Effect of Imipramine, Paroxetine, and Lithium Carbonate on Neurobehavioral Changes of Streptozotocin in Rats: Impact on Glycogen Synthase Kinase-3 and Blood Glucose Level

Abstract

Recent studies have demonstrated a scrutinized association of diabetes mellitus with depressive symptoms and major depression. Glycogen synthase kinase-3 (GSK-3) is a protein kinase enzyme constitutively active in non-stimulated cells and in multiple signalings. Independent lines of research provide a converging evidence for an involvement of GSK-3 in the regulation of behavior and hyperglycemia. The present study revealed that streptozotocin (STZ)-induced diabetic rats were found to show lengthened duration of immobility in the forced-swimming test (FST) and reduced locomotor and exploratory activities in the open-field test (OFT). Imipramine (15 mg/kg), Paroxetine (10 mg/kg) and lithium carbonate (36.94 mg/kg) for 14 days reduced immobility behavior in FST. Paroxetine and lithium carbonate increased the locomotor and exploratory activities, while imipramine decreased the locomotor activity in the OFT. Imipramine and lithium carbonate reduced the blood glucose level while paroxetine didn't alter it. STZ-induced diabetes increased GSK-3 gene expression which was determined using the reverse transcription-quantitative polymerase chain reaction test, while the three drugs decreased its expression. It can be concluded that lithium carbonate and imipramine can control both hyperglycemia and the associated symptoms of depression at the same time by inhibiting GSK-3 activity. On the other hand, paroxetine may only manage the depressive-like symptoms associated with diabetes through modulating the enzyme GSK-3, without changing blood glucose levels.

Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation

“…In addition, it was suggested that beneficial effect on sleep patterns might be synergistic to other mechanisms elicited by quetiapine toward the antidepressant therapeutic, when added to classical antidepressants or as monotherapy [61]. Other studies have found that imipramine, a classic antidepressant, reduced immobility in the forced swimming test in diabetic rats, while also reduced locomotor activity in the open field [7,40]. Still, regarding the effects of locomotor activity, some studies suggest that reduction of motor activity in the open field is correlated with increased immobility, whereas other authors have shown that locomotor activity is not underlying the performance of animals in the forced swim test [11].…”

<p>Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment</p>

“…Each rat received 10 mg/kg/day DH. 35 The first group received DH solution by oral gavage, the second group received the optimized DH-TENV gel, and the third group received the control DH gel. Gel (1 g) was spread over 4 cm 2 of the dorsal surface of the relevant rats after shaving.…”

Molecular Signatures of Lithium Treatment: Current Knowledge

“…In rodents, chronic Li treatment modulates the mRNA levels of several genes in the brain [40,41]. Li also decreases GSK3b activity, and enzyme level in the rat hippocampus [42]. Similarly, the observed increases in rat hippocampal vesicle associated membrane protein 2, syntaxin1a, synaptophysin, synaptosome-associated protein 25, synuclein, and cysteine string protein alpha after Li treatment, as well as the increase of synapsin 1 in the rat prefrontal cortex, are consistent with a Li effect on neurotransmitter re- [43,44].…”