Incubation of methamphetamine craving in punishment-resistant individuals is associated with activation of specific gene networks in the rat dorsal striatum.

Methamphetamine use disorder (MUD) is characterized by loss of control over compulsive drug use. Here, we used a self-administration (SA) model to investigate transcriptional changes associated with the development of early and late compulsivity during contingent footshocks. Punishment initially separated methamphetamine taking rats into always shock-resistant (ASR) rats that continued active lever pressing and shock-sensitive (SS) rats that reduced their lever pressing.

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules.

Methamphetamine (METH) is a popular but harmful psychostimulant. METH use disorder (MUD) is characterized by compulsive and continued use despite adverse life consequences. METH users experience impairments in learning and memory functions that are thought to be secondary to METH-induced abnormalities in the hippocampus.

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

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.

Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration.

Methamphetamine (METH) use disorder affects both sexes, with sex differences occurring in behavioral, structural, and biochemical consequences. The molecular mechanisms underlying these differences are unclear. Herein, we used a rat model to identify potential sex differences in the effects of METH on brain dopaminergic systems.

Sex differences in methamphetamine use disorder perused from pre-clinical and clinical studies: Potential therapeutic impacts.

Methamphetamine (METH) use, and misuse are associated with severe socioeconomic consequences. METH users develop tolerance, lose control over drug taking behaviors, and suffer frequent relapses even during treatment. The clinical course of METH use disorder is influenced by multifactorial METH-induced effects on the central and peripheral nervous systems.

Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2).

Methamphetamine (METH) use disorder (MUD) is characterized by compulsive and repeated drug taking despite negative life consequences. Large intake of METH in humans and animals is accompanied by dysfunctions in learning and memory processes. The endocannabinoid system (ECS) is known to modulate synaptic plasticity and cognitive functions.

Epigenetic Regulatory Dynamics in Models of Methamphetamine-Use Disorder.

Methamphetamine (METH)-use disorder (MUD) is a very serious, potentially lethal, biopsychosocial disease. Exposure to METH causes long-term changes to brain regions involved in reward processing and motivation, leading vulnerable individuals to engage in pathological drug-seeking and drug-taking behavior that can remain a lifelong struggle. It is crucial to elucidate underlying mechanisms by which exposure to METH leads to molecular neuroadaptive changes at transcriptional and translational levels.

Neurotoxicity of methamphetamine: Main effects and mechanisms.

Methamphetamine (METH) is an illicit psychostimulant that is abused throughout the world. METH addiction is also a major public health concern and the abuse of large doses of the drug is often associated with serious neuropsychiatric consequences that may include agitation, anxiety, hallucinations, paranoia, and psychosis. Some human methamphetamine users can also suffer from attention, memory, and executive deficits.

Epigenetic Landscape of Methamphetamine Use Disorder.

The persistence of the addiction phenotype in methamphetamine use disorder (MUD) suggests the potential presence of epigenetic changes and potential structural adaptations that may drive the manifestations of MUD in humans. In the present review, we discuss the evidence that documents the fact that methamphetamine exposure can cause changes in epigenetic modifications, including histone acetylation and methylation, as well as DNA methylation and hydroxymethylation in a complex manner that need to be fully dissected. Nevertheless, our work has demonstrated the existence of correlations between behavioral changes and epigenetic alterations during methamphetamine selfadministration.

Epigenetics of addiction.

Substance use disorders are complex biopsychosocial disorders that have substantial negative neurocognitive impact in various patient populations. These diseases involve the compulsive use of licit or illicit substances despite adverse medicolegal consequences and appear to be secondary to long-lasting epigenetic and transcriptional adaptations in brain reward and non-reward circuits. The accumulated evidence supports the notion that repeated drug use causes changes in post-translational histone modifications and in DNA methylation/hydroxymethylation processes in several brain regions.

Potassium Channels and Their Potential Roles in Substance Use Disorders.

Substance use disorders (SUDs) are ubiquitous throughout the world. However, much remains to be done to develop pharmacotherapies that are very efficacious because the focus has been mostly on using dopaminergic agents or opioid agonists. Herein we discuss the potential of using potassium channel activators in SUD treatment because evidence has accumulated to support a role of these channels in the effects of rewarding drugs.

Sex- and Brain Region-specific Changes in Gene Expression in Male and Female Rats as Consequences of Methamphetamine Self-administration and Abstinence.

Sex differences in METH use exist among human METH users and in animal models of METH addiction. Herein, we tried to identify potential differences in gene expression between female and male rats after Methamphetamine self-administration (METH SA). Rats were trained to self-administer METH using two 3-hours daily sessions for 20 days.

Methamphetamine pre-exposure induces steeper escalation of methamphetamine self-administration with consequent alterations in hippocampal glutamate AMPA receptor mRNAs.

Methamphetamine use disorder (MUD) is often modeled using rodent self-administration (SA) experiments. Noncontingent injections of a drug given to rodents before self-administration training can increase drug SA. In the present study, we injected methamphetamine before putting rats through methamphetamine SA to investigate SA escalation.

Compulsive methamphetamine taking induces autophagic and apoptotic markers in the rat dorsal striatum.

Methamphetamine (METH) use disorder (MUD) is often accompanied by psychotic symptoms, cognitive deficits, and pathological changes in the brains of users. Animals that experimenters injected with drugs also show neurodegenerative changes in their brains. Recently, we have been investigating METH-induced molecular and biochemical consequences in animals that had infused themselves with METH using the drug self-administration (SA) paradigm.

