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

Pindolol has been shown to be a partial agonist at 5-HT1A receptors in preclinical studies. It has also been reported to inhibit the effects of other 5-HT1A partial agonists such as ipsapirone and buspirone on hormone secretion and body temperature in man, indicating its antagonist action at 5-HT1A receptors in man. To determine if pindolol has 5-HT1A agonist as well as antagonist effects in man, pindolol, 30 mg, p.o. and placebo, were given single blind in random order to 23 normal men with indwelling venous catheters and its effects on hormone secretion and body temperature noted. Pindolol significantly increased basal plasma cortisol concentrations, whereas it decreased plasma prolactin (PRL) concentrations and body temperature. The increase in plasma cortisol due to pindolol suggests a 5-HT1A agonist action and is consistent with a 5-HT1A partial agonist mechanism in man whereas the PRL effects are consistent with an antagonist action at 5-HT1A receptors. The effects of pindolol on plasma cortisol concentration and body temperature were significantly negatively correlated. Furthermore, these results indicate significant differences in the 5-HT1A-dependent regulation of PRL and the hypothalamo-pituitary-adrenal (HPA) axis and body temperature, and suggest that human basal PRL secretion is tonically stimulated by 5-HT1A mechanism whereas the HPA axis and body temperature are not. Since rodent studies suggest differences in 5-HT1A receptor sensitivity between males and females, the results reported here need to be replicated in females. These differences in the effect of pindolol are discussed in terms of receptor reserve theory.
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PMID:Effect of pindolol on hormone secretion and body temperature: partial agonist effects. 902 79

To determine whether alterations in 5-HT1A receptor mediated responses induced by a single injection with a selective 5-HT1A receptor agonist is a transient effect, or whether the (de)sensitisation is more persistent, rats were pretreated with the selective and full 5-HT1A receptor agonist, flesinoxan (3 mg/kg SC once daily) for either 1 day or 1 week. Twenty-four hour after the last pretreatment injection, rats were challenged with flesinoxan (3 mg/kg SC), and the effects on plasma corticosterone and prolactin levels, lower lip retraction and behaviour in the shock-probe burying test were determined. Several 5-HT1A receptor mediated responses were modified differentially following the flesinoxan pretreatment. However, all changes induced by a single flesinoxan injection remained present upon repeated flesinoxan administration. The differential changes in the responses to flesinoxan cannot easily be explained by differences in pre- or postsynaptically 5-HT1A mediated responses. The prolactin response to flesinoxan, which is thought to be mediated postsynaptically, was enhanced, whereas the corticosterone response to flesinoxan, which is also mediated postsynaptically, was attenuated. The presynaptically mediated lower lip retraction response was attenuated as well, whereas the behavioural effects of flesinoxan remained relatively unaffected following repeated flesinoxan administration. Upon prolonged flesinoxan pretreatment, the changes induced by a single flesinoxan injection remained present or increased further. Although repeated flesinoxan administration (1 day and 1 week) resulted in 20% lower plasma flesinoxan concentrations, this effect could not explain the neuroendocrine and behavioural findings.
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PMID:Flesinoxan pretreatment differentially affects corticosterone, prolactin and behavioural responses to a flesinoxan challenge. 918 41

