Attenuation of 8-OH-DPAT-induced decreases in 5-Ht synthesis in brain regions of rats adapted to a repeated stress schedule.
ABSTRACT Previously it has been shown that single episode of 2 h restraint produced behavioral deficits in rats which were not observed following daily restraint period of 2h/day for 5 days. It was suggested that adaptation to a stress schedule develops when the similar stress is administered repeatedly. In view of a role of 5-hydroxytryptamine (5-HT) in adaptation to stress the present study concerns effects of a 5-HT-1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on the synthesis of 5-HT in brain regions of rats adapted to a repeated restraint stress schedule of 2h/day for 5 days. The drug injected systemically at a dose of 1 mg/kg decreased 5-HT synthesis in the hypothalamus, cortex, hippocampus, striatum and raphe regions of previously unrestrained rats. These decreases were either smaller (raphe) or not observed (hypothalamus, cortex and hippocampus) in most brain regions of rats adapted to the repeated restraint stress schedule of 2h/day for 5 days. These results suggest that a subsensitive negative feedback effect on the synthesis of 5-HT leading to an increase in synaptic 5-HT concentration might help coping with stress demand to produce adaptation to stress.
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ABSTRACT: Serotonin (5-hydroxytryptamine, 5-HT), acting via the hippocampus, is thought to be critical for the neuroadaptation that alleviates the adverse effects of stress on emotion and behavior. It was hypothesized that a decrease in raphe-hippocampal serotonin neurotransmission caused by exaggerated feedback inhibition of 5-HT synthesis and release significantly contributes to stress-induced behavioral deficits. Acute exposure to 2 h of restraint stress increased 5-HT metabolism in the cortex and raphe region but had no such effect in the hippocampus. Exposure to 2 h of restraint stress elicited anxiety-like behavior, which was monitored in the light-dark transition test the next day. Animals sacrificed 24 h after termination of the stress period exhibited a decrease in the concentration of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus but not in the cortex and raphe. 8-Hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT) injected at doses of 0.125, 0.25 and 0.5 mg/kg decreased 5-HT metabolism in the raphe, cortex and hippocampus of restrained and unrestrained animals, and the decreases in the raphe and hippocampus, but not those in the cortex, were greater in restrained than unrestrained animals. Exaggerated feedback control over raphe-hippocampal serotonin neurotransmission may be involved in the inability of the organism to cope with increased stress and elicits behavioral depression.Pharmacological reports: PR 01/2011; 63(4):888-97. · 1.97 Impact Factor
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ABSTRACT: Neurotransmission by serotonin (5-HT) is tightly regulated by several autoreceptors that fine-tune serotonergic neurotransmission through negative feedback inhibition at the cell bodies (predominantly 5-HT(1A)) or at the axon terminals (predominantly 5-HT(1B)); however, more subtle roles for 5-HT(1D) and 5-HT(2B) autoreceptors have also been detected. This review provides an overview of 5-HT autoreceptors, focusing on their contribution in animal behavioral models of stress and emotion. Experiments targeting 5-HT autoreceptors in awake, behaving animals have generally shown that increasing autoreceptor feedback is anxiolytic and rewarding, while enhanced 5-HT function is aversive and anxiogenic; however, the role of serotonergic activity in behavioral models of helplessness is more complex. The prevailing model suggests that 5-HT autoreceptors become desensitized in response to stress exposure and antidepressant administration, two seemingly opposite manipulations. Thus there are still unresolved questions regarding the role of these receptors-and serotonin in general-in normal and pathological states.Journal of chemical neuroanatomy 05/2011; 41(4):234-46. · 1.75 Impact Factor
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ABSTRACT: Stress is the major predisposing and precipitating factor in the onset of depression which is the most significant mental health risk for women. Behavioral studies in animal models show that female sex though less affected by an acute stressor; exposure to repeated stressors induces coping deficits to impair adaptation in them. A decrease in the function of 5-hydroxytryptamine (5-HT; serotonin) in the hippocampus and an increased function of the 5-HT-1A receptor in the raphe nucleus coexist in depression. Pharmacological and neurochemical data are relevant that facilitation of serotonin neurotransmission via hippocampus due to desensitization of somatodendritic 5-HT1A receptors may lead to adaptation to stress. The present article reviews research on sex related differences of raphe-hippocampal serotonin neurotransmission to find a possible answer that may account for the sex differences of adaptation to stress reported in preclinical research and greater incidence of depression in women than men.DNA research: an international journal for rapid publication of reports on genes and genomes 09/2011; 9(3):512-21. · 1.73 Impact Factor