The role of 5-hydroxytryptamine (5-HT)1A receptor activity in prenatal ischemia was studied, by injecting 8-hydroxy-dipropylaminotetraline (8-OH-DPAT; 50 microgram/kg, s.c.), a 5-HT1A agonist on gestation day 17, and 30 min later inducing transient ischemia by ligating the uterine vessels for 30 min. On postnatal day 95, rats that had experienced prenatal ischemia showed impaired motor coordination and reduced concentration of 5-HT in the cerebellum compared with Sham-operated controls. In addition, they showed increased 5-HT1A receptor densities in the cerebral cortex. Pretreatment with 8-OH-DPAT ameliorated the behavioral and neurochemical sequelae measured in the present study. The results suggest that 5-HT1A receptors protect the brain from ischemic insult and/or facilitate recovery after prenatally experienced ischemia.
8-Hydroxy-2-(di-n-propylamino)tetralin* ; Animals ; Brain ; Cerebellum ; Cerebral Cortex ; Ischemia* ; Neuroprotective Agents* ; Pregnancy ; Rats* ; Receptor, Serotonin, 5-HT1A ; Serotonin ; Serotonin 5-HT1 Receptor Agonists

Functional nausea and vomiting is a broad term used to be described a subset of individuals who have chronic nausea and vomiting without apparent cause, despite extensive evaluation. According to the Rome III criteria, functional nausea and vomiting can be subdivided into three separate entities: chronic idiopathic nausea, functional vomiting and cyclic vomiting syndrome. Although no specific test can diagnose these diseases, the diagnostic approach requires excellent history taking combined with judicious diagnostic testing to exclude some organic cause of chronic nausea and vomiting. These conditions are probably not psychogenic in origin. Treatment remains empirical for all patients with functional nausea and vomiting. Reassurance and supportive physician-patient relationship, along with use of low-dose tricyclic antidepressants, can be beneficial in caring for patients with chronic idiopathic nausea and functional vomiting. The cornerstones of management for patients with cyclic vomiting syndrome are identifying and avoidance of triggering factors, treatment with prophylactic antimigraine agents, 5-HT3 antagonists, benzodiazepines and 5-HT1 agonists (sumatriptan), with supportive therapy.
Antidepressive Agents, Tricyclic ; Benzodiazepines ; Diagnostic Tests, Routine ; Humans ; Nausea ; Rome ; Serotonin 5-HT1 Receptor Agonists ; Serotonin 5-HT3 Receptor Antagonists ; Vomiting

It has been known that central tryptaminergic system is closely related with the regulation of renal function, and that central 5-HT1 receptors mediate diuresis and natriuresis, whereas central 5-HT2 and 5-HT3 receptors mediate antidiuresis and antinatriuresis. Among many subtypes of 5-HT1 receptors, central 5-HT1A subtype has been suggested to exert diuretic and natriuretic effets. Further, it was recently observed that TFMPP, 5-HT1B agonist, elicited profound diuresis and natriuresis when administered intracerebroventricularly(icv). Present study is therefore undertaken to delineate the mechanism involved in the natriuresis and diuresis induced by icv TFMPP, employing the denervated and vagotomized rabbits. The influence of icv TFMPP on the plasma level of ANP was also observed. TFMPP 250 microgram/kg icv produced marked diuresis and natriuresis. Renal hemodynamics showed significant increase only in the first 10-min period after administration and thereafter tended to recover. However, natriuretic action lasted even after the increased renal hemodynamics returned to the control level, suggesting the decreased Na reabsorption in the tubules by humoral natriuretic factors. Systemic blood pressure transiently increased. In rabbits in which one kidney is denervated, with the contralateral intact as the control kidney, the denervated kidney also responded with natriuresis and diuresis like that of the normal rabbit. The contralateral kidney responded with typical diuretic and natriuretic effects, along with the marked increased of renal hemodynamics. The plasma ANP, one of humoral natriuretic factors, increased after administration of icv TFMPP, peaking at about 15min. In bilaterally vagotomized rabbits, the natriuretic and diuretic effects produced by icv TFMPP were greater than that of the normal rabbits. These observations suggest that the natriuresis and diuresis elicited by icv TFMPP result from the inhibition of tubular Na reabsorption mainly through mediation of ANP. It has been also suggested that vagus nerve might exert inhibitory influence on the diuretic action of icv TFMPP, because the renal effects was augmented in the vagotomized rabbits.
Atrial Natriuretic Factor ; Blood Pressure ; Diuresis ; Diuretics ; Hemodynamics ; Kidney ; Natriuresis ; Natriuretic Agents ; Negotiating ; Plasma ; Rabbits* ; Receptors, Serotonin, 5-HT1 ; Receptors, Serotonin, 5-HT3 ; Serotonin 5-HT1 Receptor Agonists ; Vagus Nerve

