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

The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI). In the AAPA task, Long-Evans rats were treated with Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), Pht-HrTH (2 mg/kg), MK-801 (0.15 mg/kg), and the combination of MK-801 with the hormones subchronically. In the prepulse inhibition test, Wistar albino rats were treated with Ani-AKH (1 mg/kg), Lia-AKH (1 mg/kg), Pht-HrTH (1 mg/kg), MK-801 (0.1 mg/kg), or the combination of MK-801 with hormones acutely before the test. In our study, Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), and Pht-HrTH (2 mg/kg) reversed MK-801 (0.15 mg/kg)-induced cognitive memory impairment effects in the AAPA task. Lia-AKH (1 mg/kg) significantly potentiated the MK-801-induced PPI disruption, while Ani-AKH (1 mg/kg) partially potentiated the impairment caused by MK-801, and Pht-HrTH did not modify the effect of MK-801. In conclusion, AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK-801.

Adult neurogenesis reduction by a cytostatic treatment improves spatial reversal learning in rats.

Adult neurogenesis in the dentate gyrus adds a substantial number of new functional neurons to the hippocampus network in rodents. To date, however, the function of these new granule cells remains unclear. We conducted an experiment to assess the contribution of adult neurogenesis in the dentate gyrus to acquisition and reversal learning in a task that predominantly requires generalization of a rule. Young adult male Long-Evans rats were repeatedly administered either a cytostatic temozolomide or saline for a period of four weeks (3 injections per week). Post treatment, animals were injected with bromodeoxyuridine to quantify adult neurogenesis in the dentate gyrus. For behavioral assessment we used hippocampus-dependent active place avoidance with reversal in a Carousel maze. Animals first learned to avoid a 60° sector on the rotating arena. Afterwards, sector was relocated to the opposite side of the rotating arena (reversal). The administration of temozolomide significantly improved the reversal performance compared to saline-treated rats. Our results suggest a significant, level-dependent, improvement of reversal learning in animals with reduced adult neurogenesis in hippocampus.

Common mechanisms of pain and depression: are antidepressants also analgesics?

Neither pain, nor depression exist as independent phenomena per se, they are highly subjective inner states, formed by our brain and built on the bases of our experiences, cognition and emotions. Chronic pain is associated with changes in brain physiology and anatomy. It has been suggested that the neuronal activity underlying subjective perception of chronic pain may be divergent from the activity associated with acute pain. We will discuss the possible common pathophysiological mechanism of chronic pain and depression with respect to the default mode network of the brain, neuroplasticity and the effect of antidepressants on these two pathological conditions. The default mode network of the brain has an important role in the representation of introspective mental activities and therefore can be considered as a nodal point, common for both chronic pain and depression. Neuroplasticity which involves molecular, cellular and synaptic processes modifying connectivity between neurons and neuronal circuits can also be affected by pathological states such as chronic pain or depression. We suppose that pathogenesis of depression and chronic pain shares common negative neuroplastic changes in the central nervous system (CNS). The positive impact of antidepressants would result in a reduction of these pathological cellular/molecular processes and in the amelioration of symptoms, but it may also increase survival times and quality of life of patients with chronic cancer pain.