Tolerance to hypothermic and antinoceptive effects of ∆9-tetrahydrocannabinol (THC) vapor inhalation in rats

Nguyen, Jacques D.; Grant, Yanabel; Kerr, Tony M.; Gutierrez, Arnold; Cole, Maury; Taffe, Michael A.

doi:10.1016/j.pbb.2018.07.007

Cited by 51 publications

(62 citation statements)

References 37 publications

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“…Due to reasonably frequent co-exposure of human cannabis users to nicotine (Cooper and Haney 2009;Eggers et al 2017;Ream et al 2008;Schauer et al 2017;Timberlake 2009), this study further determined the effects of co-exposure to THC and nicotine via vapor inhalation. Prior work with our inhalation model demonstrated consistent, dose-dependent hypothermic effects of THC inhalation and an inconsistent suppression of locomotor behavior in male and female Wistar, as well as male Sprague-Dawley, rats (Javadi-Paydar et al 2018a;Nguyen et al 2016b;Nguyen et al 2018). Parenteral injection of nicotine has previously been found to increase the hypothermia associated with injected THC (Pryor et al 1978;Valjent et al 2002), thus there was reason to expect similar effects in this model.…”

Section: Discussionsupporting

confidence: 53%

“…Injected nicotine has previously been shown to reduce body temperature and increase spontaneous locomotion in rats (Bryson et al 1981;Clemens et al 2009;Green et al 2003;Levin et al 2003), thus these measures were selected for initial validation. These have the additional advantages of supporting indirect crossdrug comparison with our prior reports on the effects of inhaled THC (Javadi-Paydar et al 2018a;Nguyen et al 2016b;Nguyen et al 2018) and psychomotor stimulants (Nguyen et al 2016a;Nguyen et al 2017). As in those prior studies, it was further important to contextualize some of the inhaled effects, including plasma nicotine and cotinine levels, with those produced by parenteral nicotine injection.…”

Section: Introductionmentioning

confidence: 86%

“…This relative paucity of information means that it is of pressing and significant interest to develop and validate experimental methods that can support a range of ENDS studies. We have recently developed a system capable of delivering behaviorally significant doses of THC (Javadi-Paydar et al 2018a;Nguyen et al 2016b;Nguyen et al 2018), as well as methamphetamine, mephedrone and 3,4-methylenedioxypyrovalerone (Nguyen et al 2016a;Nguyen et al 2017) to rats via the inhalation of ENDS vapor. This system has also been shown to support the self-administration of sufentanil with rats reaching dependence-inducing levels of drug intake via inhalation (Vendruscolo et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats

Javadi‐Paydar

Cole

Taffe

2018

Preprint

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Background: Electronic nicotine delivery systems (ENDS, e-cigarettes) are increasingly used for the self-administration of nicotine by various human populations, including previously nonsmoking adolescents. Studies in preclinical models are necessary to evaluate health impacts of ENDS including the development of nicotine addiction, effects of ENDS vehicles, flavorants and co-administered psychoactive substances such as ∆ 9 -tetrahydrocannabinol (THC). This study was conducted to validate a rat model useful for the study of nicotine effects delivered by inhalation of vapor created by ENDS.Methods: Male Sprague-Dawley rats (N=8) were prepared with radiotelemetry devices for the reporting of temperature and activity. Experiments subjected rats to inhalation of vapor generated by an electronic nicotine delivery system (ENDS) adapted for rodents. Inhalation conditions included vapor generated by the propylene glycol (PG) vehicle, Nicotine (1, 10, 30 mg/mL in the PG) and THC (12.5, 25 mg/mL). Results: Nicotine inhalation increased spontaneous locomotion and decreased body temperature of rats.Pretreatment with the nicotinic cholinergic receptor antagonist mecamylamine (2 mg/kg, i.p.) prevented stimulant effects of nicotine vapor inhalation and attenuated the hypothermic response. Combined inhalation of nicotine and THC resulted in apparently independent effects which were either additive (hypothermia) or opposed (activity). Conclusions:These studies provide evidence that ENDS delivery of nicotine via inhalation results in nicotine-typical effects on spontaneous locomotion and thermoregulation in male rats. Effects were blocked by a nicotinic antagonist, demonstrating mechanistic specificity. This system will therefore support additional studies of the contribution of atomizer/wick design, vehicle constituents and/or flavorants to the effects of nicotine administered by ENDS.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats

Javadi‐Paydar

Cole

Taffe

2018

Preprint

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“…Analysis of each treatment day revealed that AM11101 increased 1-hr food intake on five of 7 days, whereas THC's orexigenic effect was limited to 2 days. While previous studies have shown that THC's behavioural and physiological effects can dissipate in as few as four daily injections (Jarbe & DiPatrizio, 2005;Nguyen et al, 2018), we saw no evidence of tolerance to the orexigenic effects of THC or AM11101 in our study.…”

Section: Discussioncontrasting

confidence: 93%

The novel cannabinoid CB₁ receptor agonist AM11101 increases food intake in female rats

Ogden

Malamas

Makriyannis

et al. 2019

British J Pharmacology

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Background and Purpose Δ9‐tetrahydrocannabinol (THC) acts via cannabinoid CB1 receptors to increase feeding. Here, we assessed the orexigenic effect of AM11101, a novel CB1 receptor agonist designed to have a more favourable pharmacodynamic profile than THC. Experimental Approach The acute, orexigenic effects of AM11101 and THC were compared in female rats. Food intake and meal patterns were also examined following once daily treatment with AM11101 and THC for 7 days. Key Results AM11101 (0.01–0.1 mg·kg−1) increased food intake during the first hour following both acute and chronic treatments in pre‐fed and freely feeding animals. This orexigenic effect persisted for up to 4 hr, with no compensatory decrease in feeding during the subsequent 4–22 hr. THC (1 mg·kg−1) increased 1‐hr food intake in pre‐fed animals, but was less reliable than AM11101 in increasing 1‐hr food intake in freely feeding animals following both acute and chronic administration. The orexigenic effect of both compounds was due to an increase in meal size, not meal number. Conclusions and Implications Our study provides the first demonstration that AM11101 increases short‐term food intake via a selective increase in meal size. AM11101 promotes a more reliable orexigenic effect than THC in freely feeding animals, with no subsequent compensatory decrease in feeding. AM11101 may offer a greater efficacy than THC and its congeners in stimulating food intake in underweight clinical populations.

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“…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%

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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Tolerance to hypothermic and antinoceptive effects of ∆9-tetrahydrocannabinol (THC) vapor inhalation in rats

Abstract: Repeated daily THC inhalation induces tolerance in female and male rats, providing further validation of the vapor inhalation method for preclinical studies.

Cited by 51 publications

References 37 publications

Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats

Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats

The novel cannabinoid CB₁ receptor agonist AM11101 increases food intake in female rats

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

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Tolerance to hypothermic and antinoceptive effects of ∆9-tetrahydrocannabinol (THC) vapor inhalation in rats

Abstract: Repeated daily THC inhalation induces tolerance in female and male rats, providing further validation of the vapor inhalation method for preclinical studies.

Cited by 51 publications

References 37 publications

Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats

Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats

The novel cannabinoid CB1 receptor agonist AM11101 increases food intake in female rats

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

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The novel cannabinoid CB₁ receptor agonist AM11101 increases food intake in female rats