2,5-Dimethoxy-4-iodoamphetamine (DOI) inhibits Δ⁹- tetrahydrocannabinol-induced catalepsy-like immobilization in mice

The effect of the serotonin 5-HT_2A/2C-receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) on Δ⁹- tetrahydrocannabinol (THC)-induced catalepsy-like immobilization was studied in mice. DOI (0.3 and 1 mg/kg, i.p.) significantly inhibited the catalepsy-like immobilization induced by THC (10 mg/kg, i.p.). In contrast, the selective 5-HT_2C-receptor agonist 8,9-dichloro-2,3,4,4a-tetrahydro-1H- pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY 161503) had no effect on this catalepsy-like immobilization. Moreover, the 5-HT_2A-receptor antagonist ketanserin (0.3 mg/kg, i.p.) reversed the inhibition of THC-induced catalepsy-like immobilization caused by DOI (1 mg/kg), whereas the selective 5-HT_2C-receptor antagonist 6-chloro-2,3-dihydro-5-methyl-N-[6-(2- methyl-3-pyridinyl)oxyl]-3-pyridinyl]-1H-indole-1-carboxyamide (SB 242084) did not affect this inhibitory effect of DOI. On the other hand, ketanserin (0.3 and 1 mg/kg, i.p.) enhanced the catalepsy-like immobilization induced by THC (6 mg/kg, i.p.). Thus, on the basis of these results, it appears that 5-HT _2A-receptor mechanisms might be responsible for the inhibitory effect of DOI on THC-induced catalepsy-like immobilization.