Repeated adolescent MDMA ("Ecstasy") exposure in rats increases behavioral and neuroendocrine responses to a 5-HT2A/2C agonist.
MDMA (3,4-methylenedioxymethamphetamine) is a popular recreational drug among adolescents. The present study aimed to determine the effects of repeated intermittent administration of 10 mg/kg MDMA during adolescence on behavioral (Experiment 1) and neuroendocrine (Experiment 2) responses of rats to the 5-HT(2A/2C) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and on [(3)H]ketanserin binding to 5-HT(2A) receptors. In the first experiment, MDMA pretreatment increased the frequency of head twitches and back muscle contractions, but not wet-dog shakes, to a high-dose DOI challenge. In the second experiment, both the prolactin and corticosterone responses to DOI were potentiated in MDMA-pretreated animals. No changes were found in 5-HT(2A) receptor binding in the hypothalamus or other forebrain areas that were examined. These results indicate that intermittent adolescent MDMA exposure enhances sensitivity of 5-HT(2A/2C) receptors in the CNS, possibly through changes in downstream signaling mechanisms.
Biezonski
Dominik K
DK
Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003-7710, USA.
Courtemanche
Andrea B
AB
Hong
Sang B
SB
Piper
Brian J
BJ
Meyer
Jerrold S
JS
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D009490:Neurosecretory Systems / Q000187:drug effects*; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D018490:Serotonin Agents / Q000494:pharmacology
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D018490:Serotonin Agents; D011388:Prolactin; D007650:Ketanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone