Monoamine reuptake inhibition and mood-enhancing potential of a specified oregano extract

A healthy, balanced diet is essential for both physical and mental well-being. Such a diet must include an adequate intake of micronutrients, essential fatty acids, amino acids and antioxidants. The monoamine neurotransmitters, serotonin, dopamine and noradrenaline, are derived from dietary amino acids and are involved in the modulation of mood, anxiety, cognition, sleep regulation and appetite. The capacity of nutritional interventions to elevate brain monoamine concentrations and, as a consequence, with the potential for mood enhancement, has not been extensively evaluated. The present study investigated an extract from oregano leaves, with a specified range of active constituents, identified via an unbiased, high-throughput screening programme. The oregano extract was demonstrated to inhibit the reuptake and degradation of the monoamine neurotransmitters in a dose-dependent manner, and microdialysis experiments in rats revealed an elevation of extracellular serotonin levels in the brain. Furthermore, following administration of oregano extract, behavioural responses were observed in mice that parallel the beneficial effects exhibited by monoamine-enhancing compounds when used in human subjects. In conclusion, these data show that an extract prepared from leaves of oregano, a major constituent of the Mediterranean diet, is brain-active, with moderate triple reuptake inhibitory activity, and exhibits positive behavioural effects in animal models. We postulate that such an extract may be effective in enhancing mental well-being in human

The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') to rats

1. The pharmacology of the acute hyperthermia that follows 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') administration to rats has been investigated. 2. MDMA (12.5 mg kg(−1) i.p.) produced acute hyperthermia (measured rectally). The tail skin temperature did not increase, suggesting that MDMA may impair heat dissipation. 3. Pretreatment with the 5-HT(1/2) antagonist methysergide (10 mg kg(−1)), the 5-HT(2A) antagonist MDL 100,907 (0.1 mg kg(−1)) or the 5-HT(2C) antagonist SB 242084 (3 mg kg(−1)) failed to alter the hyperthermia. The 5-HT(2) antagonist ritanserin (1 mg kg(−1)) was without effect, but MDL 11,939 (5 mg kg(−1)) blocked the hyperthermia, possibly because of activity at non-serotonergic receptors. 4. The 5-HT uptake inhibitor zimeldine (10 mg kg(−1)) had no effect on MDMA-induced hyperthermia. The uptake inhibitor fluoxetine (10 mg kg(−1)) markedly attenuated the MDMA-induced increase in hippocampal extracellular 5-HT, also without altering hyperthermia. 5. The dopamine D(2) antagonist remoxipride (10 mg kg(−1)) did not alter MDMA-induced hyperthermia, but the D(1) antagonist SCH 23390 (0.3 – 2.0 mg kg(−1)) dose-dependently antagonized it. 6. The dopamine uptake inhibitor GBR 12909 (10 mg kg(−1)) did not alter the hyperthermic response and microdialysis demonstrated that it did not inhibit MDMA-induced striatal dopamine release. 7. These results demonstrate that in vivo MDMA-induced 5-HT release is inhibited by 5-HT uptake inhibitors, but MDMA-induced dopamine release may not be altered by a dopamine uptake inhibitor. 8. It is suggested that MDMA-induced hyperthermia results not from MDMA-induced 5-HT release, but rather from the increased release of dopamine that acts at D(1) receptors. This has implications for the clinical treatment of MDMA-induced hyperthermia