Learning and memory after neonatal exposure to 3,4-methylenedioxymethamphetamine (ecstasy) in rats: interaction with exposure in adulthood.
This study determined whether developmental and adult 3,4-methylenedioxymethamphetamine (MDMA) exposures in rats have interactive effects on body temperature, learning, other behaviors, and monoamine concentrations in the hippocampus, prefrontal cortex, and striatum. Learning was assessed in the Cincinnati water maze (CWM), Morris water maze (MWM), and novel object recognition (NOR). On acquisition trials in the MWM, significant differences from developmental MDMA exposure were found on latency, cumulative distance, path length, and angle of first bearing to the goal, but the early and adult MDMA exposure group performed no worse than the developmental-only MDMA group. In the reversal trials, however, an interaction was seen: latency to the goal, cumulative distance, and angle of first bearing were increased in animals treated both developmentally and in adulthood with MDMA compared with those treated only developmentally. Other tests (elevated zero maze, CWM, NOR, and open-field activity) did not show an interaction, nor did hippocampal concentrations of serotonin or dopamine. However, several behavioral tests showed neonatal MDMA effects, including increased errors in the CWM, reduced time spent with a new object in the NOR test, and reduced locomotor activity in the open-field. By contrast, adult MDMA decreased the number of entries into open quadrants of the elevated zero maze. Litter effects were controlled by treating litter as the experimental unit and using mixed models repeated measures analyses. Correlational analyses suggested that the MWM reversal interaction involves multiple monoamine changes. The results indicate that developmental MDMA exposure can interact with adult exposure to interfere with some aspects of learning.
Cohen
Martha A
MA
Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039, USA.
Skelton
Matthew R
MR
Schaefer
Tori L
TL
Gudelsky
Gary A
GA
Vorhees
Charles V
CV
Williams
Michael T
MT
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004924:Escape Reaction / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D006213:Hallucinogens / Q000633:toxicity*; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects; D013223:Statistics as Topic; D013997:Time Factors
D015306:Biogenic Monoamines; D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine