Variability in the effects of 4-bromo-2,5-dimethoxyamphetamine (DOB) on operant behavior of squirrel monkeys.

Effects of the hallucinogenic drug (+/-)-4-bromo-2,5-dimethoxyamphetamine HCl (DOB, 0.003-0.3 mg/kg) were studied in squirrel monkeys. Only decreases in responding were seen in monkeys studied under 5-min fixed-interval schedules of food presentation. These decreases were blocked by pretreatment with the 5-HT2 antagonist ketanserin (0.1-1.0 mg/kg) and by the non-selective 5-HT antagonists methysergide (0.3 mg/kg) or mianserin (0.1-1.0 mg/kg). Similar decreases in responding and antagonism by 5-HT antagonists were seen at slightly higher doses of DOM HCl (methyl rather than bromo at the 4 position). In contrast to effects under the food schedule, DOB initially produced marked increases in responding of three monkeys studied under schedules of shock avoidance. However, a complex pattern of changes in the effects of DOB emerged when the same doses were given on subsequent occasions. In one monkey, there were graded increases in responding to a peak of just over 200% of control at 0.17 mg/kg when DOB was given in a roughly ascending dose series. However, no increases in responding were observed at any dose when DOB was given on many subsequent occasions (some very widely spaced). A second monkey showed similar increases initially, but responding was suppressed by a formerly rate-increasing dose of DOB (0.1 mg/kg) on two subsequent test days. Later, this dose again produced increases in responding of about the same magnitude as seen initially, but these increases eventually diminished and were no longer observed. In the third monkey, increases in responding after the initial ascending dose series diminished in an irregular manner over the course of successive redeterminations.