期刊
PSYCHOPHARMACOLOGY
卷 232, 期 6, 页码 1039-1047出版社
SPRINGER
DOI: 10.1007/s00213-014-3739-3
关键词
Serotonin receptor; Drug abuse; Drug discrimination; Mouse
资金
- NIGMS IDeA Program award [GM110702]
- UAMS Translational Research Institute [RR029884]
- Lundbeck Foundation
- American Society of Pharmacology and Experimental Therapeutics
2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH) is structurally similar to N-benzyl substituted phenethylamine hallucinogens currently emerging as drugs of abuse. 25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro, but has not been behaviorally characterized. 25CN-NBOH was compared to the traditional phenethylamine hallucinogen R(-)-2,5-dimethoxy-4-iodoamphetamine (DOI) using mouse models of drug-elicited head twitch behavior and drug discrimination. Drug-elicited head twitches were quantified for 10 min following administration of various doses of either DOI or 25CN-NBOH, with and without pretreatments of 0.01 mg/kg 5-HT2A antagonist M100907 or 3.0 mg/kg 5-HT2C antagonist RS102221. The capacity of 25CN-NBOH to attenuate DOI-elicited head twitch was also investigated. Mice were trained to discriminate DOI or M100907 from saline, and 25CN-NBOH was tested for generalization. 25CN-NBOH induced a head twitch response in the mouse that was lower in magnitude than that of DOI, blocked by M100907, but not altered by RS102221. DOI-elicited head twitch was dose-dependently attenuated by 25CN-NBOH pretreatment. 25CN-NBOH produced an intermediate degree of generalization (55 %) for the DOI training dose, and these interoceptive effects were attenuated by M100907. Finally, 25CN-NBOH did not generalize to M100907 at any dose, but ketanserin fully substituted in these animals. 25CN-NBOH was behaviorally active, but less effective than DOI in two mouse models of hallucinogenic effects. The effectiveness with which M100907 antagonized the behavioral actions of 25CN-NBOH strongly suggests that the 5-HT2A receptor is an important site of agonist action for this compound in vivo.
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