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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies determined whether serotonin 5-HT1A receptor-mediated function is modified by chronic exposure to antidepressants. Hormone responses to the 5-HT1A agonist, 8-OH-DPAT, were evaluated after long-term exposure to two antidepressants, the 5-HT uptake blocker, fluoxetine, and the norepinephrine uptake blocker, desipramine (DMI). In addition, the density and affinity of 5-HT1A receptors in the hypothalamus and cerebral cortex were measured. Male rats received fluoxetine (10 mg/kg i.p.), DMI (5 mg/kg i.p.) or saline injections once daily for 21 days. 8-OH-DPAT (0-500 micrograms/kg s.c.) was administered 18 h after the final antidepressant injection and 15 min before sacrifice. 8-OH-DPAT significantly increased plasma ACTH, corticosterone, oxytocin and prolactin, but not renin or vasopressin concentrations. Chronic injections of fluoxetine inhibited the ACTH, corticosterone and oxytocin responses to 8-OH-DPAT, suggesting reduced 5-HT1A receptor function. In contrast, chronic DMI did not alter the hormone responses to 8-OH-DPAT. The density and affinity of 5-HT1A receptors in the frontal cortex or hypothalamus were not altered by either fluoxetine or DMI. To verify that the observed effects require prolonged exposure to fluoxetine, rats received a single injection of fluoxetine (10 mg/kg, i.p.), 3 h before 8-OH-DPAT (0-500 micrograms/kg s.c.). Acute fluoxetine did not reduce any of the hormone responses to 8-OH-DPAT. In conclusion, the results suggest that chronic, but not acute, exposure to fluoxetine decreases 5-HT1A receptor function. This effect is not seen in rats chronically exposed to DMI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term fluoxetine, but not desipramine, inhibits the ACTH and oxytocin responses to the 5-HT1A agonist, 8-OH-DPAT, in male rats. 811 81

Previous reports from this laboratory have shown that pindolol, a partial serotonin1A receptor agonist, inhibited prolactin, but not cortisol secretion induced by administration of the serotonin (5-HT) precursor L-5-hydroxytryptophan or the direct-acting 5-HT2A/5HT2C receptor agonist MK-212. The findings suggest additive or interactive effects of 5-HT1A and 5-HT2A/5-HT2C receptors in modulating 5-HT-related prolactin, but not cortisol, responsivity. To examine further the role of 5-HT1A and 5-HT2A/5-HT2C receptors in prolactin and cortisol secretion in healthy men, the effects of meta-chlorophenylpiperazine (mCPP), a potent 5-HT receptor agonist, on the above hormones were studied in eight healthy men with and without pindolol pretreatment. It has previously been demonstrated that ketanserin, a 5-HT2A antagonist, and ritanserin, a 5-HT2A/5-HT2C antagonist, block the prolactin and attenuate the hypothalamic-pituitary-adrenal axis responses to mCPP in man or rodents. Administration of mCPP induced a significant increase in plasma concentrations of prolactin and cortisol. The mCPP-induced prolactin concentrations were significantly blocked by pretreatment with pindolol, whereas mCPP-stimulated cortisol levels were not diminished by pindolol pretreatment. Thus, mCPP-induced prolactin secretion appears to require the availability of both 5-HT2C and 5-HT1A receptor activation, since blockade of either of these receptors may diminish the mCPP-induced prolactin response. Cortisol secretion stimulated by mCPP may occur following 5-HT2C receptor stimulation in the presence of 5-HT1A receptor blockade.
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PMID:Pindolol pretreatment blocks stimulation by meta-chlorophenylpiperazine of prolactin but not cortisol secretion in normal men. 857 Jul 72

The effects of the selective 5-HT1A receptor agonist flesinoxan on neuroendocrine function, temperature, and behavior were assessed in male healthy volunteers using a double-blind, placebo-controlled crossover design. Flesinoxan (7 and 14 micrograms/kg), administered intravenously in 11 healthy volunteers, elicited a dose-related decrease in body temperature and increases in growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and prolactin plasma levels. In a second independent study, 12 healthy volunteers were pretreated sequentially, at one-week intervals, with either the 5-HT1A antagonist pindolol (30 mg, PO), the nonselective 5-HT1/2 antagonist methysergide (4 mg, PO), or placebo, prior to being administered flesinoxan (1 mg, IV). The growth hormone response to flesinoxan was blocked by pindolol but not by methysergide, whereas the prolactin response was blocked by methysergide but not by pindolol. The ACTH and cortisol responses to flesinoxan were potentiated by methysergide. The flesinoxan-induced hypothermia was attenuated by both methysergide and pindolol, although the latter effects did not reach statistical significance. The present results suggest that the growth hormone response and the hypothermic response to the intravenous infusion of flesinoxan may serve as a valid index of 5-HT1A receptor function in humans.
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PMID:Serotonin1A receptor activation by flesinoxan in humans. Body temperature and neuroendocrine responses. 859 27

The prevailing neurochemical theory about biological correlates of suicidal behavior focuses on the serotonergic system. In this study, we assessed the cortisol, ACTH, GH, prolactin and temperature responses to flesinoxan, a5-HT1A agonist, in 30 DSM-III-R major depressed inpatients subgrouped into suicide attempters (n = 15) and nonattempters (n = 15). The patients were assessed after a drug-free period of at least 3 weeks. A subsample of 16 patients completed the Buss-Durkee Hostility Inventory as a measure of impulsive aggressive behavior. Mean delta cortisol responses to flesinoxan were significantly lower in the group of depressed patients with a history of suicide attempts than in the group without history of suicidal behavior: for the delta cortisol values 14.5 +/- 16.3 micrograms/l vs 101 +/- 94 micrograms/l (F = 8.9, df = 5.25, p = 0.006). There was also a very significant difference between suicide attempters and nonattempters for the temperature (delta T degrees) responses to flesinoxan: 0.20 +/- 0.24 degrees C vs. 0.60 +/- 0.24 degrees C (F = 18.1, df = 5.25, p = 0.0003). Hormonal and temperature responses to flesinoxan were not correlated with BDHI irritability or assault subscale scores. The results of the present study support the implication of the serotonergic system, particularly 5-HT1A receptors, in the control of self-directed aggressive behavior. Moreover, in depressed patients, serotonergic abnormalities do not appear to be related to aggressive behavior.
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PMID:The flesinoxan 5-HT1A receptor challenge in major depression and suicidal behavior. 861 6

Drugs that, directly or indirectly produce activation of serotonin (5-HT) receptors increase plasma concentrations of both prolactin and renin. The serotonergic regulation of prolactin and renin secretion share several common characteristics. Serotonergic neurons originating in the dorsal raphe and terminating in the hypothalamus stimulate the secretion of both prolactin and renin. Destruction of cells in the hypothalamic paraventricular nucleus (PVN) inhibits both the prolactin and renin responses to 5-HT agonists and 5-HT-releasing drugs. Activation of 5-HT2 receptors increases the secretion of both prolactin and renin, while activation of other 5-HT receptor subtypes has differential effects on these hormones. However, there are also differences between the serotonergic mechanisms that regulate the secretion of prolactin and renin. Activation of 5-HT1A receptors increases the secretion of prolactin but not of renin. In addition, activation of peripheral 5-HT2 receptors stimulates the secretion of renin, while activation of peripheral 5-HT3 receptors increases plasma levels of prolactin but not renin. In humans, the effect of 5-HT-releasing drugs and 5-HT agonists on plasma prolactin concentrations has been studied to a greater extent than effects on most other hormones. In contrast, the renin response to 5-HT agonists and 5-HT releasers has not been well characterized in humans. Because of the important role of the renin-angiotensin system in cardiovascular regulation, studies on the serotonergic regulation of renin release in humans could increase our understanding of cardiovascular disorders associated with altered serotonergic function. Examples include anxiety and consequences of cocaine abuse. In conclusion, comparing the serotonergic regulation of prolactin and renin secretion indicates similarities that might shed light on common brain mechanisms that regulate neuroendocrine function.
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PMID:Serotonergic regulation of renin and prolactin secretion. 878 3

To test the hypothesis that the mechanisms of 5-HT1 and 5-HT2 receptor-mediated hormonal responses are different, we compared the effects of hypothalamic paraventricular nucleus (PVN) lesions on the ACTH/corticosterone, prolactin and oxytocin responses to the 5-HT1A agonist ipsapirone (1 and 2 mg/kg), the 5-HT2C agonist m-chlorophenylpiperazine (m-CPP, 0.6 mg/kg), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg) in chronically cannulated, freely moving male rats. Pharmacological characterization using antagonists with different affinity for 5-HT2A and 5-HT2C receptors revealed that DOI's responses were mediated mainly by 5-HT2A receptors and m-CPP's responses were almost exclusively mediated by 5-HT2C receptors. ACTH/corticosterone responses to ipsapirone, DOI and m-CPP were almost completely blocked after PVN lesions. Prolactin responses were significantly different in lesioned rats only after DOI and m-CPP challenges. Oxytocin responses to ipsapirone and DOI, but not m-CPP were markedly attenuated after PVN lesions. The present findings suggest that the PVN, or neural pathways close to it, mediate corticosterone and in some cases prolactin and oxytocin responses to selective stimulation of 5-HT1A, 5-HT2A, or 5-HT2C receptors.
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PMID:Role of the hypothalamic paraventricular nucleus in 5-HT1A, 5-HT2A and 5-HT2C receptor-mediated oxytocin, prolactin and ACTH/corticosterone responses. 878 18

