Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents

Guglielmo, Giordano de; Kallupi, Marsida; Scuppa, Giulia; Demopulos, Gregory; Gaitanaris, George A.; Ciccocioppo, Roberto

doi:10.1007/s00213-016-4452-1

Cited by 42 publications

(29 citation statements)

References 37 publications

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“…PPARγ receptor activation by PIO was found to significantly reduce alcohol/ethanol consumption, and relapse to alcohol seeking (Ferguson et al, 2014; Stopponi et al, 2011; Stopponi et al, 2013). Other rodent work has found similarly promising results with opioids, cocaine and methamphetamine (Ciccocioppo et al, 2012; de Guglielmo et al, 2017; Maeda et al, 2007; Miller, 2016). Concerning preclinical findings with nicotine, PPAR alpha agonists have been found to block nicotine reward and induced reinstatement of drug seeking (Mascia et al, 2011; Panlilio et al, 2012).…”

Section: Introductionmentioning

confidence: 74%

Pioglitazone, a PPARγ agonist, reduces nicotine craving in humans, with marginal effects on abuse potential

Jones

Comer

Metz

et al. 2017

Pharmacology Biochemistry and Behavior

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Possibly through their actions upon glia, peroxisome proliferator-activated receptor agonists (PPAR) have been shown to alter the abuse potential of addictive drugs in several preclinical models. The current study extends this research into the human laboratory as the first clinical study into the effects of the PPAR gamma agonist, pioglitazone, on the abuse potential of nicotine. Heavy smokers were recruited for this 3-week study. Upon admission, participants were randomized to either active (45 mg, n = 14) or placebo (0 mg, n = 13) PIO maintenance conditions for the duration of the study. After 5–7 days of stabilization on a 7 mg nicotine patch, participants began laboratory testing. On the 1st–4th test days, participants could self-administer cigarettes or receive money by making verbal choices for either option. On the 5th day, participants were administered 10 puffs of their usual brand of cigarette in the morning and later chose between smoking and money by making finger presses on a computer mouse in a progressive ratio self-administration task. Later on the 5th day participants also underwent a smoking cue exposure session. The 8th–11th test days were identical to the 1st–4th test days with the exception that during one of the test weeks de-nicotinized cigarettes were available, and during the other nicotinized cigarettes were available. Nicotinized cigarettes were always administered on the 5th and 12th days. On some measures PIO increased indicators of abuse potential, though this effect was typically not statistically significant. However, PIO did significantly reduce measures of craving.

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Section: Introductionmentioning

confidence: 74%

Pioglitazone, a PPARγ agonist, reduces nicotine craving in humans, with marginal effects on abuse potential

Jones

Comer

Metz

et al. 2017

Pharmacology Biochemistry and Behavior

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“…In this regard, Willcocks and McNally [149] showed that reversible inactivation of dmPFC decreases context-induced reinstatement of alcohol seeking but accelerates acquisition of alcohol self-administration after extinction. Other evidence that suggests that reinstatement and reacquisition of opioid-taking behavior involve dissociable mechanisms is that yohimbine reliably reinstates opioid seeking after extinction [150,151], but has no effect on reacquisition of heroin self-administration [110].…”

