Comparative effects of pulmonary and parenteral Δ⁹-tetrahydrocannabinol exposure on extinction of opiate-induced conditioned aversion in rats.
BACKGROUND
Evidence suggesting that the endogenous cannabinoid (eCB) system can be manipulated to facilitate or impair extinction of learned behaviours has important consequences for opiate withdrawal and abstinence. We demonstrated that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases eCB levels, facilitates extinction of a naloxone-precipitated morphine withdrawal-induced conditioned place aversion (CPA).


OBJECTIVE
The potential of the exogenous CB1 ligand, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), to facilitate extinction of this CPA was tested. Effects of both pulmonary and parenteral Δ(9)-THC exposure were evaluated using comparable doses previously determined.


METHODS
Rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered Δ(9)-THC-pulmonary (1, 5, 10 mg vapour inhalation) or parenteral (0.5, 1.0, 1.5 mg/kg intraperitoneal injection)-prior to each of 20 to 28 extinction/testing trials.


RESULTS
Vapourized Δ(9)-THC facilitated extinction of the CPA in a dose- and time-dependent manner: 5 and 10 mg facilitated extinction compared to vehicle and 1 mg Δ(9)-THC. Injected Δ(9)-THC significantly impaired extinction only for the 1.0-mg/kg dose: it prolonged the CPA fourfold longer than the vehicle and 0.5- and 1.5-mg/kg doses.


CONCLUSIONS
These data suggest that both dose and route of Δ(9)-THC administration have important consequences for its pharmacokinetic and behavioural effects; specifically, pulmonary exposure at higher doses facilitates, whereas pulmonary and parenteral exposure at lower doses impairs, rates of extinction learning for CPA. Pulmonary-administered Δ(9)-THC may prove beneficial for potentiation of extinction learning for aversive memories, such as those supporting drug-craving/seeking in opiate withdrawal syndrome, and other causes of conditioned aversions, such as illness and stress.
Department of Psychology, Wilfrid Laurier University, Waterloo, ON, N2L3C5, Canada, laurie.manwell@camh.ca.
Laurie A
LA
Manwell
Paul E
PE
Mallet
D000280:Administration, Inhalation; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D013759:Dronabinol / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D063386:Cannabinoid Receptor Agonists; D009270:Naloxone; D009020:Morphine; D013759:Dronabinol