Experimentally exposed toxic effects of long-term exposure to environmentally relevant concentrations of CIP in males and females of the silver catfish Rhamdia quelen.

Ciprofloxacin (CIP) is an antibiotic commonly used in human and veterinary medicine. It is present in the aquatic environment, but we still know very little about its effect on non-targeted organisms. This study aimed to evaluate the effects of long-term exposure to environmental CIP concentrations (1, 10, and 100 µg.L-1) in males and females of Rhamdia quelen. After 28 days of exposure, we collected the blood for the analysis of hematological and genotoxic biomarkers. Additionally, we measured 17 ß-estradiol and 11 keto-testosterone levels. After the euthanasia, we collected the brain and the hypothalamus to analyze acetylcholinesterase (AChE) activity and neurotransmitters, respectively. The liver and gonads were assessed for biochemical, genotoxic, and histopathological biomarkers. At 100 µg.L-1 CIP, we observed genotoxicity in the blood, nuclear morphological changes, apoptosis, leukopenia, and a reduction of AChE in the brain. In the liver was observed oxidative stress and apoptosis. At 10 µg.L-1 CIP, leukopenia, morphological changes, and apoptosis were presented in the blood and a reduction of AChE in the brain. Apoptosis, leukocyte infiltration, steatosis, and necrosis occurred in the liver. Even at the lowest concentration (1 µg.L-1), adverse effects such as erythrocyte and liver genotoxicity, hepatocyte apoptosis, oxidative stress, and a decrease in somatic indexes were observed. The results showed the importance of monitoring CIP concentrations in the aquatic environment that cause sublethal effects on fish.

Two-weeks treatment with cannabidiol improves biophysical and behavioral deficits associated with experimental type-1 diabetes.

The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality. Cannabidiol (CBD) has been identified as a therapeutic agent viable to treat diverse psychiatric disorders. Thus, this study aimed to investigate the effect of CBD treatment (once a day for 14 days starting two weeks after diabetes induction; at doses of 0, 3, 10 or 30 mg/kg, i.p.) on depression- and anxiety-like behaviors associated with experimental diabetes induced by streptozotocin (60 mg/kg; i.p.) in rats. Levels of plasma insulin, blood glucose, and weight gain were evaluated in all experimental groups, including a positive control group treated with imipramine. The rats were tested in the modified forced swimming test (mFST) and elevated plus maze (EPM) test. Besides, the levels of serotonin (5-HT), noradrenaline (NA) and dopamine (DA) in two emotion-related brain regions, the prefrontal cortex (PFC) and hippocampus (HIP) were evaluated using high-pressure liquid chromatography. Our results showed that CBD treatment (only at the higher dose of 30 mg/kg) reduced the exaggerated depressive- and anxiogenic-like behaviors of diabetic (DBT) rats, which may be associated with altered 5-HT, NA and/or DA levels observed in the PFC and HIP. Treatment with CBD (higher dose) also induced a significant increase in weight gain and the insulin levels (and consequently reduced glycemia) in DBT rats. The long-term CBD effects gave rise to novel therapeutic strategies to limit the physiological and neurobehavioral deficits in DBT rats. This approach provided evidence that CBD can be useful for treating psychiatry comorbidities in diabetic patients.

Diazepam blocks 50 kHz ultrasonic vocalizations and stereotypies but not the increase in locomotor activity induced in rats by amphetamine.

RATIONALE: We have recently shown that the benzodiazepine diazepam inhibits dopamine release in the NAc and blocks the increased release of dopamine induced by DL-amphetamine. Rewarding stimuli and many drugs of abuse can induce dopamine release in the nucleus accumbens as well as 50-kHz ultrasonic vocalizations (USVs) in rats. OBJECTIVES: In the present study, we tested the hypothesis that diazepam can also block the increase in locomotor activity and USVs elicited by amphetamine. METHODS: Fifty-kilohertz USVs, stereotypy, and locomotor behavior were scored in adult male Wistar rats treated with i.p. injections of saline, 3 mg/kg DL-amphetamine, 2 mg/kg diazepam, 0.2 mg/kg haloperidol, or a combination of these drugs. RESULTS: In agreement with previous studies, amphetamine caused significant increases in the number of USV calls, stereotypies, and locomotor activity. The D2 dopamine receptor antagonist haloperidol blocked the effects of amphetamine on USVs, stereotypy, and locomotor activity. Diazepam blocked the effect of amphetamine on USV and stereotypy, but not on horizontal locomotion. CONCLUSIONS: These results suggest that diazepam blocks the rewarding effect of amphetamine. This finding is promising for basic research regarding treatments of substance use disorders and evaluation of the impact of benzodiazepines on motivation.