Physical exercise modifies behavioral and molecular parameters related to opioid addiction regardless of training time

Rosa, Higor Zuquetto; Barcelos, Raquel Cristine Silva; Segat, Hecson Jesser; Roversi, Katiane; Dias, Verônica Tironi; Milanesi, Laura Hautrive; Bürger, Marilise Escobar

doi:10.1016/j.euroneuro.2019.12.111

Cited by 17 publications

(14 citation statements)

References 66 publications

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“…24 The results obtained from the current study indicated that the reinforcing effect of morphine was decreased after physical exercise in the drug-naïve offspring, which is in agreement with the results of a recent study. 25 However, the reinforcing effect of morphine increased in the MEO after mild physical exercise. In our previous work, the offspring of morphine-exposed rats was tolerant toward the reinforcing effect of morphine.…”

Section: Discussionmentioning

confidence: 98%

Exercise can restore behavioural and molecular changes of intergenerational morphine effects

et al. 2021

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In our previous studies, the offspring of morphine-exposed parents (MEO) showed pharmacological tolerance to the morphine's reinforcing effect. According to the role of exercise in treatment of morphine addiction, the current study was designed to utilize exercise to improve the effect of parental morphine exposure on the morphine's reinforcing effect. Male and female rats received morphine for 10 days and were drug-free for another 10 days. Each morphine-exposed animal was allowed to mate either with a drug-naïve or a morphine-exposed rat. The offspring were divided into two groups:(1) offspring that were subjected to treadmill exercise and (2) offspring that were not subjected to exercise. The reinforcing effect of morphine was evaluated using conditioned place preference (CPP) and two-bottle choice (TBC) tests. Levels of dopamine receptors (D1DR and D2DR), μ-opioid receptor (MOR), and ΔFosB were evaluated in the nucleus accumbens. The MEO obtained lower preference scores in CPP and consumed morphine more than the control group in TBC. After 3 weeks of exercise, the reinforcing effect of morphine in the MEO was similar to the control. D1DR, D2DR, and MOR were increased in MEO compared with the controls before exercise. Levels of D1DR and MOR were decreased after exercise in the MEO; however, D1DR was increased in control. D2DR level did not change after exercise in MEO, but it increased in control group. Moreover, the level of ΔFosB was decreased among MEO while it was increased after exercise. In conclusion, exercise might modulate the reinforcing effect of morphine via alteration in levels of D1DR, MOR, and ΔFosB.

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Section: Discussionmentioning

confidence: 98%

Exercise can restore behavioural and molecular changes of intergenerational morphine effects

et al. 2021

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“…Previous studies from our laboratory have shown CPP paradigm in experimental protocols related to AMPH addiction [14,29,30], besides other addictive substances such as cocaine [16] and morphine [31][32][33]. Thus, following drug extinction, events such as stress or drug re-exposure can reestablish the addiction, what may be experimentally observed by restoring the drug preference in the CPP paradigm [34].…”

Section: Discussionmentioning

confidence: 98%

Tactile Stimulation in Adult Rats Modulates Dopaminergic Molecular Parameters in the Nucleus Accumbens Preventing Amphetamine Relapse.

Rossato

Rosa

et al. 2022

Preprint

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Amphetamine (AMPH) is a psychostimulant drug frequently related to addiction, which is characterized by functional and molecular changes in the brain reward system, favoring relapse development and pharmacotherapies have shown low effectiveness. Considering the beneficial influences of tactile stimulation (TS) in different diseases that affect the central nervous system (CNS), here we evaluated if TS applied in adult rats could prevent or minimize the AMPH-relapse behavior also accessing molecular neuroadaptations in the Nucleus accumbens (NAc). Following AMPH conditioning in the conditioned place preference (CPP) paradigm, male rats were submitted to TS (15-min session, 3 times a day, for 8 days) during the drug abstinence period, which were re-exposed to the drug in the CPP paradigm for additional 3 days for relapse observation and molecular assessment. Our findings showed that besides AMPH relapse; TS prevented the dopamine transporter (DAT), dopamine 1 receptor (D1R), tyrosine hydroxylase (TH), mu opioid receptor (MOR) increase and AMPH-induced delta FosB (ΔFosB). Based on these outcomes, we propose TS as a useful tool to treat psychostimulant addiction, which subsequent to clinical studies; it could be included in detoxification programs together with pharmacotherapies and psychological treatments already conventionally established.

