Apical periodontitis induces changes on oxidative stress parameters and increases Na+/K+-ATPase activity in adult rats.

OBJECTIVES: Endodontic infection can cause systemic alterations. The involvement of oxidative stress (OS) and transmembrane enzymes compose the pathogenesis of various systemic diseases. However, the relation among apical periodontitis (AP), OS parameters, and Na+/K+-ATPase (NKA) pump was not reported in the literature. This study evaluated the AP influence on OS parameters and NKA activity in adult rats. METHODS: Adult male Wistar rats (sixteen weeks old) were randomly assigned to two experimental groups: control (CT group; n = 8) and AP (AP group; n = 9), which was induced in the first right mandibular molar tooth. After 21 days of AP induction, mandibles were dissected for radiographic analysis. In addition, the heart, liver, pancreas, and kidney were collected for analysis of endogenous OS parameters and NKA activity. Data were analyzed by Student's T-test. Values of p < 0.05 were considered statistically significant. RESULTS: AP presence increased reactive species (RS) generation only in the heart, while the other analyzed organs did not have this parameter modified. Heart and pancreas had a decreased endogenous antioxidant system (catalase activity and vitamin C levels), liver and kidney had an increased one. AP increased NKA activity in the heart, liver, and pancreas, but not in the kidney. CONCLUSION: The modulation of both endogenous antioxidant defense system and NKA activity in vital organs suggested that alterations in the antioxidant status and cellular electrochemical gradient may be involved in the AP pathophysiology.

Modafinil reduces amphetamine preference and prevents anxiety-like symptoms during drug withdrawal in young rats: Involvement of dopaminergic targets in VTA and striatum.

Drug abuse and addiction are overwhelming health problems mainly during adolescence. Based on a previous study of our research group, the rats that received modafinil (MD) during the adolescence showed less preference for amphetamine (AMPH) in adulthood. Our current hypothesis is that MD will show beneficial effects against AMPH preference and abstinence symptoms during adolescence, a critical lifetime period when drug hedonic effects are more pronounced. We investigated the influence of MD pretreatment on AMPH preference in conditioned place preference (CPP) paradigm in adolescent rats and anxiety-like symptoms during drug withdrawal (48 h after the last AMPH dose) in elevated plus maze (EPM) task. Besides that, oxidative and molecular status were evaluated in the ventral tegmental area (VTA) and striatum. Our findings showed, as it was expected, that adolescent animals developed AMPH preference together with anxiety-like symptoms during the drug withdrawal while the MD pretreatment prevented those behaviors. Besides promoting benefits on reward parameters, MD was able to preserve VTA and striatum from oxidative damages. This was observed by the increased catalase activity and reduced generation of reactive species and lipid peroxidation, which were inversely modified by AMPH exposure. At molecular level, MD exerted an interesting modulatory activity on the VTA and induced an up-regulation in striatal dopaminergic targets (TH, DAT, D1R and D2R). So far, during the adolescence, MD presented beneficial behavioral outcomes that could be attributed to its modulatory activity on the striatal dopaminergic system in an attempt to maintain the adequate dopamine levels.

Could Modafinil Prevent Psychostimulant Addiction? An Experimental Study in Rats.

Addiction is a serious health problem which leads to general social impairment. The period of adolescence plays a significant role in drug abuse liability. Psychostimulants, such as modafinil (MOD), are majorly used by teenagers seeking improvements in cognition, which contributes to its indiscriminate use. This study aimed to investigate the influence of MOD (64 mg/kg by gavage, once a day) treatment during adolescence [post-natal day (PND) 28-42] on amphetamine (AMPH, 4 mg/kg i.p.)-conditioned place preference (CPP) in early adulthood (PND 60). Our findings showed that AMPH increased CPP for the drug and anxiety-like behaviours; on the other hand, AMPH decreased the number of crossings and recognition index. In addition, AMPH decreased catalase activity and increased reactive species, malondialdehyde and carbonyl protein levels in the hippocampus. AMPH also increased pro-brain derived neurotrophic factor (BDNF), tyrosine kinase receptor B, dopamine transporter, D1R and decreased BDNF and D2R immunoreactivity. Contrarily, animals pre-exposed to MOD showed reduced AMPH-CPP, no locomotor impairment, less anxiety-like behaviours and no memory deficits. In addition, MOD showed antioxidant activity by preventing AMPH-induced oxidative damage in the hippocampus. Moreover, molecular analysis showed that MOD was able to modulate the hippocampal dopaminergic system, thus preventing AMPH-induced impairments. Animals that received MOD during adolescence showed reduced AMPH-CPP in early adulthood. These unexpected behavioural effects of MOD on CPP could be due to its hippocampal dopaminergic system modulation, mainly by its action on D1R, which is closely linked to drug addiction. Nevertheless, further studies are necessary.

Stress during the gestational period modifies pups' emotionality parameters and favors preference for morphine in adolescent rats.

Experimental animal studies have shown that early life periods are highly vulnerable to environmental factors, which may exert prolonged impact on HPA axis function and on subsequent neurochemical and behavioral responses in adulthood. Here we evaluated the influence of environmental stressful situations in two different early life stages on stress-related behaviors, and morphine-conditioned place preference (CPP), which is indicative of addiction. While in the gestational stress (Gest-S) dams were exposed to daily sessions of chronic mild stress (CMS) for 2 weeks, in the postnatal stress (post-NS) the offspring were exposed daily to neonatal isolation from postnatal day (PND) 2 to PND 9 for 60 min. Animals exposed to post-NS showed lesser anxiety in different behavioral paradigms (elevated plus maze-EPM and defensive burying test-DBT) as well as increased exploratory behavior (open-field task-OFT), and no preference for morphine in CPP. In contrast, animals exposed to Gest-S showed increased corticosterone plasma levels together with anxiety symptoms and greater preference for morphine following three days of drug withdrawal. Our findings indicate that the gestational period is critical for stress, whose effects may be manifest throughout life. On the other hand, post-NS can trigger neuroadaptations able to overcome emotional consequences of early life. We hypothesized that Gest-S is able to modify responses to opioids along adulthood, which may facilitate development of addiction to these drugs.