The interplay between ventro striatal BDNF levels and the effects of valproic acid on the acquisition of ethanol-induced conditioned place preference in mice.

Alcohol addiction is a chronic, relapsing and progressive brain disease with serious consequences for health. Compulsive use of alcohol is associated with the capacity to change brain structures involved with the reward pathway, such as ventral striatum. Recent evidence suggests a role of chromatin remodeling in the pathophysiology of alcohol dependence and addictive-like behaviors. In addition, neuroadaptive changes mediated by the brain-derived neurotrophic factor (BDNF) seems to be an interesting pharmacological target for alcoholism treatment. In the present study, we evaluated the effects of the deacetylase inhibitor valproic acid (VPA) (300mg/kg) on the conditioned rewarding effects of ethanol using conditioned place preference (CPP) (15% v/v; 2g/kg). Ethanol rewarding effect was investigated using a biased protocol of CPP. BDNF levels were measured in the ventral striatum. Ethanol administration induced CPP. VPA pretreatment did not reduce ethanol-CPP acquisition. VPA pretreatment increased BDNF levels when compared to ethanol induced-CPP. VPA pretreatment increased BDNF levels even in saline conditioned mice. Taken together, our results indicate a modulatory effect of VPA on the BDNF levels in the ventral striatum. Overall, this study brings initial insights into the involvement of neurotrophic mechanisms in the ventral striatum in ethanol-induced addictive-like behavior.

Electroencephalographic study of chlorpromazine alone or combined with alpha-lipoic acid in a model of schizophrenia induced by ketamine in rats.

Schizophrenia is characterized by behavioral symptoms, brain function impairments and electroencephalographic (EEG) changes. Dysregulation of immune responses and oxidative imbalance underpins this mental disorder. The present study aimed to investigate the effects of the typical antipsychotic chlorpromazine (CP) alone or combined with the natural antioxidant alpha-lipoic acid (ALA) on changes in the hippocampal average spectral power induced by ketamine (KET). Three days after stereotactic implantation of electrodes, male Wistar rats were divided into groups treated for 10 days with saline (control) or KET (10 mg/kg, IP). CP (1 or 5 mg/kg, IP) alone or combined with ALA (100 mg/kg, P.O.) was administered 30 min before KET or saline. Hippocampal EEG recordings were taken on the 1st, 5th and 10th days of treatment immediately after the last drug administration. KET significantly increased average spectral power of delta and gamma-high bands on the 5th and 10th days of treatment when compared to control. Gamma low-band significantly increased on the 1st, 5th and 10th days when compared to control group. This effect of KET was prevented by CP alone or combined with ALA. Indeed, the combination of ALA 100 + CP1 potentiated the inhibitory effects of CP1 on gamma low-band oscillations. In conclusion, our results showed that KET presents excitatory and time-dependent effects on hippocampal EEG bands activity. KET excitatory effects on EEG were prevented by CP alone and in some situations potentiated by its combination with ALA.

Involvement of monoaminergic systems in anxiolytic and antidepressive activities of the standardized extract of Cocos nucifera L.

Extracts from the husk fiber of Cocos nucifera are used in folk medicine, but their actions on the central nervous system have not been studied. Here, the anxiolytic and antidepressant effects of the standardized hydroalcoholic extract of C. nucifera husk fiber (HECN) were evaluated. Male Swiss mice were treated with HECN (50, 100, or 200 mg/kg) 60 min before experiments involving the plus maze test, hole-board test, tail suspension test, and forced swimming test (FST). HECN was administered orally (p.o.) in acute and repeated-dose treatments. The forced swimming test was performed with dopaminergic and noradrenergic antagonists, as well as a serotonin release inhibitor. Administration of HECN in the FST after intraperitoneal (i.p.) pretreatment of mice with sulpiride (50 mg/kg), prazosin (1 mg/kg), or p-chlorophenylalanine (PCPA, 100 mg/kg) caused the actions of these three agents to be reversed. However, this effect was not observed after pretreating the animals with SCH23390 (15 µg/kg, i.p.) or yohimbine (1 mg/kg, i.p.) The dose chosen for HECN was 100 mg/kg, p.o., which increased the number of entries as well as the permanence in the open arms of the maze after acute and repeated doses. In both the forced swimming and the tail suspension tests, the same dose decreased the time spent immobile but did not disturb locomotor activity in an open-field test. The anxiolytic effect of HECN appears to be related to the GABAergic system, while its antidepressant effect depends upon its interaction with the serotoninergic, noradrenergic (α1 receptors), and dopaminergic (D2 dopamine receptors) systems.

Antidepressant, antioxidant and neurotrophic properties of the standardized extract of Cocos nucifera husk fiber in mice.

The plant Cocos nucifera and its derivatives have shown antidepressant-like effects, although its hydroalcoholic extract has not been studied with this end in mind. Therefore, we decided to determine the antidepressant-like effects of the standardized hydroalcoholic extract of Cocos nucifera husk fiber (HECN) as well as oxidative alterations in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST), and the levels of brain-derived neurotrophic factor (BDNF) in the HC of mice. The extract was characterized based on the content of total polyphenols as well as two phenol compounds-catechin and chlorogenic acid-by HPLC-PDA. Male animals were treated per os (p.o.) for 7 days with distilled water or HECN (50, 100 or 200 mg/kg), or intraperitoneally with vitamin E (Vit E 400 mg/kg). One hour after the last drug administration, the animals were submitted to the open field test, forced swimming test (FST), tail suspension test (TST) and, immediately after the behavioral tests, had their brain removed for neurochemical determinations. The results showed that HECN100 decreased the immobility time in the FST and TST presenting, thus demonstrating an antidepressant-like effect. The administration of HECN decreased malondialdehyde levels in all doses and brain areas studied with the exception of HECN50 in the HC. The administration of HECN also decreased nitrite levels in all doses and brain regions studied. HECN100 also increased the levels of BDNF in HC of mice. In conclusion, we demonstrated that HECN has antidepressant-like properties, probably based on its antioxidant and neurotrophic effects, and is thus relevant for the treatment of depression.