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Molecular Mechanisms Associated with Drug Addiction Vulnerability

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 6685

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Special Issue Editor

Dr. Jorge Manzanares

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Guest Editor

Instituto de Neurociencias, Miguel Hernández University, Av. Ramón y Cajal s/n, 03550 San Juan de Alicante, Alicante, Spain
Interests: cannabinoids; drug addiction; alcohol; animal model; biomarkers; psychiatry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

"Molecular Mechanisms Associated with Drug Addiction Vulnerability" is a Special Issue highlighting advances in research on the molecular, genetic, and epigenetic mechanisms involved in addiction to unify concepts and identify new targets to improve the diagnosis and treatment of addiction in humans.

It is widely known that drug use causes many deaths each year, separates families, and paralyzes the health care system. The development of drug dependence is a multifactorial disease involving a complex interaction between genes and the environment. The abuse of drugs produces molecular alterations in the brain's reward circuitry, particularly in the mesolimbic dopaminergic system. These changes alter neuroplasticity and its activity, leading to abnormal behaviors in vulnerable individuals over time. In addition, life experience can shape the epigenetic landscape of the brain and thus contribute to an individual's vulnerability to drug use. Substance use disorders are frequent in patients with psychiatric diseases such as anxiety, depression, bipolar disorder, or posttraumatic stress disorder. This may occur because genetic determinants make these patients more vulnerable to substance use. For instance, adolescent substance use may increase the risk of developing a later substance abuse disorder and serves as an additional risk factor for onset psychiatric symptoms. On the other hand, perinatal drug exposure affects infant development, where the neural molecular mechanisms that mediate social and reward behaviors and stress reactivity are affected and may also be involved in developing an offspring's vulnerability to addiction.

In summary, all the fundamental aspects that can lead an individual to compulsive substance use, environmental and perinatal factors, psychiatric diseases affecting neurodevelopment and neuroplasticity, and the molecular mechanisms of addiction will be analyzed in this Special Issue.

Dr. Jorge Manzanares
Guest Editor

Dr. Ani Gasparyan and Dr. Daniela Navarro
Special Assistants

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

drug addiction
molecular mechanisms
genetics
epigenetics
perinatal exposure
psychiatric diseases

Published Papers (3 papers)

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Research

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15 pages, 2664 KiB

Open AccessArticle

Mechanical Stimulation Alters Chronic Ethanol-Induced Changes to VTA GABA Neurons, NAc DA Release and Measures of Withdrawal

by Kyle B. Bills, Dallin Z. Otteson, Gavin C. Jones, James N. Brundage, Emily K. Baldwin, Christina A. Small, Hee Young Kim, Jordan T. Yorgason, Jonathan D. Blotter and Scott C. Steffensen

Int. J. Mol. Sci. 2022, 23(20), 12630; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012630 - 20 Oct 2022

Cited by 1 | Viewed by 1490

Abstract

Therapeutic activation of mechanoreceptors (MStim) in osteopathy, chiropractic and acupuncture has been in use for hundreds of years with a myriad of positive outcomes. It has been previously shown to modulate the firing rate of neurons in the ventral tegmental area (VTA) and dopamine (DA) release in the nucleus accumbens (NAc), an area of interest in alcohol-use disorder (AUD). In this study, we examined the effects of MStim on VTA GABA neuron firing rate, DA release in the NAc, and behavior during withdrawal from chronic EtOH exposure in a rat model. We demonstrate that concurrent administration of MStim and EtOH significantly reduced adaptations in VTA GABA neurons and DA release in response to a reinstatement dose of EtOH (2.5 g/kg). Behavioral indices of EtOH withdrawal (rearing, open-field crosses, tail stiffness, gait, and anxiety) were substantively ameliorated with concurrent application of MStim. Additionally, MStim significantly increased the overall frequency of ultrasonic vocalizations, suggesting an increased positive affective state. Full article

(This article belongs to the Special Issue Molecular Mechanisms Associated with Drug Addiction Vulnerability)

