Qualea grandiflora Mart. (“pau-terra”) is a medicinal plant symbolic from Cerrado biome. Qualea species reportedly have antiparasitic properties, but their active compounds have yet to be identified. In this study, we investigated the antiplasmodial activity of Q. grandiflora fruit and stem extracts against Plasmodium falciparum. The polar extracts of both fruits and stems showed promising in vitro antiplasmodial activity against sensitive and resistant P. falciparum strains (half-maximal inhibitory concentration (IC50) = 1.2 and 4.2 ng mL-1, respectively), low cytotoxicity against human hepatic cells (IC50HepG2 ≥ 400 ng mL-1), and a noteworthy selectivity index (SI ≥ 322 and ≥ 96, respectively). The fruit ethanolic extract revealed significant oral efficacy at 100 mg kg-1 in a mouse model of P. berghei malaria (100% reduction in parasitemia on day 5 post-infection). To investigate the chemical composition of the extracts, we developed a method involving liquid chromatography-high resolution quadrupole-time of flight mass spectrometer. The chemical profiling of active extracts indicated 32 compounds, including gallotannins, ellagic acid derivatives and flavonoids. The common component in the active polar extracts was found to be ellagic acid (EA), which may contribute favorably to the in vitro and in vivo inhibitory activity observed in this study.

Studies in humans suggest that exposure to stress is related to relapse to tobacco use. The reinstatement of conditioned place preference (CPP) provides a simple, noninvasive and easy approach to investigate the mechanisms for drug relapse. The present study investigated whether repeated exposure to stress could change the extinction and reinstatement of nicotine-induced CPP. Adult male Wistar were exposed to restraint-stress for 2 hours/daily for 7 days, while the control-group was left undisturbed during this period. One day after the last stress session the CPP protocol was carried out. Nicotine produced a place preference to the compartment paired with its injections during conditioning (.16 mg/kg, s.c.; four drug sessions). Once established, nicotine place preference was extinguished by alternate exposure to each compartment after a saline injection (four exposures to each compartment). The animals that did not show extinction of CPP were submitted to two other extinction sessions. Following this extinction phase, the reinstatement of place conditioning was investigated following a priming injection of nicotine. Both control and stress groups showed reinstatement of CPP. The percentage of rats from the stress group that extinguished nicotine-CPP in the first and second test was lower as compared to the control group. In conclusion, stress delayed the extinction of the nicotine-induced CPP, but did not modify the reinstatement.

A maioria dos estudos pré-clínicos e clínicos aponta a nicotina como o principal agente responsável pelo desenvolvimento da dependência ao tabaco. Muitos trabalhos têm demonstrado que as bases neurais da dependência à nicotina são semelhantes àquelas das outras drogas de abuso. A nicotina induz preferência condicionada por lugar e auto-administração e, portanto, atua como reforçador positivo, esse efeito parece ser mediado pelo sistema dopaminérgico mesolímbico. A nicotina também induz à sensibilização comportamental que é provavelmente resultante de alterações da expressão gênica do núcleo acumbens induzidas pela exposição prolongada a essa substância. A suspensão do uso de nicotina resulta em síndrome de abstinência. As evidências indicam que esses sinais e sintomas sejam mediados por receptores colinérgicos nicotínicos centrais e periféricos. Outros neurotransmissores, como por exemplo a serotonina e os peptídeos opióides, também podem estar envolvidos na mediação da dependência e síndrome de abstinência à nicotina. A revisão da literatura mostra a complexidade dos efeitos da nicotina no organismo. A integração entre as abordagens comportamental, neuroquímica e molecular possibilitará a compreensão dos mecanismos neurais da dependência ao tabaco e fornecerá as bases para o desenvolvimento racional de agentes terapêuticos que possam ser utilizados para o tratamento da dependência e síndrome de abstinência ao tabaco.

It is generally accepted that nicotine is the major component in tobacco smoke responsible for addiction. Several studies have demonstrated that the neural mechanisms underlying nicotine addiction have much in common with those underlying the mechanisms of addiction to other drugs. Thus, it has been shown that nicotine induces conditioning place preference and self-administration across many species. Repeated treatment with nicotine also induces behavioral sensitization in rodents. These behavioral effects of nicotine seem to mediate through the meso limbic dopamine system. Smoke cessation results in an abstinence syndrome that seems to be mediated by both peripheral and central nicotinic acetylcholine receptors. In addition, other neurotransmitters systems are involved in the mediation of nicotine addiction and withdrawal. The review of the literature evidences the complexity of the behavioral, neurochemical and molecular effects of nicotine. The integration of nicotine studies across all levels will lead to a better understanding of the neurobiological mechanisms underlying the addictive actions of nicotine. The understanding of such mechanisms is crucial to the development of pharmacological agents for the treatment of tobacco addiction and withdrawal.