Address for correspondence: Jerrold S. Meyer, Ph.D., Department of Psychology, Tobin Hall, University of Massachusetts, Amherst, MA 01003. Voice: 413-545-2168; fax: 413-545-0996.
jmeyer{at}psych.umass.edu
Ann. N.Y. Acad. Sci. 965: 373-380 (2002).
The abused drug 3,4-methylenedioxymethamphetamine (MDMA) damages
fine serotonergic fibers and nerve terminals in adult organisms;
however, developing animals seem less susceptible to this effect.
One proposed hypothesis is that neonates are less sensitive
to MDMA neurotoxicity because they fail to show drug-induced
hyperthermia. We tested this hypothesis by producing hyperthermia
in neonatal rats for 2 hours after each of twice-daily MDMA
(10 mg/kg sc) or saline injections given over the period from
postnatal day (PD) 1 to 4. Other drug-treated and control litters
were maintained at normothermic temperatures after injection.
Differential core body temperatures were achieved by placing
pups (without the dam) in humidified, thermostatically controlled
incubators. Temperatures were monitored with a thermocouple
probe at 30-minute intervals. Pups subsequently remained undisturbed
until sacrifice at PD 25 and PD 60 for assessment of serotonergic
damage by measuring 5-HT transporter (SERT) binding in the hippocampus
and neocortex as well as 5-HT and 5-HIAA concentrations (PD
25 only). Neonatal MDMA exposure led to significant reductions
in both SERT binding and 5-HT levels in the hippocampus at PD
25, independent of body temperature during treatment. Hippocampal
SERT binding increased between PD 25 and PD 60 in both the MDMA
and saline groups, but the MDMA-related deficit remained unchanged.
Interestingly, the neocortex showed no effect of MDMA at PD
25, but SERT binding was significantly reduced at PD 60. Thus,
MDMA can exert serotonergic neurotoxicity in developing animals
in the absence of elevated body temperature. Hippocampal serotonergic
innervation is damaged early, whereas neocortical effects emerge
at a later time. Furthermore, the tendency for serotonergic
recovery may be less after neonatal MDMA exposure than exposure
of adult animals.
