| Title | Self-administration of mixtures of fenfluramine and amphetamine by rhesus monkeys. | | Author(s) | Wee S, Woolverton WL | | Institution | Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, United States. | | Source | Pharmacol Biochem Behav 2006 Jul 7. | | Abstract | 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-HT(2) receptors in the interaction between amphetamine and fenfluramine was investigated using ketanserin, a selective 5-HT(2) 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-HT(2) receptors in the interaction between the serotonergic system and the reinforcing efficacy still remains equivocal. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 16828855 |
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