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Dopamine Agonists Prevent or Counteract the Suppression of Brain Stimulation Reward by Fenfluramine

Olds, M. E. (1995) Dopamine Agonists Prevent or Counteract the Suppression of Brain Stimulation Reward by Fenfluramine. Pharmacology Biochemistry and Behavior, 50 (1). pp. 41-48. ISSN 0091-3057. doi:10.1016/0091-3057(94)00240-J.

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The interaction between the serotonin (5-HT) and the dopamine (DA) systems in the modulation of intracranial self-stimulation (ICSS), a DA-dependent behavior, was investigated. Chronically implanted rats for ICSS in the medial forebrain bundle were tested for the effects of fenfluramine at a dose of 20 mg/kg, and then for the effects of 10 mg/kg piribedil plus 2 mg/kg amphetamine, injected 30 min before fenfluramine or 60 min after fenfluramine. Our aim was to determine whether the action of fenfluramine at the DA binding site could be blocked by prior occupation, or whether if it were occupied by fenfluramine it could be reversed. Fenfluramine, 20 mg/kg, injected alone, suppressed ICSS for 5–7 h. The suppression was followed by a prolonged recovery during which ICSS was profounded depressed. Repeating the treatment 7 days later produced the same response, except that the suppression was of shorter duration. In another group of animals, pretreatment with piribedil plus amphetamine 30 min before fenfluramine prevented the suppression of ICSS. Instead, ICSS was briefly attenuated, then restored to baseline levels, and then facilitated. Repeating the treatment 7 days after the first treatment potentiated this response. The attenuation was now even briefer, the recovery more rapid, and the facilitation more robust. In still another group of animals, fenfluramine was given just before the ICSS session began. Predictably, the effect was a total cessation of ICSS. At 60 min into the session, piribedil plus amphetamine was injected. The response showed a rapid recovery of ICSS followed by facilitation. Repeating the treatment 7 days later potentiated this response. Recovery to baseline ICSS was more rapid and facilitation was larger and longer lasting. These results are discussed in terms of a possible neuroleptic-like action of fenfluramine being responsible for a portion of the effects of fenfluramine on ICSS, which suggests a basis for the protection afforded by the DA agonists.

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Additional Information:© 1994 Elsevier Science Ltd. Received 9 September 1993.
Subject Keywords:Amphetamine; Dopamine; Intracranial self-stimulation; Fenfluramine; Piribedil; Serotonin
Issue or Number:1
Record Number:CaltechAUTHORS:20140523-084643477
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Official Citation:M.E. Olds, Dopamine agonists prevent or counteract the suppression of brain stimulation reward by fenfluramine, Pharmacology Biochemistry and Behavior, Volume 50, Issue 1, January 1995, Pages 41-48, ISSN 0091-3057, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:45894
Deposited By: Ruth Sustaita
Deposited On:27 May 2014 16:02
Last Modified:10 Nov 2021 17:17

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