Comparison of hypericum extracts with imipramine and fluoxetine in animal models of depression and alcoholism

Clinical evidence suggests that hypericum extracts (Hypericum perforatum L. , St. John's wort) have antidepressive properties and may offer an interest ing alternative for the treatment of mood disorders. In addition, hypericum extracts, as well as standard antidepressants such as the tricyclic, impra mine. and the selective serotonin reuptake inhibitor, fluoxetine, have been reported to be of therapeutic benefit in the treatment of alcoholism as th ese compounds may reduce alcohol craving and/or intake in particular subgro ups of patients. It was the aim of the present study to compare the effects of hypericum extracts with those of imipramine and fluoxetine in the rat f orced swimming test (RFST), a model of depression, as well as in cAA rats, a genetic model of alcoholism. In the RFST, triple i.p. administration of i mipramine (3-30 mg/kg) and fluoxetine (3-30 mg/kg) induced a dose-dependent I-eduction in immobility; the minimal effective dose (MED) being 30 and 10 mg/kg, and the maximal effect being 50% and 57% immobility reduction, for imipramine and fluoxetine, respectively. In this test, the hypericum extrac ts Ze 117 (Remotiv(R)) and LI 160 (Jarsin(R)) also induced a statistically significant reduction of immobility when administered under the same applic ation schedule (5-40 mg/kg, i.p., triple application). In the case of the h ypericum extracts the dose-response relationship was inverted U-shaped with a MED value of 20 mg/kg and a maximal effect of 41% and 32% immobility red uction, fat Ze 117 and LI 160, respectively. Interestingly, the anti-immobi lity effects tended to be more pronounced after subacute ii week, B.I.D.) t reatment with 10 mg/kg of imipramine, fluoxetine, or Ze 117, as compared wi th acute treatment. This phenomenon is in accordance with clinical experien ce and suggests that repeated treatment is required for full development of antidepressive effects. In the alcohol-preferring cAA rats, acute i.p. adm inistration of imipramine (3-30 mg/kg, fluoxetine (1-10 mg/kg) and Ze 117 ( 10-40 mg/kg) dose-dependently reduced alcohol intake in a 12-h limited acce ss two-bottle [ethanol 10% (v/v) versus water] choice procedure; with MED v alues of 30, 5 and 20 mg/kg, respectively. The anti-alcohol effects of fluo xetine and Ze 117 appeared to be specific, as reductions in alcohol intake coincided with reductions in alcohol preference. The present study suggests that hypericum extracts have antidepressant like properties which resemble those of clinically established antidepressants, and that Relnotiv(R) may be an interesting adjunct for the treatment of alcoholism. (C) 1999 Elsevie r Science B.V. All rights reserved.