DIFFERENTIAL REGULATION BY METHYLENEDIOXYMETHAMPHETAMINE OF 5-HYDROXYTRYPTAMINE(1A) RECEPTOR DENSITY AND MESSENGER-RNA EXPRESSION IN RAT HIPPOCAMPUS, FRONTAL-CORTEX, AND BRAIN-STEM - THE ROLE OF CORTICOSTEROIDS

The present study examined the effects of repeated administration to r ats of 3,4-methylenedioxymethamphetamine (MDMA, ''Ecstasy'') on 5-hydr oxytryptamine(1A) (5-HT1A) receptor density and mRNA expression in the hippocampus, frontal cortex, and brainstem. As expected, 7 days after subacute MDMA administration (20 mg/kg i.p. twice daily for 4 consecu tive days) 5-HT content was markedly reduced (-70%) in the hippocampus and the frontal cortex. 5-HT1A receptor density was increased in the frontal cortex by 23% and decreased in the hippocampus and the brainst em by 25%. These changes correlated with an enhanced or diminished 5-H T1A receptor mRNA expression in the three regions studied. To examine the influence of corticosteroids on these changes, adrenalectomized (A DX) rats received the same dosage regimen as above. Adrenalectomy by i tself did not modify 5-HT content in the brain regions examined and in creased 5-HT1A receptor density in the hippocampus (+20%) but produced no change in the frontal cortex and brainstem. Adrenalectomy also pre vented MDMA-induced changes in receptor number in the hippocampus and brainstem but not in the frontal cortex. Dexamethasone (1 mg/kg/day i. p.) administered for 7 consecutive days reversed the effects of adrena lectomy in the hippocampus but not in the frontal cortex. In the brain stem, MDMA no longer reduced 5-HT1A receptor number in ADX rats, but a significant reduction was restored when ADX animals received the gluc ocorticoid treatment. The present data show that MDMA may affect 5-HT1 A receptors in a regionally dependent manner, notably through a drug e ffect on corticosterone release, which attenuates 5-HT1A receptor gene transcription selectively in the hippocampus.