Skip to content

Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats

Jacques D. Nguyen, Kevin M Creehan, Tony M Kerr, Michael A. Taffe

bioRxiv (Cold Spring Harbor Laboratory) September 25, 2018 preprint DOI: 10.1101/426064 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled animal experiment
Population Male and female adolescent rats (postnatal days 35-45), followed into adulthood
Intervention THC vapor inhalation
Duration Twice daily for 30 minutes from postnatal day 35-39 and 42-45; follow-up from postnatal day 86-94 and in adulthood
Measures radio-telemetry thermoregulatory responses, chow intake, plasma THC levels, intravenous self-administration of oxycodone, fentanyl self-administration
Topics Cannabis
Citations 9
Key findings Repeated adolescent THC vapor inhalation produced lasting effects in rats: females, but not males, developed tolerance to THC-induced hypothermia during adolescence despite similar plasma THC levels, and both sexes showed adult tolerance with greater potency in females. THC-exposed males ate more chow than controls without weight differences, and THC increased adult fentanyl self-administration in females but did not alter oxycodone self-administration in either sex.

Abstract

Abstract Adolescents are regularly exposed to Δ 9 -tetrahydrocannabinol (THC) via smoking, and, more recently, vaping, cannabis / extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behavior and lasting tolerance in response to THC. Male and female rats inhaled THC vapor, or that from the propylene glycol (PG) vehicle, twice daily for 30 minutes from postnatal day (PND) 35-39 and PND 42-45 using an e-cigarette system. Thermoregulatory responses to vapor inhalation were assessed by radio-telemetry during adolescence and from PND 86-94; chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after four days of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults. Female, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC with THC greater potency exhibited in females. Repeated-THC male rats consumed more food than their PG treated control group, in the absence of a significant bodyweight difference. Adolescent THC did not alter oxycodone self-administration in either sex, but increased fentanyl self-administration in females. Repeated THC vapor inhalation in adolescent rats results in lasting consequences observable in adulthood. Abbreviations PG, propylene glycol; THC, Δ 9 tetrahydrocannabinol;

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

Citations in the library

Explore topics