Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum.
Hypericum perforatum is considered an effective alternative to the synthetic antidepressants in the treatment of mild-to-moderate depression. Recently, we showed that the effects on neurotransmitter contents in different brain regions of laboratory animals are more evident after administration of hypericum extracts containing a higher concentration of flavonoids, thus suggesting that these compounds are important in the antidepressant action of hypericum perforatum. We studied the effects of Ph-50, a hypericum extract standardized to flavonoids (50%) and containing 0.3% hypericin and 4.5% hyperforin on brain serotonin content, norepinephrine and dopamine by a high-performance liquid chromatography method in discrete brain areas (cortex, diencephalon and brainstem) in male Sprague-Dawley rats. Moreover, we evaluated the effects of Ph-50 alone or in association with sulpiride (a dopamine receptor antagonist), metergoline (a serotonin receptor antagonist) and 6-hydroxydopamine (6-OH-DA, destroying norepinephrine-containing neurons) using a forced-swimming test in the rat. Hypericum extract (Ph-50; 250-500 mg/kg) with acute oral administration enhanced serotonin, norepinephrine and dopamine content in the brain and reduced the immobility time of rats in the forced-swimming test. Sulpiride, metergoline and 6-OH-DA significantly increased the period of immobility in the forced-swimming test for the rats receiving hypericum extract (Ph-50). The results indicate that the neurotransmitters studied could be involved in the anti-immobility effects of hypericum, and suggest that its antidepressant action is probably mediated by serotonergic, noradrenergic and dopaminergic system activation.
Calapai
G
G
Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica Policlinico Universitario, Italy. gcalapai@unime.it
Crupi
A
A
Firenzuoli
F
F
Inferrera
G
G
Squadrito
F
F
Parisi
A
A
De Sarro
G
G
Caputi
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003863:Depression / Q000523:psychology; D004298:Dopamine / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D020902:Hypericum; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D013563:Sympathectomy, Chemical
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D010936:Plant Extracts; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D013469:Sulpiride; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine