| Depression, as a mood disorder, holds the highest rate of explosion among various mental diseases nowadays. Stress is one of the main factors causing depression. Although there have been many reports on stress-induced depression, the definite mechanism is still unknown. Animal models of Behavioral Despair, Learned Helplessness, and Chronic Stress, etc., are widely used to study stress-induced depression. Addiction resulted from drug abuse has close relation to stress and mood disorders (e.g., depression). Theories concerning drug addiction dominantly consist of Hedonics, Abnormal Learning, Motivation-sensitization and Dysfunction of Prefrontal Cortex. Models of Self-administration and Conditioned Place Preference (CPP) are often applied to study drug addiction. Previous researches indicated that stress might facilitate drug addiction and intensify behavior of seeking and desiring of drugs. However, relations between different types of stress and addiction, different styles of addiction and depression, and their neural mechanism are not understood yet. To make sure of their relation and mechanism will not only enrich research theories of function of brain but also provide us references to cure depression or drug addicts, especially druggers.There are two parts in this research work.1. After Saline (0.5μl/rat), GABA (20μmol/0.5μl/rat), bicuculline (BM: specific GABAAreceptor antagonist, 0.5μmol /0.25μl/rat)+ GABA (20μmol /0.25μl/rat) , were microinjected into rats' orbital frontal cortex (OFC) , rats were tested by depression model of forced swimming test (FST). The results indicated that microinjection of GABA into OFC could significantly shorten rats' swimming immobility time (n=8, P<0.05), which could be blocked by BM (n=6, P<0.05). In conclusion, GABA in rats' OFC might play the role of antidepressant mediated by GABAa receptor. It was presumed that this effect of GABA in OFC might be completed by inhibiting the activity of other neurons in this area or directly regulating the limbic-loop of emotion involved in other brain areas and that stress-induced depression may be relevant to thefunction deficit of GABA-nergic neurons and /or down-regulation of GABAa in OFC area, however further work was required to explore the concrete neural mechanism and interactions of different neural circuits.2. Firstly, animal models of depression were made by chronic unpredicted mild stress (CUMS) , and then CPP was examined combined with morphine addicting CPP model, aiming to understand the influence of certain degree of stress stimulation or depression on morphine addiction and to clarify their relation as well. Final results demonstrated that on the one hand, a rat's depression model based on CUMS could be tested with parameters of open field test (OFT), FST, and weight loss (WL), etc., but not tested by sucrose preference test (SPT). Imipramine, an antidepressant, could reverse the effects of CUMS on FST and WL and didn't do so on OFT and SPT, which were consistent with most conclusions previously made, yet contrary to some others. In general, it was basically scientific and reliable to make a rat's depression model with CUMS method. On the other hand, the CPP results demonstrated the facts as the following.1) The total time of rats' staying at positive chambers (morphine dependent) in CUMS treated group (SS group) was shorter than that of control group (SN group) during ten-day morphine withdrawal. There was no difference of staying time of SS group between in positive chambers and in negative chambers (saline dependent), and the rats' withdrawal behaviors such as locomotion, rearing in positive chambers and negative ones was no distinctness, which were different from control group. But the numbers of wet dog in SS group were not discrepant in positive and negative chambers, the result of which accorded with that in control group.2) The total time of rats' staying at positive chambers in antidepressant imipramine treated group (IN group) was shorter than that of control group (SN group) during ten-day morphine withdrawal. In IN group, the total time of rats' staying at positive chambers was longer than that of negative chambers. And the discrepancy just happened as it did in control group. Frequencies of rats' withdrawal behavior such as locomotion and rearing in IN group in positive chambers were more than those in negative ones, no number discrepancy of wet dog being observed in these two opposite chambers, which was identical to control group.3) Total staying periods of rats in imipramine + CUMS group (IS group) at positive chambers were not different from those in SN group. In IS group, consistently... |
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