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“…This region, in particular, is associated with declarative memory and therefore plays a key role in the development of cue‐related memory, which may further promote the formation of maladaptive drug‐context associations 33 . Previous studies have demonstrated the crucial role of the hippocampus in the opioid‐associative learning process 34,35 . Arc is an effector of IEGs (immediate early genes) related to synaptic plasticity, robustly induced by exposure to opiates, 36 and particularly involved in relapse.…”

Section: Discussionmentioning

confidence: 99%

“…33 Previous studies have demonstrated the crucial role of the hippocampus in the opioid-associative learning process. 34,35 Arc is an effector of IEGs (immediate early genes) related to synaptic plasticity, robustly induced by exposure to opiates, 36 and particularly involved in relapse. Dlg1 or Dlg4 is responsible for the glutamatergic synapse maturation 37 and its expression is potentially related to the induction of drug seeking behavior.…”

Section: Oxytocin Decreased Mrna Levels and Synaptic Density In Oxyco...mentioning

confidence: 99%

Oxytocin prevents cue‐induced reinstatement of oxycodone seeking: Involvement of DNA methylation in the hippocampus

Fan

Shi

et al. 2021

Addiction Biology

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Oxycodone is one of the most commonly used analgesics in the clinic. However, long‐term use can contribute to drug dependence. Accumulating evidence of changes in DNA methylation after opioid relapse has provided insight into mechanisms underlying drug‐associated memory. The neuropeptide oxytocin is reported to be a potential treatment for addiction. The present study sought to identify changes in global and synaptic gene methylation after cue‐induced reinstatement of oxycodone conditioned place preference (CPP) and the effect of oxytocin. We analyzed hippocampal mRNA of synaptic genes and also synaptic density in response to oxycodone CPP. We determined the mRNA levels of DNA methyltransferases (Dnmts) and ten‐eleven translocations (Tets), observed global 5‐methylcytosine (5‐mC) and 5‐hydroxymethylcytosine (5‐hmC) levels, and measured DNA methylation status of four synaptic genes implicated in learning and memory (Arc, Dlg1, Dlg4, and Syn1). Both synaptic density and the transcription of 15 hippocampal synaptic genes significantly increased following cue‐induced reinstatement of oxycodone CPP. Oxycodone relapse was also related to markedly decreased 5‐mC levels and decreased transcription of Dnmt1, Dnmt3a, and Dnmt3b; in contrast, 5‐hmC levels and the transcription of Tet1 and Tet3 were increased. Oxycodone exposure induced DNA hypomethylation at the exons of the Arc, Dlg1, Dlg4, and Syn1 genes. Intracerebroventricular (ICV) administration of oxytocin (2.5 μg/μl) specifically blocked oxycodone relapse, possibly by inhibition of Arc, Dlg1, Dlg4, and Syn1 hypomethylation in oxycodone‐treated rats. Together, these data indicate the occurrence of epigenetic changes in the hippocampus following oxycodone relapse and the potential role of oxytocin in oxycodone addiction.

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Physical exercise modifies behavioral and molecular parameters related to opioid addiction regardless of training time

Cited by 17 publications

References 66 publications

Exercise can restore behavioural and molecular changes of intergenerational morphine effects

Exercise can restore behavioural and molecular changes of intergenerational morphine effects

Tactile Stimulation in Adult Rats Modulates Dopaminergic Molecular Parameters in the Nucleus Accumbens Preventing Amphetamine Relapse.

Oxytocin prevents cue‐induced reinstatement of oxycodone seeking: Involvement of DNA methylation in the hippocampus

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