As noted previously, it is likely that the tendency to lash out verbally or physically at others is influenced by an interaction among multiple complex biologic factors. We need to investigate how these systems interact with each other to develop a more thorough understanding of the brain's influence over aggressive behavior. We are at a very early stage in our understanding of the neurobiology of aggression. There are no simple tools for studying the complex neurophysiology of the human brain. The studies cited in this article include techniques limited in their utility. As our technologies improve, discovering a more thorough picture of the brain's influence over aggressive behavior may be possible. For example, functional neuroimaging may help to localize abnormal neurotransmitter functioning in the brains of individuals with impulsive aggressive behavior. Our technologies are beginning to reveal the differential effects of subsystems of neurotransmitter regulation. Subtypes of serotonin receptors may differentially mediate impulsive aggressive behaviors. Animal studies suggest that 5-HT 1A receptor stimulation results in a decrease in aggressive behavior. As noted previously, aggressive personality-disordered patients show a blunted prolactin response to the 5-HT1A agonist buspirone. Antagonism of 5-HT 2 receptors appears to decrease aggression, and this effect may explain the ability of newer antipsychotic agents (which, unlike older antipsychotic medications, block 5-HT 2 receptors) to produce a dramatic reduction in aggression and agitation independent of effects on psychotic symptoms. Neglecting psychosocial factors in the causes of aggressive behavior would also be naive. Although environmental factors account for much of the predisposition to aggression, there have been few systematic studies to explore the relationship between life experiences and aggression. In addition, there have been no well-designed studies of the interaction between biology and an individual's environment in the genesis of aggressive behavior. There is some evidence of an association between childhood abuse and neglect and adult antisocial personality disorder, but this relationship might be merely an artifact of the genetic relationship between parental and offspring antisocial personality disorder. As we discussed in the introduction, one of the biggest hurdles in the study of the neurobiology of aggression is the lack of a consensus on definitions. "Intermittent Explosive Disorder" is the only category in DSM-IV that directly addresses individuals with problems with aggression, but the criteria are vague and only focus on a handful of the many patients who exhibit problems with aggressive behavior. It is our hope that investigators in this field can work together toward developing more precise and encompassing diagnostic criteria to study effectively both the neurobiology and treatment of these disorders.
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PMID:The neurobiology of impulsive aggression. 919 21

In the first study the possible role of the hypothalamic paraventricular nucleus (PVN) in 5-HT1A receptor agonist-induced neuroendocrine responses was tested. Surgical lesions of the PVN completely blocked ACTH and corticosterone and markedly attenuated oxytocin but not prolactin responses to ipsapirone, providing evidence for a crucial role of the PVN in these responses. In the second study we have compared the effectiveness of intracerebroventricular and intravenous administration of 8-OH-DPAT in frequently used behavioural models of 5-HT1A receptor activation, namely lower lip retraction, body temperature and tail flick responses. We have found marked differences in the rates of effectiveness. We conclude that these models measure the activation of different subsets with clearly separate location of 5-HT1A receptors.
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PMID:Studies on the sites and mechanisms of 5-HT1A receptor-mediated in vivo actions. 932 12

Neuroendocrine responses to stimulation with a selective serotonin reuptake inhibitor (citalopram) were measured to investigate the effects of all-night sleep deprivation on serotonergic function in healthy male subjects (n = 7). We studied citalopram-stimulated prolactin and cortisol plasma concentrations in a placebo-controlled cross-over protocol following sleep and sleep deprivation. Citalopram infusion (20 mg i.v. at 14:20-14:50 h) after a night of undisturbed sleep prompted robust increases in both plasma prolactin and cortisol concentrations. Following a night of sleep deprivation, by contrast, the citalopram-induced prolactin response was blunted, but the cortisol response was not significantly altered. This differential response pattern relates to the distinct pathways through which serotonin may activate the corticotrophic and the lactotrophic systems. While an unchanged cortisol response does not indicate (but also does not refute the possibility of) an altered serotonergic responsivity following sleep deprivation, the suppressed prolactin response could reflect a downregulation of 5-HT1A or 2 receptors. An alternative, not mutually exclusive, explanation points to the possibility that sleep deprivation activates the tubuloinfundibular dopaminergic system, the final inhibitory pathway of prolactin regulation.
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PMID:Effect of sleep deprivation on neuroendocrine response to a serotonergic probe in healthy male subjects. 936 96

Male subjects exercised at 80% maximal rate of O2 uptake (VO2,max) following oral administration of either placebo or the partial 5-HT1A agonist buspirone (45 mg), using a paired design. Ratings of perceived exertion were higher following buspirone and time to volitional fatigue (median and inter-quartile range) fell significantly by approximately a third from 26 min (24-30 min) on placebo to 16 min (11-19 min) following buspirone. Serum prolactin was significantly elevated following buspirone administration, indicating increased hypothalamic 5-HT1A receptor stimulation. There were no significant differences in blood lactate or serum glucose between the trials. This study supports the possible central modulation of exercise tolerance by serotonergic pathways, although a role for dopamine cannot be excluded.
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PMID:The effects of buspirone on perceived exertion and time to fatigue in man. 941 36

