ACTH 6-9-PGP improves memory consolidation processes in rats

Introduction: The His-Phe-Arg-Trp sequence corresponding to the 6-9th amino acid residue of the adrenocorticotropic hormone molecule (ACTH6-9) is the critical pharmacophore of all endogenous melanocortin receptor agonists. In order to effects prolongation it may be stabilized by the addition of the amino acid sequence Pro-Gly-Pro (PGP) to the C-terminus. The aim of this work was to study the effect of ACTH6-9-PGP (HFRWPGP) on the processes of memory consolidation in the model of passive avoidance conditioning in comparison with ACTH4-7-PGP effects. Materials and methods: The study was carried out on the model of passive avoidance conditioning. The effects of ACTH6-9-PGP were studied after its intraperitoneal injection to male Wistar rats at doses of 0.5, 5, 50, 150, and 450 μg/kg 15 minutes before the experiment, whereas the effects of ACTH4-7-PGP– under the similar conditions at doses of 50, 150, and 450 μg/kg. Results and discussion: It was found that ACTH6-9-PGP had a pronounced stimulating effect on the memory consolidation process in the dose range from 0.5 μg/kg to 150 μg/kg, significantly increasing the latent period of an animal entering the dark chamber. Administration of ACTH4-7-PGP led to an improvement in the consolidation processes of the acquired conditioned reflex at the doses of 50 μg/kg and 450 μg/kg. Conclusion: The range of effective doses of ACTH6-9-PGP is lower than that of ACTH4-7-PGP, which indicates the greater activity of HFRWPGP sequence in relation to memory consolidation processes and allows considering this peptide as a promising molecule for creating nootropic pharmacological drugs.

The Effect of Social Anxiety on the Acquisition and Extinction of Low-Cost Avoidance

Excessive avoidance and safety behaviours are a hallmark feature of social anxiety disorder. However, the conditioning and extinction of avoidance behaviour in social anxiety is understudied. Here, we examined the effect of individual differences in social anxiety on low-cost operant avoidance conditioning and extinction in 80 female participants. We employed an avoidance conditioning and extinction paradigm and measured skin conductance response, threat expectancy ratings and avoidance behaviour throughout the task. Findings demonstrated that elevated levels of social anxiety predicted the generalisation of conditioned avoidance responses across to safety cues during avoidance conditioning. When the opportunity to avoid was returned after extinction learning, elevated social anxiety was associated with increased avoidance behaviour to both threat and safety cues. The results suggest that compromised extinction of avoidance behaviour is a characteristic of social anxiety and supports the strategy of minimising avoidance and safety behaviours during exposure therapy for the treatment of social anxiety disorder. Future research should utilise the avoidance conditioning and extinction paradigm as a laboratory model for clinical research to investigate how, and under what circumstances, the extinction of avoidance and safety behaviours can be improved for individuals high in social anxiety.

The influence of acizol into effects of picrotoxin, injected in rat’s neostriatum

The aim of the article. The article is devoted to investigation of of zinc donator acizol influence to rat’s behavior, broken by intrastriatal injection of GABA-A receptor antagonist picrotoxin. Materials and methods. Adult male Wistar rats with avoidance conditioning reflexes in “shuttle box” and free locomotor activity in “open field” were used. Daily microinjection of picrotoxin (2 mcg/1 mcl) bilateral into rostral neostriatum in term of 15 days were made. Zinc donator acizol was injected intraperitoneal (24 mg/kg). Results. Steady losses of avoidance conditioning and choreo-mioclonic hyperkinesis of limbs and body, similar with human Huntington’s chorea by picrotoxin were produced. Acizol is contribute to restore avoidance conditioning and to prevent the development of hyperkinesis or essentially extend latency and lover duration of it. Conclusion. With the early data obtained, there is reason to propose, that acizol, to increasing the zinc content in the body, especially in the brain, is recover damaged cognitive function and to prevent the picrotoxin-induced hyperkinesis. Acizol should be proposed as perspective drug in extrapyramidal hyperkinetic deviation treatment in human.

Microglia activation in the offspring of prenatal Poly I: C exposed rats: a PET imaging and immunohistochemistry study

BackgroundThe well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinflammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid (Poly I:C) during pregnancy using 11C-PK11195 positron emission tomography (PET) and immunohistochemistry.ObjectiveThe study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats.MethodsOffspring of Poly I:C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition (PPI) and latent inhibition (LI) test (including active avoidance conditioning task and passive avoidance conditioning task). Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.ResultsThe treatment group showed hyperlocomotion and deficits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex (t=−3.990, p=0.003) and hippocampus (t=−4.462, p=0.001). The number of activated microglia cells was significantly higher in the treatment group than in the control group (hippocampus: t=8.204, p<0.001; prefrontal: t=6.995, p<0.001). Within the treatment group, there were significant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.ConclusionsThe present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.