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20 pages, 3416 KiB

Open AccessArticle

Biochemical Neuroadaptations in the Rat Striatal Dopaminergic System after Prolonged Exposure to Methamphetamine Self-Administration

by Subramaniam Jayanthi, Bruce Ladenheim, Patricia Sullivan, Michael T. McCoy, Irina N. Krasnova, David S. Goldstein and Jean Lud Cadet

Int. J. Mol. Sci. 2022, 23(17), 10092; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231710092 - 03 Sep 2022

Cited by 5 | Viewed by 1958

Abstract

Perturbations in striatal dopamine (DA) homeostasis might underlie the behavioral and pathobiological consequences of METH use disorder in humans. To identify potential consequences of long-term METH exposure, we modeled the adverse consequence DSM criterion of substance use disorders by giving footshocks to rats that had escalated their intake of METH during a drug self-administration procedure. Next, DA D1 receptor antagonist, SCH23390 was injected. Thereafter, rats were euthanized to measure several indices of the striatal dopaminergic system. Footshocks split the METH rats into two phenotypes: (i) shock-sensitive that decreased their METH-intake and (ii) shock-resistant that continued their METH intake. SCH23390 caused substantial dose-dependent reduction of METH taking in both groups. Stopping SCH23390 caused re-emergence of compulsive METH taking in shock-resistant rats. Compulsive METH takers also exhibited greater incubation of METH seeking than non-compulsive rats during withdrawal from METH SA. Analyses of DA metabolism revealed non-significant decreases (about 35%) in DA levels in resistant and sensitive rats. However, striatal contents of the deaminated metabolites, DOPAL and DOPAC, were significantly increased in sensitive rats. VMAT2 and DAT protein levels were decreased in both phenotypes. Moreover, protein expression levels of the D1-like DA receptor, D5R, and D2-like DA receptors, D3R and D4R, were significantly decreased in the compulsive METH takers. Our results parallel findings in post-mortem striatal tissues of human METH users who develop Parkinsonism after long-term METH intake and support the use of this model to investigate potential therapeutic interventions for METH use disorder. Full article

(This article belongs to the Special Issue Molecular Mechanisms Associated with Drug Addiction Vulnerability)

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Review

Jump to: Research

18 pages, 717 KiB

Open AccessReview

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

by María Salud García-Gutiérrez, Francisco Navarrete, Ani Gasparyan, Daniela Navarro, Álvaro Morcuende, Teresa Femenía and Jorge Manzanares

Int. J. Mol. Sci. 2022, 23(11), 5908; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23115908 - 25 May 2022

Cited by 5 | Viewed by 2679

Abstract

Cumulative evidence has pointed out cannabinoid CB2 receptors (CB₂r) as a potential therapeutic key target for treating alcohol use disorder (AUD). This review provides the most relevant results obtained from rodent and human studies, including an integrative section focused on the involvement of CB₂r in the neurobiology of alcohol addiction. A literature search was conducted using the electronic databases Medline and Scopus for articles. The search strategy was as follows: “Receptor, Cannabinoid, CB2” AND “Alcohol-Related Disorders” AND “human/or patients”; “Receptor, Cannabinoid, CB2” AND “Alcohol” OR “Ethanol” AND “rodents/or mice/or rats”. Pharmacological approaches demonstrated that the activation or blockade of CB₂r modulated different alcohol-addictive behaviors. Rodent models of alcoholism revealed significant alterations of CB₂r in brain areas of the reward system. In addition, mice lacking CB₂r (CB₂KO) show increased alcohol consumption, motivation, and relapse alterations. It has been stressed that the potential neurobiological mechanisms underlying their behavioral effects involve critical elements of the alcohol reward system. Interestingly, recent postmortem studies showed CNR2 alterations in brain areas of alcoholic patients. Moreover, although the number of studies is limited, the results revealed an association between some genetic alterations of the CNR2 and an increased risk for developing AUD. This review provides evidence that CB₂r may play a role in alcohol addiction. Clinical studies are necessary to figure out whether CB₂r ligands may prove useful for the treatment of AUD in humans. Full article

(This article belongs to the Special Issue Molecular Mechanisms Associated with Drug Addiction Vulnerability)

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