Significant progress has been made in understanding psychosocial, psychological, and environmental factors associated with suicide; however, it is only recently that attention has been paid to the understanding of the neurobiology of suicide. There are several studies that implicate the serotonin (5-HT) system in suicide. Initial evidence was obtained from observations of low 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) of depressed patients with a previous history of suicide attempts. Several strategies have been used to examine the serotonergic system in suicidal behavior, which include the determination of serotonin and its metabolites in CSF and postmortem brain tissues as well as serotonin receptor subtypes in postmortem brain tissues, and in platelets of suicidal patients. The neuroendocrine strategy, often termed the "window to the brain," has been extensively used for studying the serotonergic system in suicide. This chapter will review the results obtained from neuroendocrine and serotonin studies in platelets. Initial studies in platelets focussed on determining serotonin uptake and serotonin transporter binding sites in platelets of depressed and suicidal patients. Whereas several studies have found decreased imipramine binding sites of platelets of depressed patients, imipramine binding sites in platelets of suicidal patients showed inconsistent results. Similarly, no consistent changes in 5-HT uptake have been observed in platelets obtained from suicidal patients compared to nonsuicidal patients. On the other hand, studies of platelet 5-HT2A receptors appear to be quite encouraging. Initially, several investigators indicated that they found an increase in platelet 5-HT2A receptors in depressed patients. Subsequently, it was shown that platelet 5-HT2A receptors in suicidally depressed patients were significantly higher compared to nonsuicidally depressed patients and normal control subjects. It has also been shown that platelet 5-HT2A receptors are increased in suicidal patients independent of diagnosis, similar to platelets. 5-HT2A receptors have also been shown to be increased in the postmortem brain of suicide victims by several investigators, although some investigators do not find such an increase. The neuroendocrine strategy provides an important method for studying serotonin function in the central nervous system of depressed and suicidal patents. Using a serotonergic probe of 5-HT1A receptors, several investigators examined ipsapirone-induced prolactin release in suicidal patients and did not find it different that that of control subjects. On the other hand, fenfluramine, which causes release of serotonin and blocks serotonin uptake, causes a decreased release of prolactin in depressed patients compared to normal control subjects. Furthermore it has been shown by some investigators that fenfluramine-induced prolactin release is also decreased in suicidal patients compared to normal control subjects. In summary, platelet and neuroendocrine studies have provided initial evidence sufficient to suggest serotonergic abnormalities in suicidal patients. Most earlier evidence is based on CSF 5-HIAA studies, but it appears that 5-HT2A receptors in both platelet and postmortem brain samples are increased in suicidal patients. The observation that platelet 5-HT2A receptors are increased in suicidal patients independent of diagnosis provides a very useful potential biological marker for identifying suicidal patients.
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PMID:Altered serotonin function in suicide. Evidence from platelet and neuroendocrine studies. 961 99

Previous studies suggest that the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) increases the secretion of oxytocin, adrenocorticotropic hormone (ACTH), corticosterone and prolactin but not renin. However, the lack of selective 5-HT1A receptor antagonists made it difficult to confirm that 5-HT1A receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT1A receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 microg/kg s.c., increased plasma levels of oxytocin (to 970% above basal levels); ACTH (to 1622% above basal levels), corticosterone (to 458% above basal levels) and prolactin (to 313% above basal levels), but not renin. The lowest dose of WAY-100635 (0.1 mg/kg s.c.) significantly inhibited the 8-OH-DPAT-induced increase in plasma oxytocin but not ACTH or corticosterone levels. At a dose of 1 mg/kg (s.c.), WAY-100635 completely blocked the oxytocin and ACTH responses and maximally inhibited the corticosterone response to 8-OH-DPAT, although corticosterone levels were still above basal. In contrast, the increase in prolactin secretion, induced by 8-OH-DPAT was not inhibited by any dose of WAY-100635. At the highest dose of WAY-100635 (10 mg/kg, s.c.), basal prolactin levels were markedly elevated (1550%) and administration of 8-OH-DPAT significantly elevated plasma renin concentration. Taken together, these data indicate that: (1) 8-OH-DPAT stimulates oxytocin, ACTH, and corticosterone but not prolactin secretion via activation of 5-HT1A receptors and (2) blockade of 5-HT1A receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT1A receptor mechanisms.
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PMID:WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion. 965 68

