Figure 1.
Tolerance develops to the anti-migraine effects of morphine, but not THC. Animals were pretreated with THC (1.0 mg/kg), morphine (3.2 mg/kg) or vehicle for 2.5 days. Microinjection of AITC onto the dura mater produced migraine-like pain indicated by depression of wheel running that lasted for at least 3 h in all experiments. A) Administration of 0.32 mg/kg of THC immediately after AITC administration prevented AITC-induced depression of wheel running in vehicle- (upper panel) and THC-treated animals (lower panel). Administration of a lower dose of THC (0.1 mg/kg) or vehicle did not prevent AITC-induced depression of wheel running (n = 5–7/group). B) In saline-pretreated animals, administration of 1.0 mg/kg of morphine immediately after AITC administration prevented AITC-induced depression of wheel running (upper panel). This antinociceptive effect was absent in morphine-pretreated animals as would be expected with the development of tolerance (lower panel) (n = 6–8/group).