Serotonin [HRP]

Introduction: Anxiety disorders being ranked at sixth position in the global burden of diseases is affecting over 250 million people. Curcumin, an active phytochemical flavonoid, has shown to induce the monoamine neurotransmitter serotonin, a prominent neurotransmitter in modulating the brain state in anxiety. Also, evidences reveal that zinc plays a key role in human neurodevelopment and supplementation of zinc enhanced the efficacy of antidepressant drugs through synergistic action. Aim: To evaluate the synergistic antianxiety effect of curcumin and zinc on acute and chronic models of anxiety in male swiss albino mice. Materials and Methods: A total of 36 male Swiss Albino mice, weighing 20-30 g, were randomly grouped to six groups, such that each group consisted of six mice. Group 1 served as control. Group 2 received standard drug diazepam 3 mg/kg Intra Peritoneal (IP). Group 3 and 4 received curcumin at doses of 5 and 10 mg/kg, respectively. Group 5 and 6 received curcumin at doses 5 and 10 mg/kg per oral (p.o) along with zinc chloride 10 mg/kg IP, respectively. The anxiolytic effect was studied in two validated models of anxiety such as Elevated Plus Maze (EPM) test and light/dark box test. Each animal was tested initially in the EPM followed by light/dark box test after administration of drug/vehicle one hour prior to the experiment in acute study. Following a washout period of one week, the animals were utilised for the study of chronic anxiolytic effect wherein the drugs were administered once daily for 14 days. Results: Curcumin at doses of 5 mg/kg and 10 mg/kg with zinc chloride 10 mg/ kg showed a significant increase in the number of entries and time spent in open arm in EPM both on acute and chronic administration (p<0.001). In the light/dark box test, curcumin at doses of 5 mg/kg and 10 mg/kg when given along with zinc chloride 10 mg/kg significantly increased the number of entries and time spent in the light compartment both in acute and chronic models (p<0.001). Conclusion: The anxiolytic effect of synergistic action of curcumin and zinc was efficacious in both acute and chronic models of anxiety in mice.

Motor skill is a specific area of disability of Rett syndrome (RTT), a rare disorder occurring almost exclusively in girls, caused by loss-of-function mutations of the X-linked methyl-CpG-binding protein2 (MECP2) gene, encoding the MECP2 protein, a member of the methyl-CpG-binding domain nuclear proteins family. Brain 5-HT, which is defective in RTT patients and Mecp2 mutant mice, regulates motor circuits and SSRIs enhance motor skill learning and plasticity. In the present study, we used heterozygous (Het) Mecp2 female and Mecp2-null male mice to investigate whether fluoxetine, a SSRI with pleiotropic effects on neuronal circuits, rescues motor coordination deficits. Repeated administration of 10 mg/kg fluoxetine fully rescued rotarod deficit in Mecp2 He mice regardless of age, route of administration or pre-training to rotarod. The motor improvement was confirmed in the beam walking test while no effect was observed in the hanging-wire test, suggesting a preferential action of fluoxetine on motor coordination. Citalopram mimicked the effects of fluoxetine, while the inhibition of 5-HT synthesis abolished the fluoxetine-induced improvement of motor coordination. Mecp2 null mice, which responded poorly to fluoxetine in the rotarod, showed reduced 5-HT synthesis in the prefrontal cortex, hippocampus and striatum, and reduced efficacy of fluoxetine in raising extracellular 5-HT as compared to female mutants. No sex differences were observed in the ability of fluoxetine to desensitize 5-HT(1A )autoreceptors upon repeated administration. These findings indicate that fluoxetine rescues motor coordination in Mecp2 He mice through its ability to enhance brain 5-HT and suggest that drugs enhancing 5-HT neurotransmission may have beneficial effects on motor symptoms of RTT.