Attenuation of 8-OH-DPAT-induced decreases in 5-HT synthesis in brain regions of rats adapted to a repeated stress schedule

Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Unit, University of Karachi, Karachi 75270, Pakistan.
Stress (Impact Factor: 2.72). 01/2000; 3(2):123-9. DOI: 10.3109/10253899909001117
Source: PubMed


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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    • "Stress can be acute, induced by a 'one-time' or a 'single stress' exposure, whereas chronic, predictable or unpredictable , stress refers to either prolonged or repeated exposure over a longer period of time. Repeated exposure to a predictable stressor produces adaptive changes or habituation to the stressor (Haleem, 1999, 2011), resulting in a decrease in the stress response, as indicated by a reduction in the stress-induced increase of plasma corticosterone (Haleem et al., 1988). Habituation effects are also produced following exposure to a stressor for a very short duration. "
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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 · 2.15 Impact Factor
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    • "Previously it was reported that restrained induced increase of serotonin metabolism were smaller in sugar rice bran treated rats (Jabeen and Haleem, 2008; Inam et al., 2009). It is, however, possible that long term increase of sugar rich diet might decreased the efficacy of negative feedback control over the synthesis and release of 5-HT (Haleem, 1999; Inam et al., 2008). Long term consumption of sugar diet decreased the effectiveness of presynaptic as well as postsynaptic 5-HT 1A receptor dependent responses (Inam et al., 2006). "
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    ABSTRACT: Stress produces behavioral and neurochemical deficits. To study the relationship between adaptation to stress and macronutrient intake, the present study was designed to monitor the effects of different diets on feed intake, growth rate and serotonin (5-Hydroxytryptamine, 5-HT) metabolism following exposure to restraint stress in rats. Rats were divided into four groups (n=12) as control, sugar, protein and fat rich diet fed rats. After 5 weeks of treatment animals of each group were divided into unrestrained and restrained animals (n=6). Rats of restrained group were given immobilization stress for 2 hours/day for 5 days. Food intake and growth rates of unrestrained and restrained rats were monitored daily. Rats were decapitated on 6 th day to collect brain samples for neurochemical estimation. Results show that sugar diet fed rats produced adaptation to stress early as compared to normal diet fed rats. Food intake and growth rates of unrestrained and restrained rats were comparable on 3 rd day in sugar diet fed rats and on 4 th day in normal diet fed rats. Stress decreased food intake and growth rates of protein and fat treated rats. Repeated stress did not alter brain 5-HT and 5-HIAA levels of normal diet fed rats and sugar diet fed rats. Protein diet fed restrained rats showed elevated brain 5-HT levels. Fat diet fed restrained rats significantly decreased brain TRP and 5-HIAA levels. Finding suggested that carbohydrate diet might protect against stressful conditions. Study also showed that nutritional status could alter different behaviors in response to a stressful environment. ©2011 PVJ. All rights reserved To Cite This Article: Moin S, S Haider, S Khaliq, S Tabassum and DJ Haleem, 2012. Behavioral and neurochemical studies in stressed and unstressed rats fed on protein, carbohydrate and fat rich diet. Pak Vet J, xx(x): xxx.
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    • "Studies using learned helplessness model of anxiety/depression and chronic stress model of depression also support the role of 5-HT-1A receptor in adaptation to stress. Thus, rats adapted to repeated restrain stress schedule of 2h/day for 5 days exhibited a decrease in the sensitivity of somatodendritic 5-HT-1A [60, 104] and terminal 5-HT-1B [105] receptors: an effect similar to antidepressant like effect. It was suggested that a decrease in the negative feedback control due to desensitization of auto receptors increases the availability of 5-HT in terminal regions to help cope the stress demand and produce adaptation to stress (Fig 2). "
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