In the present study, we examined denervation-induced changes in the sensitivity of hypothalamic postsynaptic serotonin1A (5-HT1A) receptor function with respect to changes in the dose-dependent elevation in plasma hormones [adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin, prolactin, renin and vasopressin] by the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT). Rats received intracerebroventricular (i.c.v.) injections of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (0.1% ascorbate in saline) 3 weeks before challenge with increasing doses of 8-OH-DPAT (0, 10, 50 or 200 micrograms/kg s.c.). The effectiveness of 5,7-DHT-induced destruction of serotonergic neurons was confirmed by a 93% reduction in [3H]paroxetine-labeled 5-HT uptake sites in the hypothalamus. No changes in basal levels of ACTH, corticosterone, oxytocin, prolactin, renin and vasopressin were observed in rats that received i.c.v. 5,7-DHT injections. The dose-response curves for 8-OH-DPAT-induced elevations of plasma corticosterone and prolactin levels were shifted to the left in rats treated with 5,7-DHT, whereas no significant difference in the ACTH dose-response curve was observed between rats treated with vehicle and rats treated with 5,7-DHT. In contrast, the maximal oxytocin response to 8-OH-DPAT was attenuated in rats treated with 5,7-DHT. A 5,7-DHT-induced decline in the synthesis of oxytocin could explain this phenomenon. Although 8-OH-DPAT did not increase plasma levels of renin or vasopressin in rats treated with vehicle, 8-OH-DPAT produced an elevation (75%) in plasma renin concentration but not in vasopressin levels in rats that received i.c.v. injections of 5,7-DHT. No change was observed in [3H]8-OH-DPAT labeled 5-HT1A receptors in the hypothalamus. In summary, denervation of hypothalamic serotonergic nerve terminals produces supersensitivity of some neuroendocrine responses to 8-OH-DPAT independent of changes in the density of hypothalamic 5-HT1A receptors.
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PMID:Alterations in 8-hydroxy-2-(dipropylamino)tetralin-induced neuroendocrine responses after 5,7-dihydroxytryptamine-induced denervation of serotonergic neurons. 965 67

In order to evaluate the role of glutamate in prolactin secretion, we examined the effects of N-methyl-D,L-aspartic acid (NMDA) receptor antagonists on serum prolactin levels at both resting and restraint-stress conditions in female rats at estrus. NMDA increased basal serum prolactin levels. Administration of the selective NMDA receptor antagonist, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) (5 and 10 mg/kg i.p.), to rats under resting conditions enhanced basal prolactin levels. A low dose of CGS 19755 (3 mg/kg) was unable to modify the hormone serum level. Under stress conditions the pretreatment with CGS 19755 (3 and 5 mg/kg) prevented the increase in serum prolactin levels. This effect was reversed by NMDA (60 mg/kg s.c.). The NMDA receptor antagonist (5 mg/kg) decreased the median eminence concentration of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), without modifying dopamine content. To examine the probable link between serotonin (5-HT) and glutamate in prolactin release, the 5-HT2A/5-HT2C receptor antagonist, ritanserin, was used. Under resting conditions, a dose of 5 mg/kg s.c. blocked the NMDA-induced prolactin release. In rats submitted to restraint, ritanserin decreased the prolactin response and NMDA was unable to correct the stress serum prolactin levels. The 5-HT1A receptor agonist, 8-hidroxypropyl-amino tetralin (8-OH-DPAT) (3 mg/kg s.c.), increased basal serum prolactin levels and restored serum prolactin in stressed animals pretreated with CGS 19755 (5 mg/kg). The present data strongly suggest that the glutamatergic system participates in the regulation of prolactin secretion. A stimulation tone seems to be exerted via the tuberoinfundibular dopaminergic system, and the prolactin release evoked by restraint apparently involves glutamate/NMDA receptors linked to a serotoninergic pathway.
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PMID:NMDA receptor antagonists block stress-induced prolactin release in female rats at estrus. 969 16


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