Intermittent prenatal MDMA exposure alters physiological but not mood related parameters in adult rat offspring.
The recreational party drug "ecstasy" (3,4-methylenedioxymethamphetamine MDMA) is particularly popular among young adults who are in the childbearing age and thus there is a substantial risk of prenatal MDMA exposure. We applied an intermittent treatment protocol with an early first injection on pregnant Wistar rats (15 mg/kg MDMA s.c. on the E4, E11 and E18 days of gestation) to examine the potential physiological, endocrine and behavioral effects on adult male and female offspring. Prenatal MDMA-treatment provoked reduced body weight of offspring from the birth as far as the adulthood. Adult MDMA-offspring had a reduced blood-glucose concentration and hematocrit, altered relative spleen and thymus weight, had lower performance on wire suspension test and on the first trial of rotarod test. In contrast, no alteration in the locomotor activity was found. Anxiety and depression related behavioral parameters in elevated plus maze, sucrose preference or forced swimming tests were normal. MDMA-offspring had elevated concentration of the ACTH-precursor proopiomelanocortin and male MDMA-offspring exhibited elevated blood corticosterone concentration. No significant alteration was detected in the serotonergic marker tryptophan-hydroxylase and the catcholaminergic marker tyrosine-hydroxylase immunoreactive fiber densities in MDMA-offspring. The mothers exhibited reduced densities of serotonergic but not catecholaminergic fibers after the MDMA treatment. Our findings suggest that an intermittent prenatal MDMA exposure with an early first injection and a relatively low cumulative dose provokes mild but significant alterations in physical-physiological parameters and reduces motor skill learning in adulthood. In contrast, these adult offspring do not produce anxiety or depression like behavior.
Department of Pharmacodynamics, Semmelweis University, H-1085, Budapest, Nagyvárad tér 4, Hungary.
Csaba
C
Adori
Dóra
D
Zelena
Júlia
J
Tímár
Zsuzsa
Z
Gyarmati
Agnes
A
Domokos
Melinda
M
Sobor
Zsuzsanna
Z
Fürst
Gábor
G
Makara
György
G
Bagdy
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D003342:Corpus Striatum / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006400:Hematocrit; D006624:Hippocampus / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D009048:Motor Skills / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test; D013037:Spatial Behavior / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000254:growth & development; D013950:Thymus Gland / Q000187:drug effects / Q000254:growth & development; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001786:Blood Glucose; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003345:Corticosterone