Cardiovascular and adrenaline-releasing effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin in streptozotocin diabetic rats.
ABSTRACT The 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been reported to trigger sympathoinhibition, as evidenced by its cardiovascular effects, and adrenal catecholamine secretion. The purpose of this study was to analyze the cardiovascular and adrenaline-releasing effects of 8-OH-DPAT in 1 week streptozotocin diabetic rats. 8-OH-DPAT-induced changes in mean arterial pressure (MAP) and heart rate (HR) were determined directly in anesthetized rats, whilst changes in plasma adrenaline (and plasma corticosterone and glucose) levels were analyzed in conscious rats. Resting blood pressure and heart rate were diminished in diabetics, when compared with controls. These changes were associated with a decrease in body weight and a marked increase in resting plasma glucose levels. Diabetes did not affect MAP response to 8-OH-DPAT, except for a decrease in the amplitude of MAP maximal fall, which was associated with a diminished bradycardic response to 8-OH-DPAT. Blood pressure response to prazosin (0.5 mg/kg) in 8-OH-DPAT-pretreated rats was also diminished in diabetics. Lastly, diabetes prevented the adrenaline-releasing and hyperglycemic effects of 8-OH-DPAT (250 ug/kg).
- [show abstract] [hide abstract]
ABSTRACT: The present review tries to delineate some mechanisms through which the sympathetic nervous system (SNS) and the hypothalamo-pituitary-adrenal (HPA) interact with central serotonergic systems. The recent progress in 5-hydroxytryptamine (5-HT) receptor pharmacology has helped to define the means by which central serotonergic activity may alter the respective activities of the SNS (sympathetic nerves and adrenomedulla) and of the HPA axis. These pharmacological findings have also helped to characterize the differential effects of central 5-HT upon different branches of the SNS and the numerous sites at which 5-HT exerts stimulatory influences upon the HPA axis. Although relevant to stress-related neuroendocrinology, the extent to which these interactions are involved in the antidepressant/anxiolytic properties of some serotonergic agents still remains to be clarified. Beside these findings, there is also abundant evidence for a tight control of central serotonergic systems by stress hormones. Activation of the SNS increases, by numerous means, central availability of tryptophan, whereas glucocorticoids exert differential actions upon the intra- and the extraneuronal regulation of 5-HT function. Actually, a significant number of these mechanisms is involved in the maintenance of homeostasis during stressful events, thereby conferring to these mechanisms a key role in adaptation processes.Brain Research Reviews 01/1993; 18(1):1-32. · 7.82 Impact Factor