Premium
Delta‐9‐Tetrahydrocannabinol (THC) Self‐Administration in Male and Female Long Evans Rats
Author(s) -
Wakeford Alison GP,
Wetzell Bradley B,
Pomfrey Rebecca L,
Clasen Matthew,
Taylor William,
Riley Anthony L
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.703.1
Subject(s) - self administration , delta 9 tetrahydrocannabinol , tetrahydrocannabinol , cannabinoid , cannabidiol , medicine , pharmacology , δ9 tetrahydrocannabinol , drugs of abuse , drug , anesthesia , physiology , cannabis , psychiatry , receptor
Rationale Rodent preclinical assessments of THC self‐administration have failed to provide a robust and reliable animal model for the widespread use of marijuana in humans. Possibilities for this failure may be related to a) the lack of combining non‐psychoactive cannabinoids when examining THC self‐administration (given that marijuana derivatives abused by clinical populations contain cannabinoids other than THC) and b) the absence of assessments of sex differences in the acquisition of THC self‐administration (given that both clinical and preclinical data suggest that women may be more susceptible to drug use and abuse). Methods THC self administration was examined in male and female Long‐Evans rats under an FR1 schedule and across three doses (0.003, 0.01, 0.03 mg/kg/infusion). After each animal received five 2‐hour sessions with each dose (for a maximum of 15 days of intravenous self‐administration), they were then assessed for cocaine self‐administration (0.25 mg/kg/infusion; positive control) for 5 days or for THC self‐administration following pretreatment with cannabidiol at either a 1:1 or 1:10 CBD:THC ratio (all animals received both treatments, but were counterbalanced as to which treatment was received first). Results Discrimination between the active and inactive lever was found for almost all animals at the 0.03 mg/kg/infusion dose, but no sex differences appeared between active lever presses or number of infusions. All animals acquired cocaine self‐administration and received more infusions of cocaine than any THC dose examined with females self‐administering more cocaine than males. Overall, cannabidiol failed to impact THC self‐administration, although there were instances in which individual subjects were affected. Discussion The failure to find robust THC self‐administration under optimized conditions suggests THC acts as a weak reinforcer in rodent models of self‐administration. These results will be discussed in the context of previous self‐administration research in rodents and primates, along with future research projects that may elucidate mechanisms or other conditions under which rodents might robustly self‐administer THC in an effort to better understand and possibly treat marijuana abuse and dependence. Support or Funding Information Funding for this project was provided by American University's Office of Graduate Studies.