Effects of chronic administration of adipokinetic and hypertrehalosemic hormone on animal behavior, BDNF, and CREB expression in the hippocampus and neurogenesis in mice

Abstract

Neurosecretory cells in corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosaemic or hyperprolinaemic, depending on insect in question. This study investigated effects of chronic administration of Anax imperator adipokinetic hormone (Ani-AKH), Libellula auripennis adipokinetic hormone (Lia-AKH), and Phormia-Terra hypertrehalosaemic hormone (Pht-HrTH) on depression, anxiety, analgesy, locomotion in forced swimming (FST), elevated plus-maze (EPM), hot plate, and locomotor activity tests. Ani-AKH (1 and 2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH (1 and 2 mg/kg) had antidepressant effects in forced swimming test. Lia-AKH (2 mg/kg) and Pht-HrTH (1 and 2 mg/kg) had anxiolytic effects when given chronically in elevated plus-maze test. Ani-AKH (1 and 2 mg/kg) and Pht-HrTH (2 mg/kg) had antinociceptive effects in hot plate test in male balb-c mice. Ani-AKH (2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH had locomotion-enhancing effects in locomotor activity test in male balb-c mice. Drug treatment significantly increased brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) gene expression levels compared to control levels. Pht-HrTH and Ani-AKH groups had significantly increased numbers of BrdU-labeled cells, while neurodegeneration was lower in the Pht-HrTH group. Our study showed that AKH/RPCH family peptides may be used in treatment of psychiatric illness such as depression and anxiety, in treatment of pain and in diseases related to locomotion system. AKH/RPCH family peptides increase neurotrophic factors in brain and have potential proliferative and neuroprotective effects in hippocampal neurogenesis and neurodegeneration.

Effects of the adipokinetic hormone/red pigment‐concentrating hormone (AKH/RPCH) family of peptides on MK‐801‐induced schizophrenia models

“…For example, in the AAPA test, Ani‐AKH reversed hyperlocomotion caused by MK‐801 while Lia‐AKH had a partial effect, while Pht‐HrTH increased the total distance moved when combined with MK‐801. In our recent studies, we found that when these hormones were administered chronically, they all increased locomotion , while Ani‐AKH diminished locomotion at the 4‐mg/kg dose when administered acutely . In the AAPA test, we administered the drugs subchronically and Ani‐AKH decreased MK‐801‐induced hyperlocomotion, a finding that corresponded with our previous study findings .…”

“…The intranasal administration of oxytocin has been proposed as a possible route of delivery to the central nervous system for oxytocin . AKH has a similar structure to that of oxytocin, and its central effects seem to be comparable to oxytocin in this study and in previous studies . However, oxytocin has more distinct effects than AKH in schizophrenia models in recent studies .…”

“…Additionally, in the AAPA test, some nonspecific factors, such as anxiety, can affect the results. In our recent study, we showed antidepressant and anxiolytic effects of AKH both after acute and chronic administration . NMDA antagonists such as MK‐801 are also known to possess anxiolytic effects .…”

“…We found that all the hormones reversed MK‐801‐induced cognition deficits in the AAPA test, although AKH did not reverse MK‐801‐induced PPI disruption, although Lia‐AKH significantly increased the impaired effect of MK‐801. In our previous study , we showed that the chronic administration of AKH increased brain‐derived neurotrophic factor (BDNF) and c‐AMP response element‐binding protein (CREB) levels in the hippocampus of naive mice after 2 weeks of intraperitoneal administration. It was shown that, in depression and schizophrenia, the BDNF and CREB levels were decreased in the hippocampus of patients while antidepressant and antipsychotic therapy increased the diminished levels of BDNF and CREB levels, which is thought to be responsible for the procognitive and mood enhancement effect of these drugs .…”

“…Immunoreactive cells were present in the dorsal gray commissure of the lumbosacral spinal cord, hypothalamic periventricular nucleus, and cerebral cortex . In our recent study, we showed that the (AKH/RPCH) peptide family possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects after chronic injection in mice .…”