The purpose of the present paper was to investigate the relationship of the serotonergic and dopaminergic systems to subscales of sensation seeking (SS). Two of the subscales, Disinhibition (DIS) and Experience Seeking (ES), were chosen for analysis based on their representation of the two major factors obtained in a factor analysis: DIS represents a factor of lack of impulse control and ES a factor of novelty seeking. In studies 1 and 2 responsivity to a serotonergic (5-HT) challenge by a 5-HT1a receptor agonist (ipsapirone) was investigated by drug-induced prolactin (PRL) and cortisol responses, as well as by emotional states and behavioral measures. The dopaminergic (DA) response to a DA agonist (lisuride) and antagonist (fluphenazine) was analyzed in a condition of smoking deprivation (study 3) using PRL responses, emotional states, and behavioral measures of nicotine craving as dependent variables. In the studies of the serotonergic system, high ES subjects showed a blunted cortisol response in both studies and high DIS subjects demonstrated a blunted PRL response in study 2. A frequently observed side effect of serotonergic agonists, increase in emotional arousal, was not observable with ipsapirone in high ES and high DIS subjects as compared to low scorers. Behavioral aggression, which had been experimentally induced in study 2, was increased in high ES as well as in high DIS by the 5-HT1a agonist which exerted antiaggressive effects in low scorers. These findings were found compatible with the idea of a generally low responsivity of the serotonergic system in high ES as well as in high DIS types of sensation seekers of 5-HT1a subsensitivity in high DIS and subsensitivity of other postsynaptic 5-HT receptors in high ES. There was no association between SS subscales and DA-induced decrease of PRL, but high ES subjects seemed to tolerate nicotine deprivation better than low ES subjects indicating that they were less susceptible to deprivation of nicotine-induced DA. But craving for nicotine was increased in high ES subjects by the DA agonist lisuride as opposed to the antagonist, which was taken as evidence that DA stimulation may induce approach behavior in high ES. Although only two subscales had been selected for the investigation, this approach suggests both common and different relationships between SS subscales and neurotransmitter systems.
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PMID:Serotonin and dopamine as mediators of sensation seeking behavior. 891 73

We studied the endocrine and subjective responses that followed acute administration of the 5-HT1A receptor agonist buspirone (0.5 mg/kg orally) in 11 male patients with chronic fatigue syndrome (CFS) and a group of matched healthy controls. Patients with CFS had significantly higher plasma prolactin concentrations and experienced more nausea in response to buspirone than did controls. However, the growth hormone response to buspirone did not distinguish CFS patients from controls. Our data question whether the enhancement of buspirone-induced prolactin release in CFS is a consequence of increased sensitivity of post-synaptic 5-HT1A receptors. It is possible that the increased prolactin response to buspirone in CFS could reflect changes in dopamine function.
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PMID:Increased prolactin response to buspirone in chronic fatigue syndrome. 893 8

We studied the effect of 3 weeks treatment with the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, on hormonal and psychological responses to buspirone, a 5-HT1A receptor partial agonist which also binds to dopamine receptors, in normal male volunteers. Eleven subjects received buspirone, 30 mg, and placebo before, and in week 3 of fluvoxamine treatment (mean dose 127 mg/day). Placebo and buspirone were given in a balanced order, double-blind. Buspirone significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations but had no significant effect on cortisol (CORT) or temperature. Significant psychological effects of lightheadedness, tiredness and difficulty thinking occurred. Fluvoxamine treatment resulted in a nearly 3-fold increase in plasma buspirone with a similar enhancement of the PRL response. In contrast the GH and psychological responses were blunted. The increased buspirone concentrations are likely to be due to inhibition of first pass liver metabolism by fluvoxamine acting on the cytochrome P-450 system. The PRL response is probably mediated by antagonism of pituitary dopamine-D2 receptors and its enhancement by fluvoxamine treatment may be a pharmacokinetic effect. The blunting of GH and psychological responses suggest that 5-HT1A receptor function is reduced by chronic fluvoxamine treatment.
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PMID:The effect of chronic fluvoxamine on hormonal and psychological responses to buspirone in normal volunteers. 894 9

To determine whether emotional stress-induced rises in stress hormone levels are mediated by activation of 5-HT1A receptors, we studied the effects of the selective 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) on plasma ACTH, corticosterone, prolactin, and glucose levels in the conditioned ultrasonic vocalisation (USV) model in adult rats. The effects of WAY-100635 on USVs were also investigated in this paradigm. WAY-100635 (0.3, 1, and 3 mg/kg SC) had no clear effects on basal plasma ACTH, corticosterone, and glucose levels, but the 3 mg/kg dose significantly increased the plasma prolactin levels. The increases in plasma ACTH, corticosterone, and prolactin levels induced by the USV procedure were not affected by WAY-100635. This indicates that the 5-HT1A receptor does not play a major role in the distress-induced activation of the hypothalamic-pituitary-adrenal axis and prolactin secretion. The USVs were significantly enhanced by low doses of WAY-100635 (0.03 and 0.3 mg/kg SC), whereas higher doses (1.0 and 3.0 mg/kg SC) had no effect. These findings suggest that blockade of 5-HT1A receptors during stress may enhance the behavioural stress-response.
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PMID:The 5-HT1A receptor is not involved in emotional stress-induced rises in stress hormones. 895 69


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