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Handbook of Experimental Pharmacology 2020Substance use disorders represent a global public health issue. This mental health disorder is hypothesized to result from neurobiological changes as a result of chronic... (Review)
Review
Substance use disorders represent a global public health issue. This mental health disorder is hypothesized to result from neurobiological changes as a result of chronic drug exposure and clinically manifests as inappropriate behavioral allocation toward the procurement and use of the abused substance and away from other behaviors maintained by more adaptive nondrug reinforcers (e.g., social relationships, work). The dynorphin/kappa-opioid receptor (KOR) is one receptor system that has been altered following chronic exposure to drugs of abuse (e.g., cocaine, opioids, alcohol) in both laboratory animals and humans, implicating the dynorphin/KOR system in the expression, mechanisms, and treatment of substance use disorders. KOR antagonists have reduced drug self-administration in laboratory animals under certain experimental conditions, but not others. Recently, several human laboratory and clinical trials have evaluated the effectiveness of KOR antagonists as candidate pharmacotherapies for cocaine or tobacco use disorder to test hypotheses generated from preclinical studies. KOR antagonists failed to significantly alter drug use metrics in humans suggesting translational discordance between some preclinical drug self-administration studies and consistent with other preclinical drug self-administration studies that provide concurrent access to an alternative nondrug reinforcer (e.g., food). The implications of this translational discordance and future directions for examining the therapeutic potential of KOR agonists or antagonists as candidate substance use disorder pharmacotherapies are discussed.
Topics: Animals; Dynorphins; Humans; Receptors, Opioid, kappa; Substance-Related Disorders
PubMed: 31463605
DOI: 10.1007/164_2019_268 -
Neuroscience Letters May 2021Various research studies that have investigated the association between HIV infection and addiction underpin the role of various drugs of abuse in impairing... (Review)
Review
Various research studies that have investigated the association between HIV infection and addiction underpin the role of various drugs of abuse in impairing immunological and non-immunological pathways of the host system, ultimately leading to augmentation of HIV infection and disease progression. These studies have included both in vitro and in vivo animal models wherein investigators have assessed the effects of various drugs on several disease parameters to decipher the impact of drugs on both HIV infection and progression of HIV-associated neurocognitive disorders (HAND). However, given the inherent limitations in the existing animal models of HAND, these investigations only recapitulated specific aspects of the disease but not the complex human syndrome. Despite the inability of HIV to infect rodents over the last 30 years, multiple strategies have been employed to develop several rodent models of HAND. While none of these models can accurately mimic the overall pathophysiology of HAND, they serve the purpose of modeling some unique aspects of HAND. This review provides an overview of various animal models used in the field and a careful evaluation of methodological strengths and limitations inherent in both the model systems and study designs to understand better how the various animal models complement one another.
Topics: Animals; Brain; Comorbidity; Disease Models, Animal; HIV Infections; HIV-1; Humans; Mice; Neurocognitive Disorders; Rats; Substance-Related Disorders
PubMed: 33794296
DOI: 10.1016/j.neulet.2021.135863 -
The European Journal of Neuroscience Aug 2019Drug addiction is an aberrant memory that shares the same memory processes as other memories. Brief exposure to drug-associated cues could result in reconsolidation, a... (Review)
Review
Drug addiction is an aberrant memory that shares the same memory processes as other memories. Brief exposure to drug-associated cues could result in reconsolidation, a hypothetical process during which original memory could be updated. In contrast, longer exposure times to drug-associated cues could trigger extinction, a process that decreases the conditioned responding. In this review, we discuss the pharmacological and non-pharmacological manipulations on the reconsolidation and extinction that could be used to interfere with drug reward memories. Pharmacological agents such as β-adrenergic receptor antagonist propranolol can interfere with reconsolidation to disrupt drug reward memory. Pharmacological agents such as the NMDA receptor glycine site agonists d-cycloserine and d-serine can facilitate extinction and then attenuate the expression of drug reward memory. Besides pharmacological interventions, drug-free behavioral approaches by utilizing the reconsolidation and extinction, such as 'post-retrieval extinction' and 'UCS-retrieval extinction', are also effective to erase or inhibit the recall of drug reward memory. Taken together, pharmacological modulation and non-pharmacological modulation of reconsolidation and extinction are promising approaches to regulate drug reward memory and prevent relapse.
