulnerability to drug addiction, the most surprising of which is genetic predispositions, environmental factors, early drug introductions and everything in between. Drug abuse remains a critical global issue that has severe implications for public health and societal well-being. Aims: By shedding light on their addictive properties and the resulting physiological and psychological consequences this article aims to raise awareness about the dangers associated with these substances. Furthermore, this article investigates the significant risks that come hand in hand with drug abuse. In addition to examining the causes and risks of drug abuse, it delves into preventive measures as well as treatment approaches. Evidence based strategies such as education programs, early intervention initiatives, harm reduction practices and policy measures are essential in reducing both the prevalence and harmful effects of drug abuse. Moreover, exploring various treatment modalities ranging from pharmacological interventions to behavioral therapies - It emphasizes the importance of personalized, comprehensive and multidisciplinary approaches when it comes to tackling drug addiction. .....

Role of social context in addiction etiology and recovery

While social context has long been considered central to substance use disorder prevention and treatment and many drug-taking events occur in social settings, experimental research on social context has historically been limited. Recent years have seen an emergence of concerted preclinical and human laboratory research documenting the direct impact of social context on substance use, delineating behavioral and neurobiological mechanisms underlying social influence's role. We review this emerging preclinical and human laboratory literature from a theoretical lens that considers distinct stages of the addiction process including drug initiation/acquisition, escalation, and recovery. A key conclusion of existing research is that the impact of the social environment is critically moderated by the drug-taking behavior and drug use history of a social peer. Specifically, while drug-free social contexts can reduce the likelihood of drug use initiation and act as a competitive non-drug alternative preventing escalation, drug-using peers can equally facilitate initiation and escalation through peer modeling as a contingent reward of use. Likewise, social context may facilitate recovery or serve as a barrier that increases the chances of a return to regular use. We conclude by discussing evidence-based treatments and recovery support services that explicitly target social mechanisms or that have identified social context as a mechanism of change within treatment. Ultimately, new areas for research including the expansion of drug classes studied and novel human laboratory designs are needed to further translate emerging findings into clinical practice.

Paternal morphine exposure in rats reduces social play in adolescent male progeny without affecting drug-taking behavior in juvenile males or female offspring

The ongoing opioid addiction crisis necessitates the identification of novel risk factors to improve prevention and treatment of opioid use disorder. Parental opioid exposure has recently emerged as a potential regulator of offspring vulnerability to opioid misuse, in addition to heritable genetic liability. An understudied aspect of this “missing heritability” is the developmental presentation of these cross-generational phenotypes. This is an especially relevant question in the context of inherited addiction-related phenotypes, given the prominent role of developmental processes in the etiology of psychiatric disorders. Paternal morphine self-administration was previously shown to alter the sensitivity to the reinforcing and antinociceptive properties of opioids in the next generation. Here, phenotyping was expanded to include the adolescent period, with a focus on endophenotypes related to opioid use disorders and pain. Paternal morphine exposure did not alter heroin or cocaine self-administration in male and female juvenile progeny. Further, baseline sensory reflexes related to pain were unaltered in morphine-sired adolescent rats of either sex. However, morphine-sired adolescent males exhibited a reduction in social play behavior. Our findings suggest that, in morphine-sired male offspring, paternal opioid exposure does not affect opioid intake during adolescence, suggesting that this phenotype does not emerge until later in life. Altered social behaviors in male morphine-sired adolescents indicate that the changes in drug-taking behavior in adults sired by morphine-exposed sires may be due to more complex factors not yet fully assessed.