Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice.
We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) has antidepressive-like activity. The aim of the present study was to examine (i) whether caffeic acid, a major metabolite of rosmarinic acid, also has antidepressive-like activity, and (ii) whether these substances inhibit either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity. Rosmarinic acid (2 mg/kg, i.p.) and caffeic acid (4 mg/kg, i.p.) each significantly reduced the duration of immobility in the forced swimming test in mice. In contrast, neither substance, at doses that produced a significant reduction in the immobile response in the forced swimming test, affected spontaneous motor activity. These results indicate that, like rosmarinic acid, caffeic acid also possesses antidepressive-like activity. In neuropharmacological studies, neither rosmarinic acid (10 x (-9)-10 x (-3) M) nor caffeic acid (10 x (-9)-10 x (-3) M) affected either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity in the mouse brain. These results suggest that both caffeic acid and rosmarinic acid may produce antidepressive-like activity via some mechanism(s) other than the inhibition of monoamine transporters and monoamine oxidase.
Takeda
Hiroshi
H
Department of Pharmacology and Intractable Diseases Research Center (Division of Drug Research and Devlopment), Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, 160-8402, Tokyo, Japan. ht0417@tokyo-med.ac.jp
Tsuji
Minoru
M
Inazu
Masato
M
Egashira
Toru
T
Matsumiya
Teruhiko
T
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D053630:Depsides; D004298:Dopamine / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013550:Swimming / Q000523:psychology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D000097123:Rosmarinic Acid
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D002109:Caffeic Acids; D002934:Cinnamates; D053630:Depsides; D004298:Dopamine; D008995:Monoamine Oxidase; D009638:Norepinephrine; D012701:Serotonin; D000097123:Rosmarinic Acid; C040048:caffeic acid