期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 84, 期 2, 页码 337-343出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2006.05.022
关键词
serotonin; rhesus monkey; self-administration; stimulants; 5-HT2 receptor
资金
- NIDA NIH HHS [K05-DA15343, DA-10352] Funding Source: Medline
Previous research with psychostimulants has suggested a negative relationship between both potency and efficacy as a reinforcer and serotonergic potency, particularly relative to dopaminergic potency. The present experiment was designed to examine the relationship between the serotonergic activity and efficacy as a reinforcer by allowing rhesus monkeys (n=5) to self-administer amphetamine mixed with a serotonin releaser, fenfluramine. Additionally, the role of 5-HT2 receptors in the interaction between amphetamine and fenfluramine was investigated using ketanserin, a selective 5-HT2 receptor antagonist. Amphetamine and fenfluramine were combined in ratios of, respectively, 1: 1 to 1: 10 on a mg/kg basis and made available for self-administration under a progressive-ratio schedule of reinforcement. Amphetamine (0.0056-0.1 mg/kg/injection) functioned as a positive reinforcer with sigmoidal or biphasic dose-response functions. The addition of fenfluramine to amphetamine decreased the maximum responding, at least at the highest dose ratio (1:10, amphetamine/fenfluramine), in all monkeys. When measured after the pretreatment of ketanserin (1.0-3.0 mg/kg, i.m.), the self-administration of the mixture of amphetamine and fenfluramine at a ratio of 1:10 decreased in three monkeys and was unaffected in the fourth. These results support the notion of a negative influence of increased serotonergic neurotransmission on reinforcing efficacy of drugs that act via monoamine systems. However, the involvement of 5-HT2 receptors in the interaction between the serotonergic system and the reinforcing efficacy still remains equivocal. (c) 2006 Elsevier Inc. All rights reserved.
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