The aim of this study was to examine the effect of simvastatin (SMV), a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, in rats fed with a standard or a high-fat diet (HFD) throughout the prenatal and the postnatal periods. The emotional status of the animals was evaluated by elevated plus-maze and modified forced swimming tests, whereas cognitive performance was assessed by a Morris water maze task. Morphological changes in the hippocampus were examined by design-based stereology. HFD exposure significantly increased blood serum triglycerides without altering cholesterol levels relative to the controls. After four weeks of oral SMV (5 mg/kg) administration, serum triglycerides reverted to the control level. SMV caused significant anxiolytic, antidepressant-like, and nootropic effects in animals fed the standard diet. In the HFD group, enhanced anxiety and depression, and reduced cognitive performances of animals were reversed by SMV treatment. Although a total volume estimation of the hippocampal subfields indicated no significant change among the groups, the total number of pyramidal neurons decreased significantly in animals fed the HFD; following SMV treatment, this detrimental effect was reversed. In conclusion, chronic SMV administration has significant therapeutic potential for the treatment of affective and cognitive disorders with or without altering the serum lipid profiles.

Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f–3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po), indicated the antidepressant-like activities of the compounds 3c, 3d, 3f–3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.

Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR), ¹H Nuclear Magnetic Resonance Spectroscopy (¹H-NMR), ¹³C Nuclear Magnetic Resonance Spectroscopy (¹³C-NMR) and Electronspray Ionisation Mass Spectroscopy (ESI-MS) spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST) and modified forced swimming (MFST) methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg) was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME) properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives.

Context: Investigating potential central nervous system (CNS) activities of Crataegus monogyna Jacq. (Rosaceae), hawthorn, fruit extracts. Objective: Evaluating CNS effects and analgesic activities of hawthorn fruit extracts based on the traditional uses of the plant for neurosedative and pain killer actions. Materials and methods: Effects of hawthorn pulp (HPE) and seed extracts (HSE) at the dose range of 1-1000 mg/kg were examined on anxiety level, spontaneous locomotor activity, motor coordination, and nociceptive perception of mice. Morphine was used as a reference drug. Results: HPE (100-1000 mg/kg) and HSE (10-1000 mg/kg) significantly decreased not only the exploratory behaviors in hole-board experiments, but also the spontaneous locomotor activities in activity cage tests. The same doses of extracts were found to be ineffective in Rota-Rod tests of mice. In tail-clip, hot-plate, and acetic acid-induced writhing tests, quite potent and dose-dependent analgesic activities were seen at 100-1000 mg/kg doses of HPE and 10-1000 mg/kg doses of HSE. Analgesic effects observed in all analgesia tests were antagonized by naloxone. Discussion: Significant and dose-dependent decreases in spontaneous locomotor activities and exploratory behaviors of animals suggested CNS depressant activities of both extracts. Complete naloxone antagonism in all applied analgesia tests indicated opioid-related analgesic activities of both extracts. Conclusion: These findings seem to support the traditional use of this plant to treat stress, nervousness, sleep disorders, and pain control.