The importance of examining sex differences in animal models validated to induce an addiction-like phenotype

Towers, Eleanor Blair; Lynch, Wendy J.

doi:10.1016/j.pbb.2021.173255

Cited by 9 publications

(5 citation statements)

References 59 publications

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“…A limitation of the present study was that sex differences were not investigated. Although sex differences for established psychostimulants such as methamphetamine and cocaine are well documented (Nicolas et al, 2022;Towers and Lynch, 2021), they are less established for synthetic cathinones and perhaps less common especially regarding drug intake (Marusich et al, 2021;Fattore et al, 2020). However, in the context of cytokines, recent evidence identi es important sex differences following abstinence from cathinone self-administration, with the primary differences being more robust elevation of brain cytokines in male rats and more pronounced elevation of plasma cytokines in female rats (Marusich et al, 2022).…”

Section: Al 2019)mentioning

confidence: 99%

Cyanidin prevents anxiety-like effects and dysregulation of cytokine systems during MDPV abstinence in rats

Inan

Meissler

Shekarabi

et al. 2022

Preprint

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Psychostimulant exposure and withdrawal cause neuroimmune dysregulation and anxiety that contributes to dependence and relapse. Here, we tested the hypothesis that abstinence from the synthetic cathinone MDPV (methylenedioxypyrovalerone) produces anxiety-like effects and enhanced levels of mesocorticolimbic cytokines that are inhibited by cyanidin, an anti-inflammatory flavonoid and nonselective blocker of IL-17A signaling. For comparison, we tested effects on glutamate transporter systems that are also dysregulated during psychostimulant abstinence. Rats injected for 9 d with MDPV (1 mg/kg, IP) or saline were pretreated daily with cyanidin (0.5 mg/kg, IP) or saline, followed by behavioral testing on the elevated zero maze (EZM) 72 h after the last MDPV injection. MDPV abstinence caused a reduction in time spent on the open arm of the EZM that was prevented by cyanidin. Cyanidin itself did not affect locomotor activity or time spent on the open arm, or cause aversive or rewarding effects in place preference experiments. MDPV abstinence caused enhancement of cytokine levels (IL-17A, IL-1β, IL-6, TNFα, IL-10, and CCL2) in the ventral tegmental area, but not amygdala, nucleus accumbens, or prefrontal cortex, that was prevented by cyanidin. During MDPV abstinence, mRNA levels of glutamate aspartate transporter (GLAST) and glutamate transporter subtype 1 (GLT-1) in the amygdala were also elevated but normalized by cyanidin treatment. These results show that MDPV abstinence causes withdrawal-induced anxiety, and brain-region specific dysregulation of cytokine and glutamate systems, that are both prevented by cyanidin, thus identifying cyanidin for further investigation in the context of psychostimulant dependence and relapse.

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Section: Al 2019)mentioning

confidence: 99%

Cyanidin prevents anxiety-like effects and dysregulation of cytokine systems during MDPV abstinence in rats

Inan

Meissler

Shekarabi

et al. 2022

Preprint

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show abstract

“…The lack of medications for CUD is largely due to candidate medications failing in clinical trials despite promising preclinical results. The challenge of failed translation is not unique to CUD research [ 2 ]; however, we argue that in order to produce a more representative and translationally relevant body of knowledge on the neurobiological basis and potential treatments for addiction, studies need to use animal models validated to induce addiction-like features like those observed in women and men with CUD and consider biological sex as a variable [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Extended-access (extended-access) drug self-administration procedures (i.e., ≥6-hr/day access to the drug) are the gold-standard for inducing addiction-like features in animals [ 3 , 4 ]. We use an intermittent, extended-access procedure (4 trials/hr; 24-hr/day for 10 days) that was developed to approximate the use patterns observed in humans (e.g., binge/abstinent patterns;[ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats

Towers,

Williams,

Aristidou

et al. 2024

Transl Psychiatry

Self Cite

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Relapse to drug use after abstinence is a major challenge in treating substance use disorder. Exposure to drug-associated cues during abstinence can trigger intense craving and precipitate relapse. New and more effective anti-relapse interventions are critically needed, particularly for cocaine use disorder since no effective pharmacological intervention is available. We discovered that a nutritional supplement we developed as part of a nutritional approach for managing patients with substance use disorder reduced patient reports of drug craving and relapse. The goal of this study was to determine the efficacy of this supplement, SMAASH-C, at reducing drug-craving/relapse vulnerability in males and females in rat models with cocaine. Effects were determined following extended-access cocaine self-administration (24-hr/day for 10 days) and a two-week treatment regimen at a moderate and moderate-to-high dose (0.4 and 0.8 g/kg/day) as well as a 6-week regimen at a moderate dose (0.4 g/kg/day; Experiment 2). We also determined its efficacy to offset serum markers of organ toxicity in response to chronic cocaine self-administration and abstinence (aspartate transaminase, alanine transaminase, amylase; urea nitrogen). In females, both the 2- and 6-week SMAASH-C treatment regimens reduced cocaine-seeking (extinction or cue-induced reinstatement), particularly when drug-seeking was heightened (e.g., during estrus). Despite a lack of efficacy to reduce drug-seeking in males, SMAASH-C treatment normalized cocaine/abstinence-induced increases in serum levels of aspartate transaminase and amylase, which are markers of liver and pancreatic toxicity respectively. Thus, the beneficial effects of oral SMAASH-C treatment over abstinence following chronic cocaine self-administration appears to be sex-specific.

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“…Cocaine use disorder is a chronic, relapsing disease that is prevalent in both males and females. However, sex differences in patterns of cocaine use and relapse vulnerability have been reported in both clinical and preclinical models [ 1 – 5 ]. In humans, female cocaine users report shorter periods of abstinence after initiating cocaine use [ 6 , 7 ], longer periods of cocaine use following relapse [ 8 ] and greater cocaine craving and depressive symptomatology [ 9 ] relative to men.…”

Section: Introductionmentioning

confidence: 99%

mGlu5 inhibition in the basolateral amygdala prevents estrous cycle-dependent changes in cue-induced cocaine seeking

Corbett

Miller

Loweth

2023

Addiction Neuroscience

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The importance of examining sex differences in animal models validated to induce an addiction-like phenotype

Cited by 9 publications

References 59 publications

Cyanidin prevents anxiety-like effects and dysregulation of cytokine systems during MDPV abstinence in rats

Cyanidin prevents anxiety-like effects and dysregulation of cytokine systems during MDPV abstinence in rats

Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats

mGlu5 inhibition in the basolateral amygdala prevents estrous cycle-dependent changes in cue-induced cocaine seeking

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