The effects of intracranial administration of hallucinogens on operant behavior in the rat. II. 2,5-Dimethoxy-4-methylamphetamine (DOM).
2,5-Dimethoxy-4-methylamphetamine (DOM) was infused into discrete brain regions of rats trained to press a bar for food reinforcement on a fixed ratio-40 (FR-40). Sites were chosen as major areas of the brain 5-hydroxytryptamine (5-HT) system: the dorsal and median raphe nuclei, dorsal hippocampus, lateral habenular nuclei and the prefrontal cortex. Following training in a fixed ratio-40 (FR-40) operant behavior rats were implanted with stainless steel cannulae into the brain area to be examined. Bilateral cannulae were implanted for the lateral habenular nuclei, dorsal hippocampus and the prefrontal cortex. Following recovery from surgery, DOM (20-300 micrograms) was tested on operant behavior by infusing the drug immediately before the operant session. Infusion of vehicle was inactive. DOM produced a dose-dependent decrease in reinforcements and a concomitant increase in 10-sec periods of non-responding (pause intervals). DOM was more potent when infused into the median raphe nucleus than following intracerebroventricular (ICV) administration. DOM was less potent when infused into the dorsal raphe, prefrontal cortex or dorsal hippocampus. Infusion of DOM into the lateral habenular nuclei produced a biphasic dose-response curve. ED50s for increases in pause intervals were 47, 77, 92, 103, and 114 micrograms for infusion into the median raphe, dorsal raphe, prefrontal cortex, lateral habenulae, and dorsal hippocampus, respectively. The ED50 for ICV administration in a previous study was 58 micrograms. The effects of DOM in the lateral habenulae could be divided into two curves; one curve had an ED50 of 69 micrograms, whereas the other had an ED50 of 176 micrograms. Furthermore, the dose-response curve for IP administration of DOM was shifted to the left in animals with cannulae placed into the lateral habenular nuclei. No change was seen in the response to IP administration of DOM in animals cannulated in the remaining sites or in animals with ICV cannulae. Therefore, the effects of DOM in disrupting operant behavior may be more critical with regard to its actions in the lateral habenulae and median raphe. Nonetheless, actions at multiple brain sites probably contribute to the total behavioral effects of the drug.
Mokler
D J
DJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Stoudt
K W
KW
Sherman
L C
LC
Rech
R H
RH
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000008:administration & dosage*; D000662:Amphetamines / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D008238:Lysergic Acid Diethylamide / Q000008:administration & dosage; D008297:Male; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology
D000662:Amphetamines; D011985:Receptors, Serotonin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D008238:Lysergic Acid Diethylamide