Dissociation of heroin-induced emotional dysfunction from psychomotor activation and physical dependence among inbred mouse strains

Ayrancı, Gülebru; Befort, Katia; Lalanne, Laurence; Kieffer, Brigitte L.; Lutz, Pierre-Eric

doi:10.1007/s00213-014-3826-5

Cited by 7 publications

(6 citation statements)

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“…Morphine abstinent mice displayed impaired direct social interaction, deficient nest building and compromised social preference, indicative of altered social behavior. These results match previous reports that protracted abstinence from chronic escalating opiate treatment produces social behavior deficits in rodents (Ayranci et al, 2014; Goeldner et al, 2011; Lutz et al, 2014; Zanos et al, 2014), as well as clinical reports describing social cognition/judgment deficits in patients under opioid maintenance (Johnson et al, 2014; McDonald et al, 2013). Alcohol, nicotine and THC abstinent mice also exhibited reduced social interaction.…”

Section: Discussionsupporting

confidence: 91%

“…These behavioral modifications differed across mouse strains (Ayranci et al, 2015) and were enhanced or reduced by genetic inactivation of delta and kappa opioid receptors, respectively (Lutz et al, 2014). We also tested gene expression for a large set of genes in the extended amygdala (EA), a key site contributing to hedonic and stress-related dysfunction in drug abuse.…”

Section: Introductionmentioning

confidence: 99%

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Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol

2016

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Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, i9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these 4 drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies, and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol

2016

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“…Although the previous finding reported that acute mitragynine may have anxiolytic effects ( Farah et al, 2011 ; Hazim et al, 2014 ; Yusoff et al, 2016 ), our present data showed a lack of social interaction which suggests that mitragynine, regardless of the doses and LKD may induce anxiogenic effects in adolescent rats, affecting social behaviour in a novel environment. A growing literature investigating the effects of drug abuse on social behaviour in rodents demonstrates that drugs influence social behaviour ( Ayranci et al, 2014 ; Becker et al, 2017 ; Listos et al, 2022 ), especially in adolescence ( Kuhn, 2015 ). For instance, repeated alcohol exposure increases anxiety-like behaviour under social circumstances in adolescents but not in adult animals, as indicated by a decrease in social preference ( Varlinskaya and Spear, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Adolescent kratom exposure affects cognitive behaviours and brain metabolite profiles in Sprague-Dawley rats

et al. 2022

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Adolescence is a critical developmental period during which exposure to psychoactive substances like kratom (Mitragyna speciosa) can cause long-lasting deleterious effects. Here, we evaluated the effects of mitragynine, the main alkaloid of kratom, and lyophilised kratom decoction (LKD) on cognitive behaviours and brain metabolite profiles in adolescent rats. Male Sprague-Dawley rats (Postnatal day, PND31) were given vehicle, morphine (5 mg/kg), mitragynine (3, 10, or 30 mg/kg), or LKD (equivalent dose of 30 mg/kg mitragynine) for 15 consecutive days. Later, a battery of behavioural testing was conducted, brain was extracted and metabolomic analysis was performed using LCMS-QTOF. The results showed that mitragynine did not affect the recognition memory in the novel object recognition task. In the social interaction task, morphine, mitragynine, and LKD caused a marked deficit in social behaviour, while in Morris water maze task, mitragynine and LKD only affected reference memory. Metabolomic analysis revealed distinct metabolite profiles of animals with different treatments. Several pathways that may be involved in the effects of kratom exposure include arachidonic acid, pantothenate and CoA, and tryptophan pathways, with several potential biomarkers identified. These findings suggest that adolescent kratom exposure can cause cognitive behavioural deficits that may be associated with changes in the brain metabolite profiles.

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“…; Ayranci et al . ) and occurred before the emergence of despair‐like behavior at 7 weeks of abstinence (Lutz et al . ), suggesting that deficient sociability precedes mood disruption during ongoing heroin abstinence.…”

Section: Discussionmentioning

confidence: 99%

Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence

et al. 2016

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Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, ‘abstinent’ mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals.

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Dissociation of heroin-induced emotional dysfunction from psychomotor activation and physical dependence among inbred mouse strains

Abstract: Our results indicate that depressive-like behaviors emerge during heroin abstinence, whatever the severity of immediate behavioral responses to the drug. In addition, inbred mouse strains will allow studying several aspects of mood-related deficits associated with addiction.

Cited by 7 publications

References 74 publications

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol

Adolescent kratom exposure affects cognitive behaviours and brain metabolite profiles in Sprague-Dawley rats

Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence

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