EFFECTS OF ADENOSINE RECEPTOR LIGANDS ON THE NOCICEPTION AND STRESS-INDUCED ANTINOCICEPTION IN MICE

Introduction: It is well known that exposure to different stressors caused a sequence of biochemical, physiological and behavioural changes including analgesia which is realised by activating multiple endogenous pain inhibitory systems. Although the existing data reveal the important role of the adenosine modulatory system in the processing of nociceptive information, scarce data are available for its role in stress-induced changes in nociception. Materials and Methods: Male ICR mice – controls and exposed to acute (120 minutes) restraint stress (RS) were used; Acetic acid-induced nociception (writhing test); Adenosine A1 receptor agonist N6-R phenylisopropil-adenosine (R-PIA, 0.5 mg/kg, intraperitoneally, IP), nonselective adenosine receptor antagonist theophylline (acute 75mg/kg, IP and chronic 75 mg/kg/day/14 days, IP). Results: RS and R-PIA decreased the visceral nociception in mice. Acute and chronic treatment with theophylline did not influence the pain reactions neither in nonstressed nor in stressed animals. R-PIA administered before restraint stress fully reversed stress–induced antinociception. Single dose of theophylline antagonized the effects of R-PIA both in nonstressed and stressed animals. Chronic theophylline did not antagonize the antinociceptive effect of R-PIA, but abolished R-PIA induced reversion of SIA. Conclusion: Endogenous adenosine is not able to change the RS-induced visceral antinociception, as theophylline did not show any effects on the stress. However, adenosine A1 receptors are involved both in the antinociception in the healthy mice and RS-induced antinociception, perhaps by different mechanism

Immunohistochemical study on distribution of cannabinoid cb1 receptors in the rat`s prefrontal cortex after cold stress procedure

The prefrontal cortex (PFC), which mediates the emotional coping response to different stressful paradigms, is composed of distinct parts depends on stimulus involved physical or psychological stress. It also plays a role in a number of neurological conditions. It`s known that neuroendocrine control of homeostatic and reproductive functions including stress response and energy metabolism is fulfils by important signaling molecules as endogenous cannabinoids. The aim of the present study was to examine the effects of cold stress on distribution of CB1- receptors in PFC of rats. Immunohistochemical procedure for CB1-receptors was performed in adult male Wistar rats. The data were entered in the computer program, recorded automatically, calculated and compared by Student`s t-test. We found CB1-immunoreaction in axons and dendrites as well as in cell bodies where they presented as puncta on somata. The cells bodies were comprised of several distinct shapes: pyramidal, oval, fusiform and multipolar. Numerous fine-beaded fibers and puncta were seen on a handful of pyramidal large-sized neurons and many puncta were observed around the oval-shaped small- and medium-sized neurons.The PFC in cold stress rats demonstrated around 18% higher density of CB1-receptors compared with controls. In conclusion our results showed that cold stress exposure increased distribution of CB1-receptors in PFC of rats. These experimental data suggest that endocannabinoid system in this brain area may play an important role in the continuity of homeostasis in cold stress

Effects of the antinociceptive dipeptide L-tyrosine-L-arginine (kyotorphin) on the motivation, anxiety, and memory in rats

Introduction: The endogenous dipeptide L-tyrosine-L-arginine (kyotorphin, KTP) is found in brain structures related to the processing of information for nociception, the control of emotions, and memory formation. Besides the antinociceptive effect of KTP, it has a mild protective activity against the deleterious influence of the brain hypoperfusion and streptozotocin on the behavior and memory. Aim: We aimed to study the effects of the intracerebroventricular injection of effective antinociceptive doses of KTP on the motivational behavior, memory, and blood and hippocampal levels of the carbonylated proteins in healthy male adult Wistar rats.Materials and methods: We used a paw-pressure test for assessment of acute nociception, an open field test for assessment of exploration and habituation to a new environment, elevated plus maze test for the evaluation of anxiety-like behavior, and novel object recognition test for working memory. Carbonylated protein assay was used for the assessment of the oxidative impairment of the proteins. The results were analyzed by ANOVA.Results: The present data showed that all single doses of KTP exerted an antinociceptive effect, but this effect was not observed after chronic administration. Only the highest dose of 100 µg was able to induce anxiolytic and motor inhibiting effects. None of the doses used showed effects on the recognition memory or the level of the carbonylated protein. Conclusion: Our results showed that KTP exerted its antinociceptive effect without affecting negatively the blood and brain carbonylated protein or basic behavioral parameters related to the exploration, motivation, and memory formation in healthy rats