Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats

Javadi‐Paydar, Mehrak; Nguyen, Jacques D.; Kerr, Tony M.; Grant, Yanabel; Vandewater, Sophia A.; Cole, Maury; Taffe, Michael A.

doi:10.1007/s00213-018-4946-0

Cited by 84 publications

(109 citation statements)

References 52 publications

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“…ENDS are relatively new for the field and are being used by multiple labs to vaporize and deliver various drugs to rodents via inhalation. Published work shows that ENDS can be used to vaporize and deliver nicotine (Javadi-Paydar et al 2019), THC (Nguyen et al 2016aJavadi-Paydar et al 2018, opiates (Vendruscolo et al 2018), stimulants (Nguyen et al 2017), or combinations of these drugs (Javadi-Paydar et al 2019) to rats on experimenter-determined schedules, and that these exposures produce expected blooddrug levels, relative to prior work using other systemic routes of drug administration. Furthermore, for many of these drugs, labs are working to establish reliable e-cigarette vapor self-administration using operant tasks that can be learned, extinguished, and altered according to drug concentrations in the vape solution.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to other studies (Nguyen et al 2016a(Nguyen et al , 2016b(Nguyen et al , 2017Javadi-Paydar et al 2018Vendruscolo et al 2018) that delivered drugs through ENDS to rodents, we did not measure the drug concentration in the air of the chambers and in the fur of rats, or conduct an epidermal tissue biopsy. While nicotine vapor exposure in a chamber does not exclude uptake through skin/fur absorption or grooming, such effects seems to be negligible compared to inhalation effects observed in rodents following nicotine wholebody vapor exposure through ENDS (see Milano et al 2019 for a review).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we began using ENDS to deliver vaporized drugs to rodents in standard housing chambers. This method has been used to administer vaporized Δ9-tetrahydrocannabinol (THC; Nguyen et al 2016aNguyen et al , 2018Javadi-Paydar et al 2018, opiates (Vendruscolo et al 2018), stimulants (Nguyen et al 2016b(Nguyen et al , 2017, nicotine (Javadi-Paydar et al 2019), or combinations of these drugs (Javadi-Paydar et al 2019). ENDS nicotine inhalation produces behavioral and physiological effects in rats, such as increases in spontaneous locomotor activity and decreases in body temperature (Javadi-Paydar et al 2019).…”

Section: Introductionmentioning

confidence: 99%

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Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats

Montanari

Kelley

Kerr

et al. 2019

Preprint

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Rationale: Non-contingent chronic nicotine exposure procedures have evolved rapidly in recent years, culminating in Electronic Nicotine Delivery Systems (ENDS or e-cigarettes) to deliver vaporized drugs to rodents in standard housing chambers. Objectives:The aim of the current work was to use ENDS to test concentration-dependent effects of nicotine e-cigarette vapor inhalation on blood-nicotine concentrations, blood-cotinine concentrations, and somatic withdrawal signs over time in rats.Methods: Male Wistar rats were exposed to vapor containing various concentrations of nicotine (20, 40, 80 mg/mL) for 11 days through ENDS, and blood concentrations of nicotine and cotinine, the major proximate metabolite of nicotine, as well as spontaneous and precipitated somatic withdrawal signs were measured over time (across days of exposure and over hours after termination of vapor exposure).Results: Exposing male Wistar rats to non-contingent nicotine vapor inhalation through ENDS produces somatic withdrawal symptoms and measurable blood-nicotine and blood-cotinine levels that change according to 1) concentration of nicotine in vape solution, 2) number of days of nicotine vapor exposure, 3) time since termination of nicotine vapor exposure, and 4) relative to the withdrawal signs, whether withdrawal was spontaneous or precipitated (by mecamylamine). Conclusions:The data presented here provide parameters that can be used as a reasonable starting point for future work that employs ENDS to deliver non-contingent nicotine vapor in rats, although many parameters can and should be altered to match the specific goals of future work.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats

Montanari

Kelley

Kerr

et al. 2019

Preprint

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“…Cannabis extracts rich in THC (CANTHC; 28.4% THC/1.1% CBD) or CBD (CANCBD; 1.96% THC/59.3% CBD) were heated to 60°C under constant stirring and dissolved in 80% propylene glycol/20% vegetable glycerol vehicle (VEH) at a concentration of 400 mg/ml based on previous studies [25,26]. Based on the certificate of analysis provided by NIDA, the final concentrations of THC and CBD in CANTHC were ~116.8 mg/ml and ~4.4 mg/ml, respectively.…”

Section: Drugsmentioning

confidence: 99%

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

Freels

Baxter-Potter

Lugo

et al. 2019

Preprint

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Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug employed and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized ∆9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) complete cannabis extracts. Male Sprague Dawley rats were trained to nosepoke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily one-hour sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared to CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors. Cannabis vapor self-administration

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“…Moreover, synthetic CB1 receptor agonists are known to recruit different intracellular signaling cascades (Laprairie et al, 2014(Laprairie et al, , 2016 and differences in pharmacokinetics due to the route of administration can dramatically influence the amount of fetal exposure (McLaughlin, 2018). More recently, a cannabis vapor delivery system has been introduced to more closely mimic the intrapulmonary route of administration that is most common among human cannabis users (Freels et al, 2020;Javadi-Paydar et al, 2018;Nguyen et al, 2016). This approach takes advantage of commercial 'e-cigarette' technology to deliver vaporized whole-plant cannabis extracts to rodents that results in pharmacologically and behaviorally relevant cannabinoid concentrations in plasma and brain tissue (Freels et al, 2020;Nguyen et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Maternal cannabis vapor exposure causes long-term alterations in emotional reactivity, social behavior, and behavioral flexibility in offspring

Weimar

Wright

Warrick

et al. 2020

Preprint

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wordsMaternal cannabis vapor exposure AbstractThe use of cannabis during pregnancy is a growing public health concern. As more states implement legislation permitting recreational cannabis use, there is an urgent need to better understand its impact on fetal neurodevelopment and its long-term effects in exposed offspring.Studies examining effects of prenatal cannabis exposure typically employ injections of synthetic cannabinoids or isolated cannabis constituents that may not accurately model cannabis use in human populations. To address this limitation, we have developed a novel e-cigarette technologybased system to deliver vaporized cannabis extracts to pregnant Long Evans rats. We used this model to determine effects of prenatal cannabis exposure on emotional, social, and cognitive endpoints of male and female offspring during early development and into adulthood. Dams were exposed to cannabis vapor (CANTHC: 400 mg/ml), vehicle vapor (VEH), or no vapor (AIR) twice daily during mating and gestation. Offspring exposed to CANTHC and VEH showed reduced weight gain relative to AIR offspring prior to weaning. CANTHC offspring made more isolation-induced ultrasonic vocalizations (USVs) on postnatal day 6 (P6) relative to VEH-exposed offspring, which is indicative of increased emotional reactivity. Male CANTHC offspring engaged in fewer social investigation behaviors than VEH-exposed male offspring during a social play test on P26. In adulthood, CANTHC-exposed offspring spent less time exploring the open arms of the elevated plus maze and exhibited dose-dependent deficits in behavioral flexibility in an attentional setshifting task relative to AIR controls. These data collectively indicate that prenatal cannabis exposure causes enduring effects on the behavioral profile of offspring.Maternal cannabis vapor exposure

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Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats

Abstract: In summary, the inhalation of THC or CBD, alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette-based method of THC delivery in female rats.

Cited by 84 publications

References 52 publications

Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats

Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

Maternal cannabis vapor exposure causes long-term alterations in emotional reactivity, social behavior, and behavioral flexibility in offspring

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