Effects of (+/-) 3,4-methylene-dioxymethamphetamine (ecstasy) on dopamine system function in humans.
Twelve (+/-) 3,4-methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse (group A), and 12 control subjects (group B) were included in the study. Prolactin (PRL) and growth hormone (GH) responses to the dopaminergic agonist bromocriptine (BROM) and psychometric measures were evaluated 3 weeks after MDMA discontinuation. PRL decreased both in A and B subjects after BROM suppression, without any significant difference between the two groups. PRL responses to BROM in MDMA users were in the normal range. In contrast, GH responses to BROM stimulation were found significantly reduced in ecstasy users, in comparison with control subjects (P < 0.001; F = 6.26). MDMA users showed higher scores on the Novelty Seeking (NS) scale at the Three dimensional Personality Questionnaire (TPQ), on direct aggressiveness subscale at Buss Durkee Hostility Inventory (BDHI), on subscale D (depression) at Minnesota Multiphasic Personality Inventory (MMPI 2) and on Hamilton Depression Rating Scale (HDRS) than control subjects. PRL areas under the curves (AUCs) showed a significant inverse correlation with NS scores both in A and B subjects. GH AUCs directly correlated with NS scores in healthy subjects, but not in MDMA users. No other psychometric measure correlated with hormonal responses. GH AUCs were inversely correlated with the measures of MDMA exposure (r = -0.48; P < 0.01). Lower GH response to BROM in A subjects (MDMA users) could reflect reduced D2 receptor sensitivity in the hypothalamus, possibly due to increased intrasynaptic dopamine concentration. Although the hypothesis of dopaminergic changes associated with a premorbid condition cannot be completely excluded, the inverse correlation between DA receptors sensitivity and the extent of ecstasy exposure may suggest a direct pharmacological action of MDMA on brain dopamine function in humans.
Centro Studi Farmacotossicodipendenze, SerT, AUSL di Parma, Via Spalato 2, 43100 Parma, Italy. behpharm@tin.it
Gilberto
G
Gerra
Amir
A
Zaimovic
Gabriele
G
Moi
Francesca
F
Giusti
Simona
S
Gardini
Roberto
R
Delsignore
Gianni
G
Laviola
Teodora
T
Macchia
Francesca
F
Brambilla
D000293:Adolescent; D000328:Adult; D000374:Aggression / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D003866:Depressive Disorder / Q000139:chemically induced / Q000523:psychology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006213:Hallucinogens / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D010551:Personality / Q000187:drug effects; D010556:Personality Tests; D011388:Prolactin / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects*; D019966:Substance-Related Disorders / Q000523:psychology*; D013694:Temperament / Q000187:drug effects
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D006213:Hallucinogens; D017448:Receptors, Dopamine D2; D019382:Human Growth Hormone; D001971:Bromocriptine; D011388:Prolactin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine