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: Stress is defined as a state that can threaten homeostasis in an organism to initiate the adaptive process. Stress mediators, which include the classic neuroendocrine hormones and a number of neurotransmitters, cytokines, and growth factors, regulate both basal and threatened homeostasis to help control the stress. Severity of stress, as well as malfunctioning of stress pathways, may impair its controllability, leading to the pathogenesis of psychiatric illnesses including depression. Leptin was initially identified as an antiobesity hormone, acting as a negative feedback adiposity signal to control energy homeostasis by binding to its receptors in the hypothalamus. Accumulating evidence has expanded the function of leptin from the control of energy balance to the regulation of other physiological and psychological processes. The aim of this paper is to evaluate the potential role of leptin in stress controllability. To this end, studies on the role of leptin in stress-induced activation of the hypothalamus-pituitary-adrenocortical axis, feeding behavior, learned helplessness, and other depression models have been accumulated. The knowledge accumulated in this article may facilitate the development of alternative treatment strategies, beyond serotonin and noradrenaline reuptake inhibition, for psychiatric care and stress-related disorders.Behavioural Pharmacology 07/2014; 25(5-6). DOI:10.1097/FBP.0000000000000050 · 2.19 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. DOI:10.1016/j.jchemneu.2011.05.001 · 2.52 Impact Factor
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ABSTRACT: The present study concerns the effectiveness of a selective 5-hydroxytryptamine (5-HT)-1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in long term sugar diet treated rats. Male albino wistar rats were divided into control and test groups. Test animals were given sugar (5 g/10 ml water) orally for three weeks. Food intakes and body weight of all rats were measured weekly. After three weeks control and test animals were further divided into two groups i.e. saline injected and drug injected. 8-OH-DPAT at a dose of 0.25mg/Kg was injected to a group of normal diet treated and another group of sugar diet treated rats. Other two groups were injected with saline. 5-HT syndrome and food intakes at 2h and 4h were monitored. Then animals were decapitated to collect brain samples for the estimation of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels by HPLC-EC method. We observed that weekly cumulative food intakes increased and body weights decreased in sugar diet treated rats. 8-OH-DPAT produced hyperactivity syndrome in both control and sugar treated rats. But these values were smaller in sugar diet than normal diet treated rats. Hyperphagic effects of 8-OH-DPAT were greater in normal diet than sugar diet treated rats. 5-HT and 5-HIAA levels were not altered. The results suggesting a desensitization of pre as well as postsynaptic 5-HT-1A receptors in rats treated with sugar diet are discussed in the context of a role of sugar diet in the precipitation of obesity and other neuropsychiatric illnesses.Pakistan journal of pharmaceutical sciences 11/2008; 21(4):327-32. · 0.95 Impact Factor