C. Cadoni et al., Behavioural sensitization after repeated exposure to Delta(9)-tetrahydrocannabinol and cross-sensitization with morphine, PSYCHOPHAR, 158(3), 2001, pp. 259-266
Rationale: Repeated exposure to several drugs of abuse has been reported to
induce behavioural sensitization. So far no evidence has been provided tha
t such a phenomenon also applies to cannabinoids. Objectives: In this study
we investigated if repeated exposure to Delta (9)-tetrahydrocannabinol (De
lta (9)-THC) induces behavioural sensitization. In addition we tested the p
ossibility of cross-sensitization between Delta (9)-THC and morphine. Metho
ds: Male Sprague-Dawley rats were administered for 3 days, twice daily, wit
h increasing doses of Delta (9)-tetrahydrocannabinol (2, 4 and 8 mg/kg i.p.
) or increasing doses of morphine (10, 20 and 40 mg/kg s.c.) or vehicle. Af
ter a washout of 14 days the animals were challenged with Delta (9)-THC (75
and 150 mug/kg i.v.), with a synthetic cannabinoid agonist WIN55212-2 (75
and 150 mug/kg i.v.) or with morphine (0.5 mg/kg i.v.), through a catheter
inserted into the left femoral vein 24 h before, and the behaviour recorded
. Results: Rats previously administered with Delta (9)-THC showed a greater
behavioural activation compared to controls in response to challenge with
Delta (9)-THC (150 mug/kg i.v.) and to challenge with morphine (0.5 mg/kg i
.v.). Similar to that observed after repeated opiates, this behavioural sen
sitization was characterized by stereotyped activity. Animals administered
with a schedule of morphine that induces behavioural sensitization to morph
ine also showed a behavioural sensitization to challenge with cannabinoids
(Delta (9)-THC and WIN55212-2, 75 and 150 mug/kg i.v.). The effect of the c
hallenge with Delta (9)-THC was prevented by the administration of the CB1
antagonist SR141716A (1 mg/kg i.p.), 40 min beforehand. Conclusions: The re
sults of the present study demonstrate that repeated exposure to Delta (9)-
THC induces behavioural sensitization not only to cannabinoids but also to
opiates. This cross-sensitization was symmetrical since rats behaviourally
sensitized to morphine were also sensitized to cannabinoids. These observat
ions further support the evidence of an interaction between the opioid and
the cannabinoid system and might provide a neurobiological basis for a rela
tionship between cannabis use and opiate abuse.