Adult consequences of repeated nicotine and Δ⁹-tetrahydrocannabinol (THC) vapor inhalation in adolescent rats

Abstract

The use of Electronic Drug Delivery Systems (EDDS, "e-cigarettes") to ingest nicotine and Δ9-tetrahydrocannabinol (THC) has surged in adolescent populations in the United States, as five times as many high-school seniors vape nicotine daily as use tobacco. At the same time 19.5% of seniors use cannabis at least monthly, with 12% using EDDS to deliver it. This study was conducted to examine the impact of repeated adolescent vapor inhalation of nicotine and THC in rats. Female Sprague-Dawley rats were exposed to 30-minute sessions of vapor inhalation, twice daily, from Post-Natal Day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle, Nicotine (60 mg/mL in the PG), THC (100 mg/mL in the PG) or the combination of Nicotine (60 mg/mL) and THC (100 mg/mL). Rats were assessed on wheel activity, heroin anti-nociception and nicotine and heroin vapor volitional exposure during adulthood. Nicotine exposed rats exhibited few differences as adults, but were less sensitive to anti-nociceptive effects of heroin (1 mg/kg, s.c.). THC- and THC+Nicotine-exposed rats were less spontaneously active, and obtained fewer nicotine vapor deliveries as adults. In contrast, THC exposed rats obtained volitional heroin vapor at rates indistinguishable from the non-THC-exposed groups. Repeated THC exposure also caused tolerance to temperature-disrupting effects of THC (5 mg/kg, i.p.). These studies further confirm that the effects of repeated vapor exposure to THC in adolescence last into early to middle adulthood, including decreased volitional consumption of nicotine. Effects of repeated nicotine in adolescence were comparatively minor.

Hyperactivity Induced By Vapor Inhalation of Nicotine in Male and Female Rats

“…Although several studies have examined sex differences in the locomotor effects of nicotine when administered by injection to laboratory rodents, relatively few studies have examined nicotine’s effects on locomotion when administered via inhalation. Several different assays of locomotor behavior, including open field assessment by videographic recording (Frie et al 2023; Gutierrez et al 2024b; Lallai et al 2021) or beam break (Alkhlaif and Shelton 2023; Roeder et al 2023), wheel activity (Gutierrez et al 2024a; Gutierrez et al 2024b) and radiotelemetry (Javadi-Paydar et al 2019a; Javadi-Paydar et al 2019b), have been used to determine effects of nicotine after vapor inhalation in rats. Despite methodological differences, cotinine levels of ∼20-50 ng/ml of plasma have been consistently reported across laboratory approaches within ∼30 minutes of vapor cessation in rats (Frie et al 2023; Gutierrez et al 2024b; Javadi-Paydar et al 2019b; Lallai et al 2021; Roeder et al 2023) and mice (Henderson and Cooper 2021; Lefever et al 2017).…”