Self-administration of mixtures of fenfluramine and amphetamine by rhesus monkeys.
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.
Wee
Sunmee
S
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.
Woolverton
William L
WL
D000818:Animals; D003913:Dextroamphetamine / Q000008:administration & dosage*; D005277:Fenfluramine / Q000008:administration & dosage*; D007650:Ketanserin / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000502:physiology; D012646:Self Administration
D044348:Receptors, Serotonin, 5-HT2; D005277:Fenfluramine; D007650:Ketanserin; D003913:Dextroamphetamine