Effects of DOM and DMT in a proposed animal model of hallucinogenic activity.

A previously proposed animal model of lysergic acid diethylamide's (LSD) effects in humans was tested for its applicability to other hallucinogens, 2,5-dimethoxy-4-methyl amphetamine (DOM) and N,N-dimethyltryptamine (DMT). Both "free" and "forced" exploration tests in a behavioral pattern monitor were used to determine the effects of these hallucinogens on the normal tendencies of rats to avoid novel and central areas, respectively. The effects of DOM (0.3-1.0 mg/kg) were quite similar to those previously reported for LSD. Specifically, DOM reduced crossovers, holepokes, and rearings when rats were tested in a novel environment. In a familiar environment, only rearing activity was reduced with minimal effect on ambulation. Like LSD, entries into the central area were reduced in both situations. DOM also produced a dose-dependent reduction of entries into the novel chamber in a free exploration test. Pretreatment with the serotonin (5-HT) antagonist cyproheptadine (1.0 mg/kg), which does not block the psychological effects of hallucinogens in humans, selectively blocked DOM's reduction of rearings without altering DOM's reduction of center entries, crossovers, or holepokes. Like LSD and DOM, DMT (0.5, 1.0, and 2.0 mg/kg) produced a selective reduction of entries into the center region when rats were forced to explore a novel holeboard chamber. All three doses also selectively reduced holepoke responses without affecting crossovers or rearings. In conclusion, enhanced avoidance of novel and central areas appears to be a valid indicator of hallucinogenic activity since LSD, DMT, and DOM all share this property. Conversely, the reduction of rearings produced by LSD and DOM is not a suitable model behavior since the effect is not produced by DMT and cyproheptadine is capable of selectively blocking this effect.