Evidence of the involvement of the monoaminergic systems in the antidepressant-like effect of Aloysia gratissima.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloysia gratissima (Verbenaceae) is an aromatic plant distributed in South America and, employed in folk medicine for the treatment of nervous systems illness, including depression. The neuroprotective and antidepressant-like activities of the aqueous extract of Aloysia gratissima (AE) administered orally has already been demonstrated.In this study the involvement of monoaminergic systems in the antidepressant-like effect of the AE was investigated. MATERIALS AND METHODS: The implication of the monoaminergic systems in the antidepressant-like activity of Aloysia gratissima was evaluated using different pharmacological antagonists that were administered previously to the acute oral administration of AE (10 mg/kg). The antidepressant-like effect was assessed in the TST and locomotor activity was evaluated in the open-field test in mice. RESULTS: The anti-immobility effect elicited by AE in the TST was prevented by the pre-treatment of mice with the antagonists, NAN-190 (5-HT(1A) receptor), ketanserin (5-HT(2A/2C) receptor), prazosin (α1-adrenoceptor), yohimbine (α2-adrenoceptor), SCH23390 (dopamine D1 receptor), or sulpiride (dopamine D2 receptor). CONCLUSIONS: These results indicate that the antidepressant-like effect of AE in the TST is dependent on its interaction with the serotonergic (5-HT(1A) and 5-HT(2A/2C)), noradrenergic (α1 and α2-adrenoceptors) and dopaminergic (D1 and D2 receptors) systems, suggesting that this specie might act as a new potential resource for developing antidepressants to treat depressive disorders.

Involvement of monoaminergic systems in the antidepressant-like effect of Eugenia brasiliensis Lam. (Myrtaceae) in the tail suspension test in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Several species of Eugenia L. are used in folk medicine for the treatment of various diseases. Eugenia brasiliensis is used for the treatment of inflammatory diseases, whereas Eugenia. uniflora is used for the treatment of symptoms related to depression and mood disorders, and is used in Brazil by the Guarani Indians as a tonic stimulant. AIM OF THE STUDY: To investigate the antidepressant-like effect of hydroalcoholic extracts of different plant species of genus Eugenia and to characterize the participation of the monoaminergic systems in the mechanism of action of the specie that afforded the most prominent antidepressant-like efficacy. MATERIALS AND METHODS: In the first set of experiments, the effects of hydroalcoholic extracts of Eugenia beaurepaireana, Eugenia brasiliensis, Eugenia catharinae, Eugenia umbelliflora and Eugenia uniflora and the antidepressant fluoxetine (positive control) administered acutely by p.o. route were evaluated in the tail suspension test (TST) and locomotor activity was assessed in the open-field test in mice. In the second set of experiments, the involvement of the monoaminergic systems in the antidepressant-like activity of Eugenia brasiliensis was evaluated by treating mice with several pharmacological agonists and antagonists. The effects of the combined administration of sub-effective doses of Eugenia brasiliensis and the antidepressants fluoxetine, imipramine and bupropion were also evaluated. RESULTS: The administration of the extracts from Eugenia brasiliensis, Eugenia catharinae and Eugenia umbelliflora, but not Eugenia beaurepaireana and Eugenia uniflora, exerted a significant antidepressant-like effect, without altering locomotor activity. The behavioral profile was similar to fluoxetine. Pre-treatment of mice with ketanserin, haloperidol, SCH23390, sulpiride, prazosin and yohimbine prevented the reduction of immobility time induced by Eugenia brasiliensis. Treatment with sub-effective doses of WAY100635, SKF38393, apomorphine, phenylephrine, but not clonidine, combined with a sub-effective dose of Eugenia brasiliensis decreased the immobility time in the TST. Furthermore, the combined administration of sub-effectives doses of Eugenia brasiliensis with fluoxetine, imipramine and bupropion produced an antidepressant-like effect. CONCLUSIONS: This study show, for the first time, the antidepressant-like effect of species of the genus Eugenia, especially Eugenia brasiliensis, whose effects in the TST seem to be mediated by serotoninergic (5-HT(1A) and 5-HT(2) receptors), noradrenergic (α(1)-adrenoceptor) and dopaminergic (dopamine D(1) and D(2) receptors) systems.

[Disruption of prepulse inhibition of acoustic startle as an animal model for schizophrenia].

Disruption of prepulse inhibition (PPI) of acoustic startle in rats has been widely used as an animal model for the sensorimotor gating deficit state usually found in schizophrenia. PPI was reported to be regulated by forebrain circuits, including mesolimbic cortex, nucleus accumbens, ventral pallidum, thalamus, and pedunculopontine tegmentum nucleus. Phencyclidine or dopamine agonists, which causes psychotomimetic symptoms in humans, disrupts PPI in animals. The ED50 value of the drugs to reverse the phencyclidine-induced PPI disruption was significantly correlated with the affinity for the serotonin 2A receptor, but not for the dopamine D2 receptor of each drug (including atypical antipsychotics). In contrast, the ED50 value of the drugs to reverse the apomorphine-induced PPI disruption was significantly correlated with the affinity for the dopamine D2 receptor (including typical antipsychotics). Thus the drug that antagonizes the disruption of PPI caused by PCP or DA agonists would be a candidate for a therapeutic agent for the sensorimotor gating deficit state in schizophrenic patients. Neural mechanisms underlying the disruption of PPI were reviewed.

[The characteristics of the hypothalamic monoaminergic regulation of adrenal cortical function in patients with hyperandrogenemia]. / Osobennosti gipotalamicheskoi monoaminergicheskoi reguliatsii funktsii kory nadpochechnikov u bol'nykh s giperandrogenemiei.

Since the majority of monoamines cannot penetrate through the hematoencephalic barrier, it is difficult to study their central metabolic disturbances. The ethymisole test was used to study the adrenocortical function in patients with hyperandrogenemia; ethymisole can penetrate through this barrier, it stimulates the brain structures that regulate adrenocortical function via endogenic monoamines activation. In 10 patients with the common form of ovarian polycystosis the ACTH and hydrocortisone response to ethymisole administration was virtually the same as in the reference group. This response was enhanced in 13 patients with ovarian polycystosis and adrenal hyperandrogenemia, and it could be arrested by ciproheptadin. This fact evidences, that the adrenal component of hyperandrogenemia is explained by hyperactivity of the hypothalamic serotoninergic systems, that regulate the secretion of corticotropin releasing factor. In 8 patients with ovarian polycystosis and functional hyperprolactinemia ACTH and hydrocortisone reaction to ethymisole administration was reduced; such type of response is observed in metoclopramide blocking of dopaminergic receptors. This fact points to the presence of hypothalamic dopaminergic insufficiency in the patients with ovarian polycystosis and hyperprolactinemia, this insufficiency involving not only the adrenocortical function regulating centers, but, possibly, the tuberoinfundibular system structures as well.