Ângelo L. Piato

Inhaled linalool-induced sedation in mice.

Linalool is a monoterpene often found as a major component of essential oils obtained from aromatic plant species, many of which are used in traditional medical systems as hypno-sedatives. Psychopharmacological evaluations of linalool (i.p. and i.c.v.) revealed marked sedative and anticonvulsant central effects in various mouse models. Considering this profile and alleged effects of inhaled lavender essential oil, the purpose of this study was to examine the sedative effects of inhaled linalool in mice. Mice were placed in an inhalation chamber during 60 min, in an atmosphere saturated with 1% or 3% linalool. Immediately after inhalation, animals were evaluated regarding locomotion, barbiturate-induced sleeping time, body temperature and motor coordination (rota-rod test). The 1% and 3% linalool increased (p<0.01) pentobarbital sleeping time and reduced (p<0.01) body temperature. The 3% linalool decreased (p<0.01) locomotion. Motor coordination was not affected. Hence, linalool inhaled for 1h seems to induce sedation without significant impairment in motor abilities, a side effect shared by most psycholeptic drugs.

Antidepressant-like effects of melatonin in the mouse chronic mild stress model.

Melatonin is a hormone primarily synthesized by the pineal gland and has been shown to govern seasonal and circadian rhythms, as well as the immune system, certain behaviours, and responses to stress. Chronic exposure to stress is involved in the etiology of human depression, and depressed patients present changes in circadian and seasonal rhythms. This study investigated the effects of daily exogenous melatonin (1 and 10 mg/kg, p.o.) and imipramine (20 mg/kg, i.p.) on the changes in the coat state, grooming behaviour and corticosterone levels induced by the unpredictable chronic mild stress model of depression in mice. As expected, the 5 weeks of unpredictable chronic mild stress schedule induced significant degradation of the coat state, decreased grooming and increased serum corticosterone levels. All of these unpredictable chronic mild stress-induced changes were counteracted by melatonin (P<0.05) and imipramine (P<0.01). Especially in view of the relevance of stress as a major contributing factor in depression, as well as the alleged importance of normalizing a hyperfunctioning HPA axis and resynchronizing circadian rhythms for a successful treatment of depression, this study reassesses the potential of melatonin as an antidepressant.

Antidepressant profile of Ptychopetalum olacoides Bentham (Marapuama) in mice.

Depression has become of universal major importance, and it is therefore vital to expand the armamentarium for treating the condition. Lack of motivation and lassitude are major symptoms treated with the use of Marapuama (Ptychopetalum olacoides, PO) remedies by communities in the Brazilian Amazon. Considering the prominence of such symptoms in depression, the present study was designed to verify the effects of a standardized PO ethanol extract (POEE) on the forced swimming (FST) and tail suspension tests (TST). POEE i.p. (15–100 mg/kg) and oral (300 mg/kg) resulted in a significant and dose‐related anti‐immobility effect. We further examined the involvement of dopamine, noradrenaline and serotonin in these antidepressant‐like effects. POEE effects were prevented when catecholamine synthesis was inhibited by ‐α‐methyl‐ρ‐tyrosine (AMPT) (100 mg/kg, i.p.), while inhibition of serotonin synthesis with ρ‐chlorophenylalanine methyl ester hydrochloride (PCPA) (100 mg/kg, i.p.) was devoid of effect. The blockade of β‐adrenergic (propranolol 2 mg/kg, i.p.) and D1 dopamine (SCH 23390 0.5 mg/kg, i.p.) receptors prevented POEE anti‐immobility effects; by contrast, blockade of D2 dopamine (sulpiride 2 and 50 mg/kg, i.p.) receptors was ineffective. Consistent with traditional use, the results indicate that POEE possesses antidepressant‐like effects, possibly mediated by β‐adrenergic and D1 dopamine receptors. Copyright

Alstonine as an Antipsychotic: Effects on Brain Amines and Metabolic Changes

Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications.

6-Sulfatoxymelatonin as a predictor of clinical outcome in depressive patients

This study established the value of the 6‐sulfatoxymelatonin (aMT6s) urine concentration as a predictor of the therapeutic response to noradrenaline reuptake inhibitors in depressive patients.