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The main goal of current projest is the study of interaction of two widely distributed neurotransmitter systems - endocannabinoid (EC) ja cholescystokinin (CCK) - in the regulation of emotional stress. The function of EC system will be studied in the genetically modified mice with the altered function of CCK-ergic system (mice lacking CCK2 receptors and mice over-expressing prepor-CCK gene). In these mice the effects of CB1 agonists and antagonists will be studied in the behavioural models reflecting the emotional stress. The expression patterns of genes of CB1 receptors and enzymes involved in the metabolism of ECs will be studied in the brain structures of these animals. The changes in the activity of CCK- and gamma-aminobutyric(GABA)-ergic systems will be studied in the brain of mice, lacking enzymes involved in the synthesis of ECs (anandamide and 2-arachidonoyl-glycerol). Moreover, the expression patterns of EC-, CCK- and GABA-related genes will be studied in the brain structures of rats exposed to the emotional stress (exposure to the elevated zero-maze and cat odour, induction of neuropathic pain and social isolation). Based on the data of EC and CCK interaction the rationale approach will be developed for the prevention and diminishing of negative impact of emotional stress. |