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Variability in the effects of 4-bromo-2,5-dimethoxyamphetamine (DOB) on operant behavior of squirrel monkeys
1Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545.
Abstract:
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.
Insights
The hallucinogenic drug DOB initially increased responding in monkeys under shock avoidance schedules, but these effects diminished with repeated exposure. Serotonin antagonists blocked DOB-induced decreases in food-seeking behavior.
Area of Science:
- Pharmacology
- Neuroscience
- Behavioral Science
Background:
- The hallucinogenic drug (+/-)-4-bromo-2,5-dimethoxyamphetamine HCl (DOB) is a potent psychoactive substance.
- Serotonin (5-HT) receptors, particularly the 5-HT2 subtype, are implicated in the effects of hallucinogens.
- Understanding the behavioral effects and receptor interactions of DOB is crucial for psychopharmacological research.
Purpose of the Study:
- To investigate the behavioral effects of DOB in squirrel monkeys under different operant schedules.
- To determine the role of serotonin receptors in mediating the effects of DOB.
- To examine the temporal dynamics and potential tolerance development to DOB's actions.
Main Methods:
- Squirrel monkeys were trained on fixed-interval (FI) schedules of food presentation and shock avoidance (SA) schedules.
- DOB was administered intravenously at doses ranging from 0.003 to 0.3 mg/kg.
- The effects of DOB were assessed on response rates, and antagonist effects of ketanserin, methysergide, and mianserin were evaluated.
Main Results:
- Under FI schedules, DOB produced dose-dependent decreases in responding, which were antagonized by 5-HT2 and non-selective 5-HT antagonists.
- Initially, DOB increased responding under SA schedules, but these rate-increasing effects diminished with repeated administration in a complex pattern.
- Tolerance to the rate-increasing effects of DOB developed, with some doses eventually causing suppression of responding.
Conclusions:
- The decreases in responding induced by DOB under FI schedules are mediated by 5-HT2 receptor activation.
- Repeated administration of DOB leads to a rapid development of tolerance to its rate-increasing effects under SA schedules.
- These findings highlight the complex receptor interactions and adaptive mechanisms involved in the behavioral effects of hallucinogenic drugs.