Cross-Generational THC Exposure Alters Heroin Reinforcement in Adult Male Offspring

Hempel, Briana; Crissman, Madeline E.; Imanalieva, Aikerim; Melkumyan, Mariam; Weiss, Tania D.; Winston, Chloe A.; Riley, Anthony L.

doi:10.1016/j.drugalcdep.2020.107985

Cited by 9 publications

(6 citation statements)

References 48 publications

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“…This is similar to Harlan Sprague–Dawley WIS rats that self-administered approximately 14–16 infusions of 0.015 mg/kg heroin during the first 2 h of their daily 6-h sessions (Lynch and Carroll 1999 ). Fourth, a 0.015 mg/kg dose of heroin also is positioned on the descending limb of the heroin dose–response curve studied under a fixed-ratio schedule in several rat strains (Martin et al 1998a , b ; Hiranita et al 2014 ; Hempel et al 2020 ). The only published report with heroin self-administration in SHR/NCrl demonstrated a dose of 0.030 mg/kg heroin was readily self-administered (Miller et al 2018 ) at levels lower than those reported in our pilot study for SHR/NCrl self-administering 0.015 mg/kg heroin.…”

Section: Methodsmentioning

confidence: 99%

Role of preexisting inhibitory control deficits vs. drug use history in mediating insensitivity to aversive consequences in a rat model of polysubstance use

et al. 2022

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Rationale The nature and predictors of insensitivity to aversive consequences of heroin + cocaine polysubstance use are not well characterized. Objectives Translational methods incorporating a tightly controlled animal model of drug self-administration and measures of inhibitory control and avoidance behavior might be helpful for clarifying this issue. Methods The key approach for distinguishing potential contributions of pre-existing inhibitory control deficits vs. drug use history in meditating insensitivity to aversive consequences was comparison of two rat strains: Wistar (WIS/Crl), an outbred strain, and the spontaneously hypertensive rat (SHR/NCrl), an inbred strain shown previously to exhibit heightened cocaine and heroin self-administration and poor inhibitory control relative to WIS/Crl. Results In separate tasks, SHR/NCrl displayed greater impulsive action and compulsive-like behavior than WIS/Crl prior to drug exposure. Under two different schedules of drug delivery, SHR/NCrl self-administered more cocaine than WIS/Crl, but self-administered a similar amount of heroin + cocaine as WIS/Crl. When half the session cycles were punished by random foot shock, SHR/NCrl initially were less sensitive to punishment than WIS/Crl when self-administering cocaine, but were similarly insensitive to punishment when self-administering heroin + cocaine. Based on correlation analyses, only trait impulsivity predicted avoidance capacity in rats self-administering cocaine and receiving yoked-saline. In contrast, only amount of drug use predicted avoidance capacity in rats self-administering heroin + cocaine. Additionally, baseline drug seeking and taking predicted punishment insensitivity in rats self-administering cocaine or heroin + cocaine. Conclusions Based on the findings revealed in this animal model, human laboratory research concerning the nature and predictors of insensitivity to aversive consequences in heroin and cocaine polysubstance vs. monosubstance users is warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s00213-022-06134-4.

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Section: Methodsmentioning

confidence: 99%

Role of preexisting inhibitory control deficits vs. drug use history in mediating insensitivity to aversive consequences in a rat model of polysubstance use

et al. 2022

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“…Multiple other studies addressing intergenerational effects of cannabinoids have now been reported but with key differences between experimental paradigms and in outcomes. For instance, a study similarly examining adolescent THC exposure in both parents, but in a different rats strain, reported reduced heroin reinforcement behaviour in male offspring 125 . The effects of THC exposure before conception in either the father or the mother have also been evaluated in independent studies.…”

Section: Intergenerational Impactmentioning

confidence: 99%

Cannabis and synaptic reprogramming of the developing brain

et al. 2021

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Recent years have been transformational in regard to the perception of the health risks and benefits of cannabis with increased acceptance of use. This has unintended neurodevelopmental implications given the increased use of cannabis and the potent levels of Δ 9 -tetrahydrocannabinol today being consumed by pregnant women, young mothers and teens. In this Review, we provide an overview of the neurobiological effects of cannabinoid exposure during prenatal/perinatal and adolescent periods, in which the endogenous cannabinoid system plays a fundamental role in neurodevelopmental processes. We highlight impaired synaptic plasticity as characteristic of developmental exposure and the important contribution of epigenetic reprogramming that maintains the long-term impact into adulthood and across generations. Such epigenetic influence by its very nature being highly responsive to the environment also provides the potential to diminish neural perturbations associated with developmental cannabis exposure.

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“…Sex differences (with females acquiring faster and taking more drug) have been reported 57,68,69 as has the absence of sex differences. 70,71 Withdrawal signs decreased significantly more in rapastinel-treated animals than in saline-treated animals from day 6 to day 9, although the distribution of specific withdrawal signs did not differ (data not shown). The physiologic basis of the signs tracked by Gellert and Holtzman (wet-dog shakes, diarrhea, mastication, salivation, ptosis and abnormal posture) are skewed toward peripheral autonomic effects likely mediated by increased activation of descending noradrenergic function by afferent input.…”

Section: Discussionmentioning

confidence: 88%

“…Sex differences (with females acquiring faster and taking more drug) have been reported 57, 68, 69 as has the absence of sex differences. 70, 71…”

Section: Discussionmentioning

confidence: 99%

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Rapastinel Accelerates Loss of Withdrawal Signs after Repeated Morphine and Blunts Relapse to Conditioned Place Preference

Armstrong

Ferrante

Lamichhane

et al. 2022

Preprint

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The purpose of the present study was to evaluate the efficacy of rapastinel, an allosteric modulator of NMDA receptor function, to accelerate the loss of opioid withdrawal symptoms and blunt or prevent relapse to morphine conditioned place preference (CPP) in rats. Two studies were conducted. In study 1, adult and adolescent male and female rats were treated with increasing doses of morphine (5 mg/kg, bid to 25 mg/kg bid) for 5 days. On day 6 animals were treated with naloxone (1 mg/kg) and withdrawal was assessed. They were then treated with saline or rapastinel (5 mg/kg) on days 6 and 8, and withdrawal assessed on day 9. Rapastinel treated animals exhibited significantly lower levels of withdrawal signs on day 9. No sex or age differences were observed. In Study 2, CPP for morphine was established in adult rats (males and females) by 4 daily pairings with saline and morphine (am/pm alternation). They were tested for CPP on day 5, and then treated with rapastinel (5 mg/kg) or saline daily on days 6-10 of extinction. On day 11 they received a final dose of rapastinel or saline followed by extinction. On day 12, animals received 1 mg/kg of morphine and were tested for relapse. Rapastinel did not affect extinction of CPP, but rapastinel-treated animals spent significantly less time in the previously morphine-paired side than saline-treated animals during the relapse trial. These findings of accelerated loss of withdrawal signs and blunted relapse to CPP suggest that rapastinel could provide an adjunctive therapy for opioid dependence during initiation of pharmacotherapy for opioid dependence.

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Cross-Generational THC Exposure Alters Heroin Reinforcement in Adult Male Offspring

Cited by 9 publications

References 48 publications

Role of preexisting inhibitory control deficits vs. drug use history in mediating insensitivity to aversive consequences in a rat model of polysubstance use

Role of preexisting inhibitory control deficits vs. drug use history in mediating insensitivity to aversive consequences in a rat model of polysubstance use

Cannabis and synaptic reprogramming of the developing brain

Rapastinel Accelerates Loss of Withdrawal Signs after Repeated Morphine and Blunts Relapse to Conditioned Place Preference

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