5-hydroxytryptamine 1A receptor activation reduces cutaneous vasoconstriction and fever associated with the acute inflammatory response in rabbits.
ABSTRACT 5-Hydroxytryptamine(1A) (5-HT1A) receptor activation reduces body temperature partially by dilating the thermoregulatory cutaneous vascular bed, thereby increasing heat transfer to the environment. Constriction of this vascular bed, with consequent reduction of heat transfer to the environment, contributes to fever associated with the acute inflammatory response. Thus activation of 5-HT1A receptors might inhibit thermoregulatory cutaneous vasoconstriction and reduce the fever associated with the acute inflammatory response. The present study tested this hypothesis in conscious unrestrained rabbits. The acute inflammatory reaction was induced with i.v. lipopolysaccharide (LPS, 0.5 microg/kg). Body temperature was measured with an i.p. telemetric probe, and ear pinna blood flow was measured with a chronically implanted Doppler ultrasonic probe. 5-HT1A receptors were activated with i.v. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). LPS increased body temperature by +1.7+/-0.2 degrees C during the first hour after administration. The ear pinna Doppler blood flow signal fell from 69+/-11 to 5+/-1 cm/s within 15 min (n=7, P<0.01) and remained at a low level for approximately 1 h after LPS. When administered 45 min after LPS, 8-OH-DPAT (0.1 mg/kg i.v.) reversed this fall, increasing the Doppler signal from 6+/-1 to 55+/-7 cm/s (P<0.01, n=6), and reduced the rise in body temperature. Treatment with 8-OH-DPAT (0.1 mg/kg i.v.) 5 min before and 30 min after LPS entirely prevented the LPS-induced fall in ear pinna blood flow, and reduced the rise in body temperature from 1.7+/-0.2 degrees C to 0.7+/-0.2 (n=7, P<0.01). Treatment with WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride) (0.1 mg/kg i.v.) prevented and reversed the effects of 8-OH-DPAT. Thus activation of 5-HT1A receptors reduces thermoregulatory cutaneous vasoconstriction and fever occurring as part of the acute inflammatory response. Our findings elucidate the neurotransmitter mechanisms underlying expression of an important component of the febrile response, and suggest that drugs with 5-HT1A agonist properties might be therapeutically useful when it is clinically important to reduce this response.
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ABSTRACT: Fever is a prominent feature of diseases and is an ongoing process that is always accompanied by metabolic changes in the body system. Despite the success of temperature regulation theory, the underlying biological process remains unclear. To truly understand the nature of the febrile response, it is crucial to confirm the biomarkers during the entire biological process. In the current study, a 73-h metabolic footprint analysis of the urine from yeast-induced pyrexia rats was performed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Potential biomarkers were selected using orthogonal partial least squares-discriminate analysis (OPLS-DA), the rational biomarkers were verified by Pearson correlation analysis, and the predictive power was evaluated using receiver operator characteristic (ROC) curves. A metabolic network constructed using traditional Chinese medicine (TCM) grammar systems was used to validate the rationality of the verified biomarkers. Finally, five biomarkers, including indoleacrylic acid, 3-methyluridine, tryptophan, nicotinuric acid and PI (37:3), were confirmed as rational biomarkers because their correlation coefficients were all greater than 0.87 and because all of the correlation coefficients between any pair of these biomarkers were higher than 0.75. The areas under the ROC curves were all greater than 0.84, and their combined predictive power was considered reliable because the greatest area under the ROC curve was 0.968. A metabolic network also demonstrated the rationality of these five biomarkers. Therefore, these five metabolites can be adopted as rational biomarkers to reflect the process of the febrile response in inflammation-induced pyrexia.Journal of pharmaceutical and biomedical analysis 02/2014; 95C:68-75. · 2.45 Impact Factor
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ABSTRACT: Clinical studies suggest resting thermoregulatory cutaneous vasomotor tone could be increased in schizophrenia, resulting in reduced hand blood flow. In animal models, atypical antipsychotics including clozapine potently inhibit sympathetic neural outflow to the thermoregulatory cutaneous vascular beds. We have now determined whether antipsychotic medication administration is associated with an acute increase in hand blood flow in patients with schizophrenia and schizoaffective disorder, and whether this increase correlates with clinical status. Hand temperature was measured with an infrared camera in 12 patients with chronic schizophrenia or schizoaffective disorder 30 min prior to, then 30 and 60 min following medication. Clinical status was assessed via the Brief Psychiatric Rating Scale (BPRS). Results were compared using regression and repeated measures analysis of variance. A robust and significant increase in hand temperature (p < 0.001) was observed following antipsychotic administration. The mean increase after 60 min was 4.1 ± 2.4°C. This increase was significantly associated with colder hand temperature prior to medication (p < 0.05; suggestive of increased resting vasoconstriction) and with more severe psychiatric symptoms (p < 0.05). Atypical antipsychotics were associated with increased hand blood flow, consistent with inhibition of thermoregulatory sympathetic outflow to the cutaneous vascular bed in patients with schizophrenia and schizoaffective disorder. This increase correlated with symptom severity. Hand temperature increase following antipsychotic medication may therefore be a simple and informative physiological marker of disease activity and potential response in patients with schizophreniform disorders. Given that antipsychotics also inhibit sympathetic outflow to brown adipose tissue, which normally converts energy to heat, future studies should examine whether antipsychotic-induced hand temperature increase is associated with antipsychotic-induced weight gain.Australian and New Zealand Journal of Psychiatry 08/2011; 45(8):646-53. · 3.29 Impact Factor
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ABSTRACT: In this review, we focus on the relationship among Parkinson's disease (PD), stress and depression. Parkinson's disease patients have a high risk of developing depression, and it is possible that stress contributes to the development of both pathologies. Stress dysfunction may have a role in the etiology of preclinical non-motor symptoms of PD (such as depression) and, later in the course of the disease, may worsen motor symptoms. However, relatively few studies have examined stress or depression and the injured nigrostriatal system. This review discusses the effects of stress on neurodegeneration and depression, and their association with the symptoms and progression of PD.Experimental Neurology 01/2012; 233(1):79-86. · 4.65 Impact Factor