Topics: Adrenergic beta-Antagonists; Animals; Conditioning, Classical; Extinction, Psychological; Humans; Memory; Mental Recall; Reward; Substance-Related Disorders
PubMed: 30113098
DOI: 10.1111/ejn.14072 -
Psychiatric Services (Washington, D.C.) Jun 2021
Topics: Child; Child Abuse; Child Custody; Child Welfare; Family; Humans; Parents; Pharmaceutical Preparations; Substance-Related Disorders
PubMed: 33167816
DOI: 10.1176/appi.ps.202000388 -
Behavioural Neurology 2022Drug use and abuse are complex issues in that the basis of each may involve different determinants and consequences, and the transition from one to the other may be... (Review)
Review
Drug use and abuse are complex issues in that the basis of each may involve different determinants and consequences, and the transition from one to the other may be equally multifaceted. A recent model of the addiction cycle (as proposed by Koob and his colleagues) illustrates how drug-taking patterns transition from impulsive (acute use) to compulsive (chronic use) as a function of various neuroadaptations leading to the downregulation of DA systems, upregulation of stress systems, and the dysregulation of the prefrontal/orbitofrontal cortex. Although the nature of reinforcement in the initiation and mediation of these effects may differ (positive vs. negative), the role of reinforcement in drug intake (acute and chronic) is well characterized. However, drugs of abuse have other stimulus properties that may be important in their use and abuse. One such property is their aversive effects that limit drug intake instead of initiating and maintaining it. Evidence of such effects comes from both clinical and preclinical populations. In support of this position, the present review describes the aversive effects of drugs (assessed primarily in conditioned taste aversion learning), the fact that they occur concurrently with reward as assessed in combined taste aversion/place preference designs, the role of aversive effects in drug-taking (in balance with their rewarding effects), the dissociation of these affective properties in that they can be affected in different ways by the same manipulations, and the impact of various parametric, experiential, and subject factors on the aversive effects of drugs and the consequent impact of these factors on their use and abuse potential.
Topics: Humans; Reward; Substance-Related Disorders; Taste
PubMed: 35496768
DOI: 10.1155/2022/8634176 -
Emergencias : Revista de La Sociedad... Apr 2023Persons with HIV infection who use illicit drugs have higher morbidity and mortality rates than nonusers with or without HIV infection. The objetive were to detect...
OBJECTIVES
Persons with HIV infection who use illicit drugs have higher morbidity and mortality rates than nonusers with or without HIV infection. The objetive were to detect differences between acute poisoning from illicit drugs in patients with and without HIV infection who are attended in hospital emergency departments, and to identify independent factors associated with a worse prognosis, defined by hospital admission or death.
MATERIAL AND METHODS
Observational study in 2 hospitals between January 2017 and 31 December 2021. Included were patients with acute illicit drug poisoning with and without HIV infection.
RESULTS
Information for 1132 patients was included. The mean (SD) ages of patients with and without HIV infection, respectively, were 38.9 (9.6) years and 32.6 (10.4) years. In patients with HIV, the main drugs used were opioids (279 [85.3%]), cocaine (226 [69.1%]), and amphetamines (153 [46.8%]. None in this group were on methadone substitution therapy for opioid addiction. In patients without HIV infection the main drugs were cocaine (372 [47.2%]) and cannabis (238 [33.8%]). Alcohol was used along with illicit drugs in 387 cases. Multivariate analysis showed that the only variables independently associated with a poor prognosis were HIV infection (odds ratio [OR], 2.19 [1.29-3.11], P .003), age (OR, 1.20 [1.01-1.05], P .003), and acute poisoning from benzodiazepines (OR, 3.48 [2.14-5.66], P .001). The area under the receiver operating characteristic curve of the model was 0.717.
CONCLUSION
Certain characteristics distinguish the illicit drug use of patients with HIV infection. HIV infection, age, and the use of benzodiazepines are independently associated with a poor prognosis in acute poisonings.
Topics: Humans; Adult; HIV Infections; Substance-Related Disorders; Illicit Drugs; Cocaine; Benzodiazepines
PubMed: 37038940
DOI: No ID Found -
Progress in Neuro-psychopharmacology &... Jun 2020Drug abuse and brain disorders related to drug comsumption are public health problems with harmful individual and social consequences. The identification of therapeutic... (Review)
Review
Drug abuse and brain disorders related to drug comsumption are public health problems with harmful individual and social consequences. The identification of therapeutic targets and precise pharmacological treatments to these neuropsychiatric conditions associated with drug abuse are urgently needed. Understanding the link between neurobiological mechanisms and behavior is a key aspect of elucidating drug abuse-related targets. Due to various molecular, biochemical, pharmacological, and physiological features, the zebrafish (Danio rerio) has been considered a suitable vertebrate for modeling complex processes involved in drug abuse responses. In this review, we discuss how the zebrafish has been successfully used for modeling neurobehavioral phenotypes related to drug abuse and review the effects of opioids, cannabinoids, alcohol, nicotine, and psychedelic drugs on the central nervous system (CNS). Moreover, we summarize recent advances in zebrafish-based studies and outline potential advantages and limitations of the existing zebrafish models to explore the neurochemical bases of drug abuse and addiction. Finally, we discuss how the use of zebrafish models may present fruitful approaches to provide valuable clinically translatable data.
