Region-dependent effects of acute and chronic tranylcypromine in vivo on [3H]2-BFI binding to brain imidazoline I(2) sites.

An imidazoline I(2) site has been localised to monoamine oxidase. However, in vitro studies of the effect of monoamine oxidase inhibitors on imidazoline I(2)-site radioligand binding have produced conflicting findings. Using the technique of autoradiography, we examined the effect of in vivo administration of the irreversible monoamine oxidase inhibitor tranylcypromine on binding of the imidazoline I(2) site-specific ligand [3H]2-(-2-benzofuranyl)-2-imidazoline ([3H]2-BFI) in four rat brain nuclei which are known to possess a high density of imidazoline I(2) sites, together with cerebral cortex and cerebellum which show weaker binding. A single acute pre-treatment with tranylcypromine significantly increased imidazoline I(2) site-specific binding in four regions: arcuate nucleus, interpeduncular nucleus, pineal gland and area postrema, but effects in cortical areas and cerebellum were not significant. The extent of the increase was proportional to the control binding in each region. In contrast, five daily treatments with the same dose of tranylcypromine significantly reduced [3H]2-BFI binding in these same areas. The potential role of monoamine oxidase isoforms in these changes is discussed.

Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms.

Previous work has indicated recreational use of methylenedioxymethamphetamine (MDMA or ecstasy) is associated with elevated scores on self-report measures of depression. We sought to examine the long-term effects of consumption on depression in a group of individuals who had consumed large quantities of the drug in the past, but were now leading relatively drug free lives. Respondents to this study (n = 29) had consumed an average of 1.5 ecstasy tablets in the last month, 8.4 in the last 6 months and 23.3 in the last 12 months. The estimated total consumed was 527 tablets, indicating that these respondents were indeed former chronic users of the drug. None of the respondents had consumed ecstasy in the last 14 days. Levels of depression (Beck's Depression Inventory) were significantly (p < 0.01) elevated compared to a matched non-drug using control group. Within the group of former chronic users, these levels of depression were not significantly affected by current use of alcohol, cannabis or amphetamine, but were positively correlated with an external locus of control (p < 0.05), infrequent but severe- (p < 0.05) and frequent but mild- (p < 0.005) self-report measures of life stress. Multiple regression indicated that levels of frequent but mild life stress (p < 0.005) and the quantity of ecstasy tablets respondents consumed over a 12-h period (p < 0.05) were the only variables that were significant predictors of self-reported levels of depression. The results of this study indicate that former chronic ecstasy users report higher levels of depression than their matched controls.