Neurochemical and behavioral comparisons of contingent and non-contingent methamphetamine exposure following binge or yoked long-access self-administration paradigms.

Rationale: Abuse of the psychostimulant methamphetamine (METH) can cause long-lasting damage to brain monoaminergic systems and is associated with profound mental health problems for users, including lasting cognitive impairments. Animal models of METH exposure have been useful in dissecting the molecular effects of the drug on cognition, but many studies use acute, non-contingent "binge" administrations of METH which do not adequately approximate human METH use. Long-term METH exposure via long-access (LgA) self-administration paradigms has been proposed to more closely reflect human use and induce cognitive impairments.

A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens.

The transition from occasional to escalated psychostimulant use is accelerated by prior drug exposure. These behavioral observations may be related to long-lasting transcriptional and/or epigenetic changes induced by the drug pre-exposure. Herein, we investigated if a single methamphetamine (METH) injection would enhance METH self-administration (SA) and impact any METH SA-induced epigenetic or transcriptional alterations.

Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking.

Background: Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown.

HDAC superfamily promoters acetylation is differentially regulated by modafinil and methamphetamine in the mouse medial prefrontal cortex.

Dysregulation of histone deacetylases (HDAC) has been proposed as a potential contributor to aberrant transcriptional profiles that can lead to changes in cognitive functions. It is known that METH negatively impacts the prefrontal cortex (PFC) leading to cognitive decline and addiction whereas modafinil enhances cognition and has a low abuse liability. We investigated if modafinil (90 mg/kg) and methamphetmine (METH) (1 mg/kg) may differentially influence the acetylation status of histones 3 and 4 (H3ac and H4ac) at proximal promoters of class I, II, III, and IV HDACs.

Compulsive methamphetamine taking and abstinence in the presence of adverse consequences: Epigenetic and transcriptional consequences in the rat brain.

Methamphetamine addiction is characterized by compulsive binges of drug intake despite adverse life consequences. A model of methamphetamine self-administration that includes contingent footshocks to constitute adverse consequences has helped to segregate rats that reduce or stop lever pressing for methamphetamine (sensitive) from those that continue to lever press for the drug (resistant) in the presence of negative outcomes. We have observed differential DNA hydroxymethylation and increased expression of potassium channel mRNAs in the nucleus accumbens of sensitive compared to resistant rats, suggesting a role of these channels in suppressing methamphetamine intake.

Genetic and Environmental Risk Factors for Cannabis Use: Preliminary Results for the Role of Parental Care Perception.

Background: Vulnerability to cannabis use (CU) initiation and problematic use have been shown to be affected by both genetic and environmental factors, with still inconclusive and uncertain evidence.

Objective: Aim of the present study was to investigate the possible interplay between gene polymorphisms and psychosocial conditions in CU susceptibility.

Methods: Ninety-two cannabis users and ninety-three controls have been included in the study.

Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration.

Repeated exposure to the opioid agonist, oxycodone, can lead to addiction. Here, we sought to identify potential neurobiological consequences of withdrawal from escalated and non-escalated oxycodone self-administration in rats. To reach these goals, we used short-access (ShA) (3 h) and long-access (LgA) (9 h) exposure to oxycodone self-administration followed by protracted forced abstinence.

The effects of single-dose injections of modafinil and methamphetamine on epigenetic and functional markers in the mouse medial prefrontal cortex: potential role of dopamine receptors.

METH use causes neuroadaptations that negatively impact the prefrontal cortex (PFC) leading to addiction and associated cognitive decline in animals and humans. In contrast, modafinil enhances cognition by increasing PFC function. Accumulated evidence indicates that psychostimulant drugs, including modafinil and METH, regulate gene expression via epigenetic modifications.

Gene variants and educational attainment in cannabis use: mediating role of DNA methylation.

Genetic and sociodemographic risk factors potentially associated with cannabis use (CU) were investigated in 40 cannabis users and 96 control subjects. DNA methylation analyses were also performed to explore the possibility of epigenetic changes related to CU. We conducted a candidate gene association study that included variants involved in the dopaminergic (ANKK1, NCAM1 genes) and endocannabinoid (CNR1, CNR2 gene) pathways.

Repeated methamphetamine and modafinil induce differential cognitive effects and specific histone acetylation and DNA methylation profiles in the mouse medial prefrontal cortex.

Methamphetamine (METH) and modafinil are psychostimulants with different long-term cognitive profiles: METH is addictive and leads to cognitive decline, whereas modafinil has little abuse liability and is a cognitive enhancer. Increasing evidence implicates epigenetic mechanisms of gene regulation behind the lasting changes that drugs of abuse and other psychotropic compounds induce in the brain, like the control of gene expression by histones 3 and 4 tails acetylation (H3ac and H4ac) and DNA cytosine methylation (5-mC). Mice were treated with a seven-day repeated METH, modafinil or vehicle protocol and evaluated in the novel object recognition (NOR) test or sacrificed 4days after last injection for molecular assays.

Selective Activation of Striatal NGF-TrkA/p75NTR/MAPK Intracellular Signaling in Rats That Show Suppression of Methamphetamine Intake 30 Days following Drug Abstinence.

Background: The continuing epidemic of methamphetamine addiction has prompted research aimed at understanding striatal dysfunctions potentially associated with long-term methamphetamine use.

Methods: Here, we investigated transcriptional and translational alterations in the expression of neurotrophic factors in the rat striatum at 30 days following methamphetamine self-administration and footshock punishment. Male Sprague-Dawley rats were trained to self-administer methamphetamine (0.