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

Daiwile, Atul P.; Jayanthi, Subramaniam; Cadet, Jean Lud

doi:10.1016/j.neubiorev.2022.104674

Cited by 37 publications

(33 citation statements)

References 190 publications

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“…One of the limitations has to do with our use of only male rats in the present study. The accumulated evidence indicates that there exist sex-dependent differences in the behavioral and molecular consequences of METH self-administration (Daiwile et al, 2021(Daiwile et al, , 2022a. Although many studies use male rodents to investigate molecular and biochemical mechanisms of substance use disorders (SUDs), the evidence is clear that there exist sex differences in the clinical courses and responses to therapies in those populations (McHugh et al, 2018(McHugh et al, , 2021.…”

Section: Discussionmentioning

confidence: 99%

“…These ideas were supported by the work of Daiwile et al (2022b) that had documented baseline differences in stress-related genes (2021) and in markers of dopaminergic systems in some brain regions. Daiwile et al (2022a) have reviewed these issues in great length in the case of METH, and previous studies from our laboratory have investigated sex differences in some genes (Daiwile et al, 2021). Future studies have already been planned for us to measure regional and more global transcriptional responses in rats of both sexes.…”

Section: Discussionmentioning

confidence: 99%

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

Munoz

Jayanthi²,

Ladenheim³

et al. 2023

Front. Mol. Neurosci.

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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. Recent studies have reported that about 50% of METH users develop MUD, suggesting that there may be differential molecular effects of METH between the brains of individuals who met criteria for addiction and those who did not after being exposed to the drug. The present study aimed at identifying potential transcriptional differences between compulsive and non-compulsive METH self-administering male rats by measuring global gene expression changes in the hippocampus using RNA sequencing. Herein, we used a model of METH self-administration (SA) accompanied by contingent foot-shock punishment. This approach led to the separation of animals into shock-resistant rats (compulsive) that continued to take METH and shock-sensitive rats (non-compulsive) that suppressed their METH intake in the presence of punished METH taking. Rats were euthanized 2 h after the last METH SA plus foot-shock session. Their hippocampi were immediately removed, frozen, and used later for RNA sequencing and qRT-PCR analyses. RNA sequencing analyses revealed differential expression of mRNAs encoding cell adhesion molecules (CAMs) between the two rat phenotypes. qRT-PCR analyses showed significant higher levels of Cdh1, Glycam1, and Mpzl2 mRNAs in the compulsive rats in comparison to non-compulsive rats. The present results implicate altered CAM expression in the hippocampus in the behavioral manifestations of continuous compulsive METH taking in the presence of adverse consequences. Our results raise the novel possibility that altered CAM expression might play a role in compulsive METH taking and the cognitive impairments observed in MUD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Munoz

Jayanthi²,

Ladenheim³

et al. 2023

Front. Mol. Neurosci.

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“…We focused separately on each of these four mutually exclusive major drug categories, because they are involved in a large number of overdoses in the United States, and because of their different pharmacological and pathophysiological effects [3,4,24,99,100]. Analogous examination for other drug categories would also be valuable, for example prescription opioids [6].…”

Section: Limitationsmentioning

confidence: 99%

“…Opioid or psychostimulant use disorders can have long-term trajectories over the lifespan [19,58-60], and sex differences in overdose vulnerability may change through adolescence, adulthood and menopause or aging, potentially depending on multiple underlying mechanisms [12,24,35]. Also, men and women could differ in their risk of overdose mortality based in part on gendered factors that may also change over the lifespan, such as family and social interactions and related trauma [61,62], risky behaviors (e.g., injecting alone) [63], and interaction with healthcare systems [64-69].…”

Section: Introductionmentioning

confidence: 99%

“…As indicated by an extensive recent review of preclinical and clinical data, sex differences in vulnerability to withdrawal and relapse-like behaviors for MOP-r agonists or psychostimulants were also not robust overall, particularly in humans [11]. However, given methodological and ethical reasons, experimental investigations do not typically examine overdoses directly [8,11,24].…”

Section: Introductionmentioning

confidence: 99%

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Overdose mortality rates for opioids or stimulants are higher in males than females, controlling for rates of drug misuse: State-level data

Butelman¹,

Huang²,

Goldstein³

et al. 2023

Preprint

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Drug overdoses are an escalating cause of mortality in the United States, with potential sex differences across the lifespan. The objective of this study was to use state-level nationally representative data that includes the COVID-19 pandemic period to determine overdose mortality for specific drug categories across the lifespan of men and women. We used Centers for Disease Control and Prevention (CDC) Multiple Cause of Death 2020-2021 data on overdose mortality, for 50 states and District of Columbia, across 10-year age bins (age range: 15-74). The outcome measure was sex-specific crude overdose death rate (per 100,000) for: synthetic opioids excluding methadone (ICD-10 code: T40.4; e.g., fentanyl), heroin (T40.1), psychostimulants with abuse potential (T43.6; e.g., methamphetamine), and cocaine (T40.5). Multiple regression analyses adjusted for ethnic-cultural background and household net worth from Census data, and sex-specific rate of misuse of the relevant substances, from the National Survey on Drug Use and Health (2019-2020). For each of these major drug categories, men had greater overall overdose mortality than women. Although overall rates of mortality differed across jurisdictions, the sex ratio of mortality for each drug category was relatively stable (≈2- to 3-fold greater mortality in men vs women). These findings survived adjustment for state-level ethnic-cultural and economic variables, and for sex-specific misuse of each drug type (especially in the 25-34, 35-44, 45-54 and 55-64 age bins). These findings underscore the need for research into sex- and gender-based mechanisms underlying differential vulnerability in overdose mortality for these drugs, based on their diverse pharmacodynamics and pathophysiology.

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Sex-Dependent Alterations in the mRNA Expression of Enzymes Involved in Dopamine Synthesis and Breakdown After Methamphetamine Self-Administration

2022

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

Cited by 37 publications

References 190 publications

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

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

Overdose mortality rates for opioids or stimulants are higher in males than females, controlling for rates of drug misuse: State-level data

Sex-Dependent Alterations in the mRNA Expression of Enzymes Involved in Dopamine Synthesis and Breakdown After Methamphetamine Self-Administration

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