The Relationship Between DA,GABA In Orbital Frontal Cortex And Depression And The Expression Of NPY,PAM,Kalirin In OFC And Hippocampus

Abstract: With the modem social pace, the greater social pressure which people have to face results in more and more depression. Depression is a mental disorder especially with low spirits. The high incidence of depression is related to the stressful life events come from the quickened social rhythm, Stress is an unspecific adaptive response when animals are confronted with various stimulus. The stress in some frequency and intensity would make obstacle in mood and cognition on animals, even depression. The mechanism that the stress induces depression involved many neurotransmitter in several areas in the brain, to discuss the mechanism how DA and GABA work in depression, the study targets OFC(orbital frontal crtex) which relate to the mood and cognition, select male SD rats and adopt forced swimming test(forced swimming test ) to construct animal depression model, microinject drugs into OFC, and OFT(open field test),FST to test behavior. We researched the relationship of the two neurotransmitters in stress and the approach that their receptors composed; and we also use immunohistochemistry to observed the expression of NPY (neuropeptideY), PAM( peptidylglycine alpha-hydroxylating monooxygenase) and Kalirin in OFC and hippocampus after microinjection in OFC. We make the expression of the three factors as the standard to know the neuroplasticity in disorder of the neurotransmitter. To find more evidence for the research of the depression.The results are as follows:1. The relationship of the DA, GABA and their involved receptors with the stressful depression(n=10):(1). After microinjecting DA and GABA into OFC, rats' immobility time is reduced significantly(P＜0.05), in OFT, group DA's times of standing and grooming,group GABA's displacement increases significantly compared with the Saline group(P＜0.05). There is no other significant changes in these groups. (p＞0.05) (2). group SCH+DA' immobility time is greater than group DA significantly(P＜0.05), no greater change compared with group Saline.Group BM+DA' immobility time is greater than group GABA significantly, shorter than group Saline significantly; group SCH+GABA' immobility time is greater than group GABA, no greater change compared with the Saline group, group SCH+GABA 'displacement in OFT reduced compared with the group GABA.2. After microinjecting DA, GABA and involved receptor' antagonism into OFC, the change of expression of NPY,PAM,Kalirin in OFC and hippocampus(n=3):(1). Group Saline' expression of NPY,PAM,Kalirin in OFC and hippocampus decreased compared with group control(P＜0.05);(2). In OFC, group DA' expression of NPY increased compared with group Saline, group DA+SCH' expression of NPY decreased compared with group DA, group DA+BM' expression of NPY increased compared with group DA; the expression of the PAM and Kalirin has not similar change tendency;(3). In hippocampus, group DA+BM' expression of NPY increased compared with group DA+SCH; group DA' expression of Kalirin increased compared with group Saline, group DA+SCH' expression of Kalirin decreased compared with group DA, group GABA' expression of Kalirin decreased compared with group Saline and group GABA+BM(P＜0.01).From the above results, We conclude that:1. The different behavior in FST and OFT have the same neurobiology basis but maybe have the different neural mechanism.2. Microinjecting DA and GABA into OFC could reduce the depressive behavior, DIR could mediate the anti-depression of the DA, GABAAR could mediate the anti-depression of the GABA, D₁R could mediate the anti-depression of the GABA, GABA inhibit the anti-depression of DA through the GABA_AR, which suggest the anti-depression of GABA maybe is through GABA-A ang modulating the dopaminergic neuron(DAergic neuron). GABAergic neuron maybe affect DAergic neuron by presynaptic facilitating the release of DA and inhibiting the D1 receptor through presynaptic inhibition, which consis of the pathway.3. The decrease of NPY in OFC and hippocampus is involved in the depression; The coming on of the depression is probably involved the plastic of OFC and hippocampus, there the graduation that first function then structure. The antidepression of the DA in OFC involved the NPY, The DA in OFC could mediate the stressful disorder of NPY in OFC, the target may be not PAM.4. DA in OFC increase the expression of Kalirin in hippocampus through D1 receptor, Which maintain the function and structure of hippocampus neurons. The stressful depression is involved the disorder of the DA and GABA in OFC and the decreaseing expression of Kalirin, retrogression of neurons.