Altered forebrain neurotransmitter responses to immobilization stress following 3,4-methylenedioxymethamphetamine
Section snippets
Animals
Male Sprague–Dawley rats (175–250 g) were purchased from Zivic Miller Labs (Allison Park, PA, USA). Rats were housed individually, with food and water available ad libitum, on a 12-h light–dark cycle in a temperature controlled room. All procedures were in adherence to the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) and approved by the local institutional animal care committee.
Drugs
All rats were given i.p. injections with 10 mg/kg MDMA
Neurochemical content of monoamines
Serotonin tissue content of rats treated with MDMA was significantly decreased by 55% in the dorsal hippocampus (t(28)=6.28, P<0.01) and 48% in the frontal cortex (t(28)=3.09, P<0.01) compared to saline treated rats (Table 1). There was no effect of MDMA pretreatment on the concentration of dopamine in the frontal cortex (t(26)=0.674).
Extracellular serotonin response to stress
In the dorsal hippocampus, there was a significant difference between the treatment groups in 5-HT concentrations throughout the experiment as indicated by the
MDMA pretreatment attenuates stress-induced neurotransmitter release
The primary, novel finding of the current study is that MDMA pretreatment can inhibit acute 5-HT and dopamine responses to a behavioral challenge, i.e. immobilization stress. The attenuated 5-HT responsiveness is consistent with previous studies using less subtle pharmacological challenges that activate striatal and cortical 5-HT systems (Series et al., 1994, Shankaran and Gudelsky, 1999). A similar attenuation of 5-HT release following a pharmacological challenge has also been reported
Overall conclusions
Pretreatment with MDMA resulted in 5-HT tissue depletions in the hippocampus and the frontal cortex. MDMA pretreatment blunted the dopamine and 5-HT increases during acute immobilization stress observed in non-depleted or saline pretreated rats. While previous studies have shown that the release of 5-HT in response to a pharmacological agent may be impaired by MDMA pretreatment, the present study indicates that the release of neurotransmitters induced by an environmental change (i.e. stress)
Acknowledgements
This work was supported by the National Institutes of Health DA07606, DA07427, DA05837 and AA10760, the Department of Defense DAMD 17-99-1-9479, and the Department of Veterans Affairs.
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Present address: Boston University Medical School, Department of Pharmacology, Boston, MA 02118, USA.