Administration of D,L-fenfluramine to rats produces learning deficits in the Cincinnati water maze but not the Morris water maze: relationship to adrenal cortical output.
Fenfluramine (FEN) is an amphetamine derivative with anorectic properties similar to amphetamine, but without the stimulatory or abuse potential. Administration of FEN produces an immediate release of serotonin as well as inhibits reuptake; ultimately FEN produces a decrease in serotonin stores in the central nervous system. We have previously shown that the administration of FEN to rats results in increased adrenal cortical hormones under resting conditions, without simultaneous elevations in adrenocorticotropin hormone (ACTH). We hypothesized that the adrenal output would be altered following stress and that the altered adrenal output would affect learning and memory, since the adrenal hormones influence learning and memory capability. In this series of experiments, we administered D,L-FEN (15 mg/kg) four times every 2 h on a single day to rats and investigated the effect on hormonal output following forced swim and the effect on sequential learning in the Cincinnati water maze and spatial learning in the Morris maze beginning 3 days after FEN administration. Animals that received FEN had increased corticosterone and aldosterone titers following forced swim relative to control animals, although no differences in ACTH or testosterone were noted. Animals exposed to FEN had lasting deficits in the Cincinnati water maze but not in the Morris water maze, regardless of testing order. These deficits in the Cincinnati water maze appear to be mediated by the elevation in adrenal output since adrenalectomy abolished the effect of FEN. Corticosterone levels were shown to be elevated during the behavioral testing period in animals exposed to FEN.
Williams
Michael T
MT
Division of Developmental Biology, Children's Hospital Research Foundation and University of Cincinnati College of Medicine, 3333 Burnet Avenue, OH 45229-3039, USA.
Morford
LaRonda L
LL
McCrea
Anne E
AE
Wood
Sandra L
SL
Vorhees
Charles V
CV
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000450:Aldosterone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005277:Fenfluramine / Q000009:adverse effects*; D007859:Learning Disabilities / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D013312:Stress, Physiological / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000450:Aldosterone; D003345:Corticosterone; D005277:Fenfluramine; D017367:Selective Serotonin Reuptake Inhibitors