The time-dependent stimulus effects of R(-)-2,5-dimethoxy-4-methamphetamine (DOM): implications for drug-induced stimulus control as a method for the study of hallucinogenic agents

The pharmacodynamic characteristics of the stimulus effects of the hallucinogens d-LSD and (-)DOM were investigated in the rat. The stimulus control induced by (-)DOM (0.56 mg/kg) was significantly less stable at the 15-min pretreatment time than at the 75-min pretreatment time. In addition, (-)DOM (0.8 mg/kg) produced a time-dependent substitution for the LSD stimulus in LSD trained subjects (0.1 mg/kg, 15-min pretreatment time). As pretreatment times were increased, the substitution of (-)DOM (0.8 mg/kg) for the LSD stimulus increased, culminating in a maximal level of 99.5% LSD-appropriate responding at the 75-min pre-treatment time. A dose-response relationship for the substitution of (-)DOM (75-min pretreatment time) for the LSD stimulus, indicated that 0.2 mg/kg (-)DOM was the minimum dose which elicited greater than 90% LSD-appropriate responding. LSD (0.32 mg/kg, 15-min pretreatment time) fully substituted for (-)DOM in the (-)DOM trained subjects (0.56 mg/kg, 75-min pretreatment time). These findings suggest that the pharmacodynamic parameters of d-LSD and (-)DOM-induced stimulus control differ. The time of onset for the stimulus effects of (-)DOM is markedly longer than that of LSD in the rat.