Topics: Analgesics, Opioid; Animals; Brain; Cannabinoids; Disease Models, Animal; Ethanol; Humans; Nicotine; Substance-Related Disorders; Zebrafish
PubMed: 31981718
DOI: 10.1016/j.pnpbp.2020.109873 -
Neuroscience and Biobehavioral Reviews Nov 2019Addiction is now recognized as a neurobiological and cognitive brain disorder and is generally viewed as a switch from recreational or voluntary to compulsive substance... (Review)
Review
Addiction is now recognized as a neurobiological and cognitive brain disorder and is generally viewed as a switch from recreational or voluntary to compulsive substance use despite aversive consequences. The habenula, composed of medial (MHb) and lateral (LHb) domains, has been implicated in regulating behavioral flexibility and anxiety-related behaviors and is considered a core component of the brain "anti-reward" system. These functions position the habenula to influence voluntary behaviors. Consistent with this view, emerging evidence points to alterations in habenula activity as important factors to contributing the loss of control over the use of drugs of abuse and the emergence of compulsive drug seeking behaviors. In this review, we will discuss the general functions of the MHb and LHb and describe how these functional properties allow this brain region to promote or suppress volitional behaviors. Then, we highlight mechanisms by which drugs of abuse may alter habenular activity, precipitating the emergence of addiction-relevant behavioral abnormalities.
Topics: Animals; Avoidance Learning; Compulsive Behavior; Habenula; Humans; Motivation; Reward; Self-Control; Substance-Related Disorders
PubMed: 29936111
DOI: 10.1016/j.neubiorev.2018.06.018 -
Current Neuropharmacology 2021Adolescence is the transitional period between childhood and adulthood and a critical period in brain development. Adolescence in humans is also associated with...
Adolescence is the transitional period between childhood and adulthood and a critical period in brain development. Adolescence in humans is also associated with increased expression of risk-taking behaviors. Epidemiological and clinical studies, for example, show a surge of drug abuse and raise the hypothesis that the adolescent brain undergoes critical changes resulting in diminished control. Determining how substance abuse during this critical period might cause longterm neurobiological changes in cognition and behavior is therefore critically important. The present work aims to provide an evaluation of the transgenerational and multi-generational phenotypes derived from parent animals exposed to drugs of abuse only during their adolescence. Specifically, we will consider changes found following the administration of cannabinoids, nicotine, alcohol and opiates. In addition, epigenetic modifications of the genome following drug exposure will be discussed as emerging evidence of the underlying adverse transgenerational effects. Notwithstanding, much of the new data discussed here is from animal models, indicating that future clinical studies are much needed to better understand the neurobiological consequences and mechanisms of drug actions on the human brains' development and maturation.
Topics: Adolescent; Adult; Animals; Cannabinoids; Child; Epigenesis, Genetic; Ethanol; Humans; Nicotine; Substance-Related Disorders
PubMed: 33655865
DOI: 10.2174/1570159X19666210303121519 -
Annals of Medicine Dec 2022Drug misuse is a global problem. Markets that supply illegal drugs often span international borders. However, each country has different primary drugs of use,... (Review)
Review
Drug misuse is a global problem. Markets that supply illegal drugs often span international borders. However, each country has different primary drugs of use, populations that are using and consequences of use. The policy approach of each country to addressing substance use disorders can be characterized along a continuum between purely public health approaches and purely law enforcement approaches. Historically, a law enforcement approach has been the primary strategy in much of the world. However, there is a growing movement towards use of a public health approach. This article provides four case examples, Ukraine, Philippines, Nigeria and Peru, where there is movement to develop addiction public health infrastructure. The work varies by country, but includes regulatory changes, workforce development and resource allocation all of which are supported by the United Nations Office on Drugs and Crime (UNODC) and multi-national organizations that provide training and technical assistance, funded primarily by the European Union and United States governments. All four countries highlighted have barriers to moving towards a more public health approach which may include popularity of the law enforcement approach, turbulent government environments, and economics of being a drug producing nation. However, whether starting from the top down with changed policies, such as Ukraine or from the bottom up with training community members as in the Philippines, each country provides an example of how donor resources can be applied to make the transition towards a more humane and evidence-based approach to addressing substance use disorders.Key MessagesWhile the primary approach to addressing drug use has focussed resources on law enforcement for over 100 years, many countries are adopting elements of a public health approach including prevention and treatment of the harms of drug use including substance use disorders.There is a growing global movement to make policy towards drugs and drug users more humane and evidence-based.Donor nation resources can be applied in a variety of combinations to improve care and outcomes for people who use drugs in low- and middle-income countries.
Topics: Humans; Nigeria; Public Health; Substance-Related Disorders
PubMed: 35792721
DOI: 10.1080/07853890.2022.2079150