Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPgammaS binding in adult rats.
Recreational use of methylenedioxymethamphetamine (MDMA) has dramatically increased among juveniles and young adults of child-bearing age, and the potential for fetal exposure has increased. For this reason, it is surprising that comparatively few studies have assessed the long-term impact of early MDMA exposure on serotonin (5-HT) and dopamine (DA) neurotransmitter systems. The purpose of this study was to determine whether repeated exposure to MDMA during the preweanling period would cause long-term changes in 5-HT and DA functioning. Rats were treated with saline or 20 mg/kg MDMA (two injections per day) from postnatal day (PD) 11-20. At PD 90, rats were killed, and their dorsal striatum, prefrontal cortex, and hippocampus were removed. 5-HT and DA content, as well as their metabolites, were measured using HPLC. In addition, cAMP-dependent protein kinase A (PKA) activity and agonist-stimulated [35S]GTPgammaS binding was assayed using tissue homogenates from each brain region. Results indicated that early MDMA exposure caused a decrease in PKA activity and 5-HT content in the prefrontal cortex and hippocampus while increasing the efficacy of 5-HT1A receptors as measured by agonist-stimulated [35S]GTPgammaS binding. Additionally, DA content was reduced in the dorsal striatum and prefrontal cortex. These data indicate that early MDMA exposure has long-term effects on the 5-HT and DA neurotransmitter systems that may be mediated, at least partially, by changes in 5-HT1A receptor sensitivity.
Crawford
Cynthia A
CA
Department of Psychology, California State University, San Bernardino, CA 92407, USA. ccrawfor@csusb.edu
Williams
Michael T
MT
Kohutek
Jodie L
JL
Choi
Fiona Y
FY
Yoshida
Shelly T
ST
McDougall
Sanders A
SA
Vorhees
Charles V
CV
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D006213:Hallucinogens / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012737:Sex Factors
D006213:Hallucinogens; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D017868:Cyclic AMP-Dependent Protein Kinases; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine