Metabolic and behavioral effects of chronic olanzapine treatment and cafeteria diet in rats.

Olanzapine and highly palatable diets can alter metabolism and brain function. We investigated the interaction of chronic treatment (4 months) with olanzapine and a cafeteria diet on metabolic parameters, memory tasks (spatial and aversive), the elevated plus maze and locomotor activity induced by d-amphetamine. Male Wistar rats were separated into the following groups: standard diet vehicle, standard diet and olanzapine, cafeteria diet vehicle and cafeteria diet and olanzapine. Olanzapine was administered in the drinking water (approximately 1.5 mg/kg/day), and after 3 days of treatment, the rats exhibited an expected anxiolytic effect and reduced amphetamine-induced hyperlocomotion. After 4 months of treatment, cafeteria diet vehicle and cafeteria diet olanzapine rats exhibited an increased body weight and heavier fat pads compared with the standard diet groups. Olanzapine increased only the epididymal and mesenteric fat pads. The cafeteria diet and olanzapine group showed greater glucose intolerance compared with all other groups. The cafeteria diet altered the effects of chronic olanzapine on the performance in the water maze and inhibitory avoidance tasks. Chronic olanzapine treatment failed to affect amphetamine-induced locomotion and to produce anxiolytic effects in the elevated plus maze task, regardless of the diet. Our results suggest that chronic olanzapine caused an increase in fat pads, which is putatively involved in the etiology of many metabolic diseases. Rats on the cafeteria diet were overweight and exhibited glucose intolerance. We did not observe these effects with olanzapine treatment with the standard diet. Moreover, the chronic treatment regimen caused tolerance to the antipsychotic and anxiolytic effects of olanzapine and seemed to potentiate some of the metabolic effects of the cafeteria diet. The cafeteria diet also modified the effects of chronic treatment with olanzapine on cognitive tasks, which may represent an undesirable effect of poor diets in psychiatric patients.

Increased S100B serum levels in dilated cardiomyopathy patients.

BACKGROUND: The S100B protein is considered a biochemical marker for brain injuries. However, our group demonstrated that the isolated rat heart releases S100B. In this study, we investigated the serum levels of S100B in dilated cardiomyopathy (DCM) patients to evaluate its levels in heart disease. METHODS AND RESULTS: We selected DCM patients, excluding any condition that could influence S100B serum levels. Control individuals were sex and age matched. Both groups were submitted to clinical evaluation and echocardiography. We measured the S100B and NT-proBNP serum levels (expressed as median [interquartile range]). NT-proBNP levels in patients group (1462 pg/mL [426-3591]) were higher than in controls (35 pg/mL [29-55]), P < .001. S100B serum levels were higher in patients group (0.051 microg/L [0.022-0.144]) than in controls (0.017 microg/L [0.003-0.036]), P = .009. Additionally, we found a positive correlation between S100B and NT-proBNP serum levels only in patients group (Spearman's coefficient r = 0.534; P = .013). CONCLUSIONS: Although we cannot rule out the influence of S100B from brain, the positive correlation between S100B and NT-proBNP levels in DCM patients points to the myocardium as the main source for the rise in S100B serum levels.

Blockade of adenosine A1 receptors in the posterior cingulate cortex facilitates memory in rats.

Male Wistar rats were bilaterally implanted with indwelling cannulae in the caudal region of the posterior cingulate cortex. After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock) and received, immediately after training, a 0.5-microl infusion of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA; 1, 50 or 100 nM) or of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1, 25 or 50 nM). Animals were tested twice, 1.5 h and, again, 24 h after training, in order to examine the effects of these agents on short- and long-term memory, respectively. Only 50-nM DPCPX was effective in altering memory, promoting a facilitation. These results suggest that adenosine A1 receptors in the posterior cingulate cortex inhibit memory consolidation in a way that their blockade facilitates memory for inhibitory avoidance in rats.

Effects of chronic administered guanosine on behavioral parameters and brain glutamate uptake in rats.

Oral and intraperitoneal administration of the nucleoside guanosine have been shown to prevent quinolinic acid- (QA) and alpha-dendrotoxin-induced seizures, impair memory, and impair anxiety in rats and mice. We investigated the effect of 2-weeks ad lib orally administered guanosine (0.5 mg/ml) on seizures induced by QA, inhibitory avoidance memory, and locomotor performance in rats. We also studied the mechanism of action of guanosine through the measurement of its concentration in the cerebrospinal fluid (CSF) and its effect on glutamate uptake in cortical slices of rats. QA produced seizures in 85% of rats, an effect partially prevented by guanosine (53% of seizures; P = 0.0208). Guanosine also impaired retention on the inhibitory avoidance task (P = 0.0278) and decreased locomotor activity on the open field test (P = 0.0101). The CSF guanosine concentration increased twofold in the treated group compared to that in the vehicle group (P = 0.0178). Additionally, QA promoted a 30% decrease in glutamate uptake as compared to that with intracerebroventricular saline administration, an effect prevented by guanosine in animals protected against QA-induced seizures. Altogether, these findings suggest a potential role of guanosine for treating diseases involving glutamatergic excitotoxicity such as epilepsy. These effects seem to be related to modulation of glutamate uptake.