Chronic administration of caffeine, modafinil, AVL-3288 and CX516 induces time-dependent complex effects on cognition and mood in an animal model of sleep deprivation.

OBJECTIVE: Caffeine and modafinil are used to reverse effects of sleep deprivation. Nicotinic alpha-7 receptor and AMPA receptor positive allosteric modulators (PAM) are also potential substances in this context. Our objective is to evaluate the effects of caffeine, modafinil, AVL-3288 (nicotinic alpha-7 PAM) and CX516 (AMPA receptor PAM) on cognition and mood in a model of sleep deprivation. METHOD: Modified multiple platform model is used to sleep-deprive mice for 24 days, for 8 h/day. Vehicle, Modafinil (40 mg/kg), Caffeine (5 mg/kg), CX516 (10 mg/kg), and AVL3288 (1 mg/kg) were administered intraperitoneally daily. A cognitive test battery was applied every six days for four times. The battery that included elevated plus maze, novel object recognition, and sucrose preference tests was administered on consecutive days. RESULTS: Sleep deprivation decreased novel object recognition skill, but no significant difference was found in anxiety and depressive mood. Caffeine administration decreased anxiety-like behavior in short term, but this effect disappeared in chronic administration. Caffeine administration increased memory performance in chronic period. AVL group showed better memory performance in short term, but this effect disappeared in the rest of experiment. Although, in the modafinil group, no significant change in mood and memory was observed, anhedonia was observed in the chronic period in vehicle, caffeine and modafinil groups, but not in AVL-3288 and CX-516 groups. CONCLUSION: Caffeine has anxiolytic effect in acute administration. The improvement of memory in chronic period may be associated with the neuroprotective effects of caffeine. AVL-3288 had a short-term positive effect on memory, but tolerance to these effects developed over time. Furthermore, no anhedonia was observed in AVL-3288 and CX516 groups in contrast to vehicle, caffeine and modafinil groups. This indicates that AVL-3288 and CX516 may show protective effect against depression.

Profile of psychotropic agents used in autism spectrum disorder according to comorbidities in Turkey: A 4-year evaluation.

It is known that the use of psychotropic pharmaceuticals is common in comorbidities seen in autism spectrum disorder (ASD). We have very limited knowledge about which psychotropic drugs are prescribed when comorbidities are diagnosed in patients with ASD. It is aimed to determine the profile of psychotropic agents in patients diagnosed with ASD associated with comorbidities between the ages of 0-24 in Turkey over 4 years. Data belonging to ASD in Prescription Information System (PIS) was obtained from the 'Turkish Medicines and Medical Devices Agency'. A total of 34 066 prescriptions including 45 624 psychotropic drugs were analyzed. A total of psychotropic drugs prescribed for patients with ASD was 75.4%. The following psychotropic drugs were prescribed for the patients with ASD and its comorbidities; risperidone (28.6%), aripiprazole (13.7%), and valproic acid (11.3%) are the most preferred psychotropics. The percentage of pharmaceuticals containing psychotropic active substances in prescriptions with ASD and its comorbidities is 7.5%. This study is the first research in which psychotropics used in ASD were evaluated over a wide period and nationwide. Antipsychotics were most commonly prescribed with the diagnosis of ASD. In the presence of ASD and its comorbidities, risperidone was most frequently prescribed.