Abstract/Details

Adolescent 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’) exposure in rats: Behavioral, neurochemical, and pharmocokinetic activity


2007 2007

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Abstract (summary)

The drug ±3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational substance among young people. Most prior research has not attempted to carefully emulate human ecstasy use patterns in animal investigations. The objectives of the present series of experiments were to develop a rat model of intermittent ecstasy use and to begin to characterize the acute and long-term physiological, behavioral, and neurochemical consequences of adolescent MDMA exposure. In Experiments I and II, male Sprague-Dawley rats received 20 mg/kg/day of MDMA on every fifth day from postnatal day 35 to 60. This regimen caused subtle reductions in cortical serotonin transporter (SERT) binding and dose dependently modified indices of attention, working memory, and anxiety-like behavior. Experiment III tested whether periadolescent MDMA exposure (10 mg/kg x 2) modified the responses to a MDMA binge (5 or 10 mg/kg x 4) in young adulthood. Adolescent MDMA completely blocked the hypoactivity and SERT reductions induced by adult MDMA treatments. Importantly, developmental MDMA exposure only partially reduced the hyperthermia evoked by the binge. The pharmacokinetic profile of early (PD 35) and late (PD 60) adolescent MDMA (10 mg/kg) treatments were compared in Experiment IV. Pharmacokinetic parameters (elimination half-life, peak concentration) did not differ by age for MDMA but PD 60 animals showed lower peak concentrations of the metabolite methylenedioxyamphetamine (MDA). Finally, the goal of Experiment V was to determine if MDMA induced decreases in SERT levels mediated the behavioral consequences. Rats received the binge (10 mg/kg x 4) in combination with pretreatment with the serotonin reuptake inhibitor citalopram (10 mg/kg). Citalopram blocked SERT reductions measured one week after dosing and prevented some of the MDMA induced alterations in complex behavior. These studies reveal that: (1) repeated exposure to a clinically relevant MDMA dose can reduce cognitive function and alter affective behavior, (2) adolescent MDMA can lead to MDMA tolerance in adulthood, (3) the behavioral toxicology of MDMA may not be exclusively mediated by decreases in SERT. Overall, these findings indicate that the enduring neurobiological consequences of MDMA may not be limited to the serotonergic system and have substantial public health implications for regular ecstasy users.

Keywords. Adolescence, Behavior, Memory, Serotonin transporter, Temperature, Weight

Indexing (details)


Subject
Neurology;
Pharmacology;
Physiological psychology
Classification
0317: Neurology
0419: Pharmacology
0989: Physiological psychology
Identifier / keyword
Health and environmental sciences; Psychology; Biological sciences; Adolescents; Ecstasy; MDMA; Serotonin
Title
Adolescent 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’) exposure in rats: Behavioral, neurochemical, and pharmocokinetic activity
Author
Piper, Brian James
Number of pages
172
Publication year
2007
Degree date
2007
School code
0118
Source
DAI-B 68/02, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
Advisor
Meyer, Jerrold S.
University/institution
University of Massachusetts Amherst
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3254963
ProQuest document ID
304846809
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304846809
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