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the 5HT2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ondansetron but was inhibited by the 5-HT1 receptor antagonist methysergide and 5-HT4 receptor antagonist GR113808. These results indicate that 5-HT1 and 5-HT4 receptors may mediate the contraction of the 5-HT-induced response and 5-HT2 and 5-HT3 receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.
Atropine ; Benzamides ; Contracts ; Gastrointestinal Tract ; Guanethidine ; Ileum ; Indoles ; Ketanserin ; Methysergide ; Morpholines ; Muscle Contraction ; Muscle, Smooth ; Muscles ; Ondansetron ; Receptors, Serotonin ; Receptors, Serotonin, 5-HT1 ; Receptors, Serotonin, 5-HT3 ; Receptors, Serotonin, 5-HT4 ; Relaxation ; Serotonin ; Serotonin Receptor Agonists ; Sulfonamides ; Tetrodotoxin

BACKGROUND AND OBJECTIVES: This study was aimed to explore the effects of the 5-hydroxytryptamine (5-HT) on potassium currents in rat vestibular nuclear neurons. MATERIALS AND METHOD: Sprague-Dawley rats aged 14 to 16 days were anesthetized with ether and decapitated. After enzymatic digestion, the portion of medial vestibular nucleus neuron was removed by micropunching and gently agitated. The dissociated neurons were transferred into a recording chamber mounted on an inverted microscope and whole-cell membrane currents were recorded at room temperature by using standard patch-clamp techniques. RESULTS: When cells were held at -70 mV and depolarized from -60 mV to +40 mV in 10 mV increments, sustained outward potassium currents were evoked. The response of medial vestibular nuclear neurons to 5-HT was not uniform. The outward potassium currents were increased in 17 of 40 cells and decreased in 23 of 40 cells. 5-carboxamidotryptamine, 5-HT1 agonist increased the outward potassium currents of the medial vestibular nuclear cell. alpha-methyl-5-hydroxytryptamine, 5-HT2 agonist decreased the outward potassium currents of the medial vestibular nuclear cell. CONCLUSION: These results suggest that 5-HT affects the potassium currents of the cell with different effects according to the receptor subtype on which it acts.
Animals ; Digestion ; Dihydroergotamine ; Ether ; Membranes ; Neurons* ; Patch-Clamp Techniques ; Potassium Channels ; Potassium* ; Rats* ; Rats, Sprague-Dawley ; Serotonin 5-HT1 Receptor Agonists ; Serotonin 5-HT2 Receptor Agonists ; Serotonin* ; Vestibular Nuclei

OBJECTIVE: Post weanling isolation-reared (IR) rats are featured with depressive phenotype, yet its mechanism is not clearly defined particularly in terms of the involvement of central 5-HT1A receptors. The present study aims to examine the effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT depletion. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14 days after the surgery, rats were assessed their performance in FST with or without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY). RESULTS: 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC rats. IR rats were more immobile and less sensitive to the lesion-induced immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7-DHT lesion increased the expression of PFC 5-HT1A receptors. CONCLUSION: The integrity of central 5-HT system is developmentally crucial for the 5-HT1A-relevant depression profile in rats of social isolation.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Amygdala ; Animals ; Depression* ; Hippocampus ; Phenotype ; Prefrontal Cortex ; Rats* ; Receptor, Serotonin, 5-HT1A ; Serotonin 5-HT1 Receptor Agonists ; Serotonin* ; Social Control, Formal ; Social Isolation

OBJECTIVE: Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT. Seven days later rats entered a protocol of 8-OH-DPAT, a 5-HT1A agonist, in which locomotor activity, ASR and PPI and their tissue levels of 5-HT were measured. RESULTS: Our results found that both IR and 5,7-DHT decreased the tissue concentration of 5-HT. IR-induced hyperactivity and gating impairment were unaffected by 5-HT depletion. 8-OH-DPAT strengthened the ASR in IR but not SOC rats and the drug-reduced PPI could be adjusted by 5,7-DHT pretreatment. 8-OH-DPAT at 100 μg/kg enhanced PPI in 5-HT-depleted SOC rats. However for IR rats, 8-OH-DPAT strengthened PPI in sham rats but downgraded it in depletion condition. CONCLUSION: The integrity of central 5-HT system is important to 5-HT1A-modulated sensorimotor gating in isolation-reared rats.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Acoustics ; Animals ; Motor Activity ; Prepulse Inhibition ; Rats ; Receptor, Serotonin, 5-HT1A ; Reflex, Startle ; Sensory Gating ; Serotonin ; Serotonin 5-HT1 Receptor Agonists ; Social Control, Formal