The relationship between serotonin (5-HT) function on anxiety in rats is examined in this brief review. The author reports that p-chlorophenylalanine and 5,7-dihydroxytryptamine (5,7-DHT) induced serotonin (5-HT) depletion are generally anxiolytic, but that a notable minority of papers reports anxiogenesis after these 5-HT depleting treatments. The authors hypothesize that moderate depletion in 5-HT may effect anxiety more than severe depletion. Noting that Dark Agouti rats are more anxious than Wistar (or Sprague-Dawley) rats, as indicated by baseline performance on the elevated plus maze, the author suggests that MDMA neurotoxicity may increase anxiety in a less anxious strain and reduce anxiety in a more anxious strain (see Gurtman et al 2002; Mechan 2002; Morley 2002). However, increased anxiety in Lister hooded rats given a non-neurotoxic dose of MDMA (Fone et al. 2002) further indicates that some MDMA-mediated changes in anxiety may be due to changes in neural function, and not changes in 5-HT transmission per se. While the relevance of these findings in humans is briefly addressed, the authors do not examine human clinical trials or studies in ecstasy users, and give some indication of not understanding that proposed use of MDMA in therapy does not involve daily dosing and does not rest on acute drug effects alone.
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