Section: Discussionmentioning

confidence: 99%

Relapse to opioid seeking in rat models: behavior, pharmacology and circuits

Reiner

Fredriksson

Lofaro

et al. 2018

Neuropsychopharmacol

117

101

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Lifetime relapse rates remain a major obstacle in addressing the current opioid crisis. Relapse to opioid use can be modeled in rodent studies where drug self-administration is followed by a period of abstinence and a subsequent test for drug seeking. Abstinence can be achieved through extinction training, forced abstinence, or voluntary abstinence. Voluntary abstinence can be accomplished by introducing adverse consequences of continued drug self-administration (e.g., punishment or electric barrier) or by introducing an alternative nondrug reward in a discrete choice procedure (drug versus palatable food or social interaction). In this review, we first discuss pharmacological and circuit mechanisms of opioid seeking, as assessed in the classical extinctionreinstatement model, where reinstatement is induced by reexposure to the self-administered drug (drug priming), discrete cues, discriminative cues, drug-associated contexts, different forms of stress, or withdrawal states. Next, we discuss pharmacological and circuit mechanisms of relapse after forced or voluntary abstinence, including the phenomenon of "incubation of heroin craving" (the time-dependent increases in heroin seeking during abstinence). We conclude by discussing future directions of preclinical relapse-related studies using opioid drugs.Neuropsychopharmacology (2019) 44:465-477; https://doi.[143] 1Note: Several reinstatement-related papers published results with more than one reinstating stimulus (e.g., drug priming and stress, drug priming and drug cue) and appear in more than one category. Historical citations refer to the initial papers published with a given model.Relapse to opioid seeking in rat models: behavior, pharmacology and. . . DJ Reiner et al.Neuropsychopharmacology (2019) 44:465 -477 1234567890();,:Relapse to opioid seeking in rat models: behavior, pharmacology and. . . DJ Reiner et al.

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“…PPARγ is expressed primarily in microglia and PPARγ agonists inhibit the expression of proinflammatory cytokines (Kielian and Drew, 2003). Recent studies show that stimulation of PPARγ reduces heroin self-administration and reinstatement of heroin seeking (de Guglielmo et al, 2016, 2015). …”

Section: Drugs Of Abuse and Glial Cell Activitymentioning

confidence: 99%

“…Interest in PPARγ agonists has grown in many neuroinflammatory disorders due to the expression of PPARγ primarily in microglia and the ability of PPARγ agonists to inhibit the expression of cytokines by monocytes/macrophages and microglia (Kielian and Drew, 2003). In response to the promising preclinical research (de Guglielmo et al, 2016, 2015), researchers sought to test the ability of PIO to alter the abuse potential of opioids in human subjects. One of these trials maintained non-dependent prescription opioid abusers (n=17 completers) on an ascending daily dose of PIO (0 mg, 15 mg, 45 mg) for 2–3 weeks per dose.…”

Section: Drugs Of Abuse and Glial Cell Activitymentioning

confidence: 99%

Glial and neuroinflammatory targets for treating substance use disorders

Bachtell

Jones

Heinzerling

et al. 2017

Drug and Alcohol Dependence

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Background The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders. Consequently, drug-induced changes in glia-driven processes in the brain represent potential targets for pharmacotherapeutics treating substance use disorders. Methods Four speakers presented preclinical and clinical research illustrating the effects that glial modulators have on abuse-related behavioral effects of psychostimulants and opioids. This review highlights some of these findings and expands its focus to include other research focused on drug-induced glia abnormalities and glia-focused treatment approaches in substance use disorders. Results Preclinical findings show that drugs of abuse induce neuroinflammatory signals and disrupt glutamate homeostasis through their interaction with microglia and astrocytes. Preclinical and clinical studies testing the effects of glial modulators show general effectiveness in reducing behaviors associated with substance use disorders. Conclusions The contribution of drug-induced glial activity continues to emerge as an intriguing target for substance use disorder treatments. Clinical investigations of glial modulators have yielded promising results on substance use measures and indicate that they are generally safe and well-tolerated. However, results have not been entirely positive and more questions remain for continued exploration in the development and testing of glial-directed treatments for substance use disorders.

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Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents

Abstract: These findings provide new insights on the role of PPARγ on opioid dependence and suggest that pioglitazone may be useful for the treatment of opioid withdrawal in opioid-addicted individuals.

Cited by 42 publications

References 37 publications

Pioglitazone, a PPARγ agonist, reduces nicotine craving in humans, with marginal effects on abuse potential

Pioglitazone, a PPARγ agonist, reduces nicotine craving in humans, with marginal effects on abuse potential

Relapse to opioid seeking in rat models: behavior, pharmacology and circuits

Glial and neuroinflammatory targets for treating substance use disorders

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