Hypothalamic-pituitary-adrenal axis responses to stress in subjects with 3,4-methylenedioxy-methamphetamine ('ecstasy') use history: correlation with dopamine receptor sensitivity.
Fifteen 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') users who did not have other drug dependencies or prolonged alcohol abuse and 15 control subjects were studied. All the subjects were exposed to the same psychosocial stressor (Stroop Color-Word Interference Task, public speaking and mental arithmetic in front of an audience) 3 weeks after MDMA discontinuation. Plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol were measured immediately before the tests began and at their end, 30 min later. Growth hormone (GH) responses to the dopaminergic agonist bromocriptine and psychometric measures (Tridimensional Personality Questionnaire, Minnesota Multiphasic Personality Inventory, Buss-Durkee Hostility Inventory) were also obtained 4 weeks after MDMA discontinuation for the same subjects. ACTH and cortisol basal levels were significantly higher in ecstasy users than in control subjects. In contrast, ACTH and cortisol responses to stress were significantly blunted in MDMA users. The sensitivity of dopamine D2 receptors, reflected by GH responses to bromocriptine challenge, was reduced in MDMA users compared with controls. The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis (ACTH and cortisol delta peaks) correlated directly with GH areas under curves in response to bromocriptine, and inversely with psychometric measures of aggressiveness and novelty seeking. No correlation was found between hormonal measures and the extent of MDMA exposure. Reduced D2 receptor sensitivity, HPA basal hyperactivation and reduced responsiveness to stress may represent a complex neuroendocrine dysfunction associated with MDMA use. The present findings do not exclude the possibility that dopamine dysfunction partly predated MDMA exposure.
Gerra
Gilberto
G
Addiction Research Centre, Centro Studi Farmacotossicodipendenze, SerT, AUSL, Via Spalato 2, Parma 43100, Italy. g.gerra@palazzochigi.it
Bassignana
Sara
S
Zaimovic
Amir
A
Moi
Gabriele
G
Bussandri
Monica
M
Caccavari
Rocco
R
Brambilla
Francesca
F
Molina
Enzo
E
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D001971:Bromocriptine / Q000494:pharmacology; D003071:Cognition / Q000502:physiology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D006727:Hormone Antagonists / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009483:Neuropsychological Tests; D010555:Personality Inventory; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000378:metabolism* / Q000523:psychology; D011795:Surveys and Questionnaires
D006727:Hormone Antagonists; D011954:Receptors, Dopamine; D019382:Human Growth Hormone; D001971:Bromocriptine; D000324:Adrenocorticotropic Hormone; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D006854:Hydrocortisone