Discriminative stimulus properties of fenfluramine: Evidence for serotonergic involvement

Mcelroy, J; Feldman, Robert S.

doi:10.1007/bf00429730

Cited by 39 publications

(14 citation statements)

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“…Discriminations have been reported with FEN (White and Appel 1981;McElroy and Feldman 1984), and the failure of amphetamine to generalise and the lack of e¤ect of haloperidol pretreatment suggests little involvement of dopamine in the FEN cue. Discriminations based on PHEN have not been examined, although generalisation of PHEN to other drugs has been tested.…”

Section: Discussionmentioning

confidence: 95%

“…Evidence with amphetamine, a drug with a pharmacological proÞle similar to PHEN indirectly conÞrms the dissimilarity between these two class of drugs. In most cases where comparisons have been made, the discriminative stimulus e¤ects of amphetamine and FEN have been found to be dissimilar (Schechter and Rosecrans 1973;McKenna and Ho 1980;White and Appel 1981;McElroy and Feldman 1984). Human behavioural pharmacological assessments of the dependence producing e¤ects of FEN (Gri¦th et al 1975;Pinder et al 1975;Chait et al 1986) indicate that they are unlikely to be abused.…”

Section: Introductionmentioning

confidence: 94%

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Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats

et al. 1997

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Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0-2.0 mg/kg i.p.) or PHEN (1.0-2.0 mg/kg i.p.) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg i.p.) alone, (2) PHEN (1.0 mg/kg i.p.) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, i.p.) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3-10.0 mg/kg i.p.), amphetamine (0.1-3.0 mg/kg i.p.) and nicotine (0.1-0.8 mg/kg s.c.) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 94%

Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats

et al. 1997

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“…70 Partial substitution has been observed with LSD69 and cocaine.6y ( -)-Fenfluramine did not generalize to ( + )-amphetamine.6y…”

Section: Young and Glennonmentioning

confidence: 91%

“…70 Again, the term stereoselective would be more appropriate. That is, in rats trained to discriminate ( 2 )-fenfluramine from saline, both individual isomers were recognized (i. e. stimulus generalization occurred) ( + )-fenfluramine being slightly more potent than ( -)-fenfl~rarnine.…”

Section: Young and Glennonmentioning

confidence: 99%

Discriminative stimulus properties of amphetamine and structurally related phenalkylamines

Young¹,

Glennon

1986

Medicinal Research Reviews

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“…Drug discrimination procedures have recently been used to examine the role of 5-HT in the behavioral effects of several compounds including fenfluramine (McElroy and Feldman 1984;White and Appel 1981), 1-5-hydroxytryptophan (Barrett et al 1982;Cunningham et al 1985a;Friedman et al 1983), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT; Cunningham et al 1985 b), lysergic acid diethylamide (LSD; Colpaert etal. 1982;Nielsen etal.…”

mentioning

confidence: 99%

Discriminative stimulus properties of the serotonin agonist MK 212

1986

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In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT1/5-HT2 antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT2 antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT1/5-HT2 but not by selective 5-HT2, antagonists suggests the possibility that 5-HT1 receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.

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Discriminative stimulus properties of fenfluramine: Evidence for serotonergic involvement

Cited by 39 publications

References 30 publications

Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats

Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats

Discriminative stimulus properties of amphetamine and structurally related phenalkylamines

Discriminative stimulus properties of the serotonin agonist MK 212

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