Dopamine agonists prevent or counteract the suppression of brain stimulation reward by fenfluramine.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
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Division of Biology, California Institute of Technology, Pasadena 91125.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004567:Electrodes, Implanted; D005277:Fenfluramine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D010891:Piribedil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*
D018491:Dopamine Agonists; D005277:Fenfluramine; D000661:Amphetamine; D010891:Piribedil