Maribel Antonello Rubin

Individuals with opioid use disorders often relapse into drug-seeking behavior after recalling memories linked to the drug use experience. Improving extinction efficacy has been used as a strategy to treat substance use disorders and suppress relapse. Although N-methyl-D-aspartate receptor (NMDAr) agonists facilitate acquisition, consolidation, and extinction, no study has addressed whether spermidine (SPD), a natural polyamine ligand of the NMDA receptor, facilitates the extinction and reinstatement of morphine-induced conditioned place preference (CPP).

Background: Central nervous system function has been emerging as an approach to understand hypertension-mediated memory dysfunction, and chronic exercise is able to modulate the purinergic system. Method: Herein, we investigated the effect of chronic swimming training on the purinergic system in cortex and hippocampus of L-NAME-induced hypertensive rats. Male Wistar rats were divided into four groups: Control, Exercise, L-NAME and Exercise L-NAME. Inhibitory avoidance test was used to assess memory status. NTPDase, CD73 and adenosine deaminase activities and expression, and P2 receptors expression were analyzed. Data were analyzed using two-way ANOVA and Kruskal–Wallis tests, considering P less than 0.05. Results: Physical exercise reduced the blood pressure and prevented memory impairment induced by L-NAME model of hypertension. L-NAME treatment promoted an increase in NTPDase1, NTPDase3 and CD73 expression and activity in the cortex. A2A expression is increased in hippocampus and cortex in the hypertension group and exercise prevented this overexpression. Conclusion: These changes suggest that hypertension increases adenosine generation, which acts through A2A receptors, and exercise prevents these effects. These data may indicate a possible mechanism by which exercise may prevent memory impairment induced by L-NAME.

Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disease. The present study investigated the effects of 50 and 100 mg/kg berberine (BRB) on recognition memory, oxidative stress, and purinergic neurotransmission, in a model of sporadic dementia of the Alzheimer’s type induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Rats were submitted to ICV-STZ 3 mg/kg or saline, and 3 days later, were started on a treatment of BRB or saline for 21 days. The results demonstrated that BRB was effective in protecting against memory impairment, increased reactive oxygen species, and the subsequent increase in protein and lipid oxidation in the cerebral cortex and hippocampus, as well as δ-aminolevulinate dehydratase inhibition in the cerebral cortex. Moreover, the decrease in total thiols, and the reduced glutathione and glutathione S-transferase activity in the cerebral cortex and hippocampus of ICV-STZ rats, was prevented by BRB treatment. Besides an antioxidant effect, BRB treatment was capable of preventing decreases in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), 5′-nucleotidase (EC-5’-Nt), and adenosine deaminase (ADA) activities in synaptosomes of the cerebral cortex and hippocampus. Thus, our data suggest that BRB exerts a neuroprotective effect on recognition memory, as well as on oxidative stress and oxidative stress-related damage, such as dysfunction of the purinergic system. This suggests that BRB may act as a promising multipotent agent for the treatment of AD.

Objective: Here we investigated the impact of chronic high-intensity interval training (HIIT) and caffeine consumption on the activities of Na⁺-K⁺-ATPase and enzymes of the antioxidant system, as well as anxiolytic-like behaviour in the rat brain. Methods: Animals were divided into groups: control, caffeine (4 mg/kg), caffeine (8 mg/kg), HIIT, HIIT plus caffeine (4 mg/kg) and HIIT plus caffeine (8 mg/kg). Rats were trained three times per week for 6 weeks, and caffeine was administered 30 minutes before training. We assessed the anxiolytic-like behaviour, Na⁺-K⁺-ATPase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) in the brain. Results and discussion: HIIT-induced anxiolytic-like behaviour increased Na⁺-K⁺-ATPase and GPx activities and TBARS levels, altered the activities of SOD and CAT in different brain regions, and decreased GSH levels. Caffeine, however, elicited anxiogenic-like behaviour and blocked HIIT effects. The combination of caffeine and HIIT prevented the increase in SOD activity in the cerebral cortex and GPx activity in three brain regions. Our results show that caffeine promoted anxiogenic behaviour and prevented HIIT-induced changes in the antioxidant system and Na⁺-K⁺-ATPase activities.