Abstract:
:Rats were trained to discriminate fenfluramine (1.0 mg/kg) from saline in a two-lever drug discrimination task. The dose-response curve for this discrimination was orderly with an ED50 of about one-half of the training dose (0.52 mg/kg). In substitution tests, indirect (p-chloroamphetamine) and direct (quipazine, MK-212, lisuride) serotonin (5-HT) agonists substituted for fenfluramine. Since none of these compounds have been reported to be hallucinogenic and the potent hallucinogen LSD did not substitute completely, it was suggested that the discriminative stimulus properties of fenfluramine are not related to its ability to produce hallucinations in humans. The fenfluramine cue, like the quipazine cue, was antagonized by the 5-HT antagonists cyproheptadine and methiothepin. Unlike quipazine, fenfluramine was also partially antagonized by the 5-HT uptake inhibitor, fluoxetine, and the 5-HT synthesis inhibitor, p-chlorophenylalanine. Thus, the fenfluramine cue differs from that of quipazine in that it is mediated via indirect actions on 5-HT receptors. Since the indirect dopamine (DA) agonist d-amphetamine failed to substitute and the DA antagonist haloperidol failed to block the fenfluramine cue, a mediating role for DA was not indicated. Another indirect DA agonist, cocaine, substituted partially for fenfluramine, a result which paralleled that seen with fluoxetine. Both of these partial substitutions were reduced by cyproheptadine; therefore, it was concluded that these effects may be due to the common ability of cocaine, fluoxetine, and fenfluramine to inhibit 5-HT uptake.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
White FJ,Appel JBdoi
10.1007/BF00429199subject
Has Abstractpub_date
1981-01-01 00:00:00pages
110-5issue
2eissn
0033-3158issn
1432-2072journal_volume
73pub_type
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journal_title:Psychopharmacology
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更新日期:2006-07-01 00:00:00
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更新日期:2013-02-01 00:00:00
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更新日期:2012-04-01 00:00:00
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更新日期:2012-09-01 00:00:00
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