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

We recently reported that chronic administration of the 5-HT1A receptor agonist, ipsapirone (0.5 milligrams in drinking water for 3 weeks), has anxiolytic activity in the rat. Herein, we investigated whether this treatment promotes tachyphylaxis to the acute neuroendocrine effects of ipsapirone. Rats chronically treated with ipsapirone displayed a 7% decrease in body weights, compared to vehicle-pretreated rats, thereby confirming previous observations. On the other hand, ipsapirone pretreatment did not affect basal plasma levels of adrenocorticotropin (ACTH), corticosterone, prolactin, aldosterone, and renin activity, nor did it affect their respective rises following an acute ipsapirone (50 mg/kg PO) challenge. Moreover, ipsapirone pretreatment did not affect the increase in plasma prolactin levels elicited by the dopaminergic receptor antagonist haloperidol. These results suggest that neither the 5-HT1A receptors nor the catecholamine receptors that mediate ipsapirone acute neuroendocrine effects develop tolerance to stimulation upon sustained ipsapirone treatment.
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PMID:Chronic treatment with an anxiolytic dose of the 5-HT1A agonist ipsapirone does not alter ipsapirone acute neuroendocrine effects. 790 66

The partial DA receptor agonist preclamol, (-)-3-PPP (50-200 mumol/kg, s.c.) partially reversed the catalepsy induced by the dopamine (DA) receptor antagonists haloperidol (5.3 mumol/kg, i.p.) and raclopride (20.1 mumol/kg, i.p.) in rats. Terguride (transdihydrolisuride), a partial DA receptor agonist with an efficacy lower than that of preclamol, blocked haloperidol (10.6 mumol/kg, i.p.) induced catalepsy at 5 mumol/kg, s.c., but not at 20 mumol/kg, s.c. The effects of terguride in this assay are possibly related to the compound's mixed partial DA agonist/5-HT1A receptor agonist properties. The high efficacy agonist, pramipexole (SND 919) also blocked haloperidol induced catalepsy at 50 mumol/kg, s.c. Haloperidol (0.33-1.3 mumol/kg, i.p.) reduced the locomotor activity down to 5% of saline controls and elevated limbic and striatal DOPA accumulation. When combined with haloperidol, preclamol (100-200 mumol/kg, s.c.) antagonized both the strong hypomotility and increase in DOPA accumulation. Finally, the elevation of serum prolactin in rats induced by haloperidol (0.25 mumol/kg, i.p.) was significantly antagonized by co-administration of preclamol (39 mumol/kg, s.c.). These results show that partial DA agonists can reverse both behavioral, biochemical and neuroendocrine effects of neuroleptics. It also suggests the utility of partial DA receptor agonists in combination with classical neuroleptics in order to minimize the appearance of extrapyramidal side-effects and hyperprolactinemia.
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PMID:Partial dopamine receptor agonists reverse behavioral, biochemical and neuroendocrine effects of neuroleptics in the rat: potential treatment of extrapyramidal side effects. 790 92

Previous studies have suggested that chronic cocaine administration may affect serotonergic function and that serotonin (5-HT) may be of importance in cocaine craving. Ten male cocaine addicts and 28 male normal controls were challenged with MK-212 (6-chlor-2-[1-piperazinyl]-pyrazine) (20 mg), a direct acting 5-HT receptor agonist which has affinity for a variety of 5-HT receptor subtypes, and placebo, on separate days. The plasma cortisol and prolactin (PRL) concentrations and oral body temperature responses to MK-212 and placebo were compared between groups. The temperature response to MK-212 was significantly blunted in cocaine addicts compared to normal controls. However, the plasma cortisol and PRL responses to MK-212 did not differ between the two groups. These results suggest selective alteration of presynaptic 5-HT1A or postsynaptic 5-HT2A/2C function in cocaine addicts.
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PMID:Blunted oral body temperature response to MK-212 in cocaine addicts. 795 51

The phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced dose-related increases in plasma concentrations of prolactin, adrenocorticotropic hormone (ACTH) and corticosterone but not growth hormone in rats. Pretreatment with metergoline (serotonin, 5-HT1/5-HT2 antagonist), ritanserin and mianserin (5-HT2A/5-HT2C antagonists) significantly attenuated DOM-induced increases in prolactin, ACTH and corticosterone, whereas mesulergine (5-HT2A/5-HT2C antagonist) pretreatment significantly attenuated DOM-induced increases in plasma prolactin and ACTH but not corticosterone. Pretreatment with propranolol (beta adrenoceptor antagonist that also has high binding affinity for 5-HT1A, 5-HT1B and 5-HT2C sites), MDL-72222 and ondansetron (5-HT3 antagonists) attenuated DOM's effect on plasma prolactin, but did not attenuate DOM-induced increases in either ACTH or corticosterone. On the other hand, spiperone (5-HT1A/5-HT2A/D2 antagonist) pretreatment significantly attenuated DOM-induced increases in ACTH but not corticosterone. These findings demonstrate involvement of 5-HT2A/5-HT2C and 5-HT3 receptors in mediating DOM-induced increases in plasma prolactin, whereas DOM-induced increases in ACTH appear to be mediated by stimulation of 5-HT2A receptors. DOM-induced corticosterone secretion appears to be mediated by stimulation of 5-HT2A and/or 5-HT2C receptors. DOM does not affect growth hormone secretion in rats.
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PMID:Role of various 5-HT receptor subtypes in mediating neuroendocrine effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats. 796 7

The influence of cocaine exposure on serotonergic neurons and postsynaptic 5-HT1A receptor-mediated responses was evaluated by measuring neuroendocrine responses to a serotonin (5-HT) releaser or a 5-HT1A agonist. Male rats received cocaine (15 mg/kg, i.p.) or saline twice daily for 7 days. Forty-two hr after the final cocaine injection, the 5-HT releaser d-fenfluramine (0, 0.2, 0.6, 2, or 5 mg/kg, i.p.) or the 5-HT1A agonist, 8-OH-DPAT (0, 10, 50, 200 or 500 micrograms/kg, s.c.) were administered. Blood samples were then collected for analysis of plasma ACTH, prolactin, and renin concentrations. The ACTH responses to d-fenfluramine and 8-OH-DPAT were inhibited in cocaine pretreated rats. However, the prolactin responses to d-fenfluramine and 8-OH-DPAT were not significantly modified by cocaine exposure. Additionally, the renin response to d-fenfluramine was unaltered by repeated cocaine administration, while 8-OH-DPAT did not alter renin secretion in either pretreatment group. In contrast to published reports which show that cocaine exposure produces supersensitive 5-HT2A and/or 5-HT2C receptor-mediated responses, the present data suggest that repeated cocaine exposure produces subsensitivity to at least some postsynaptic 5-HT1A receptors. Cocaine-induced deficits in the ACTH response to 5-HT releasers may reflect 5-HT1A receptor subsensitivity, but presynaptic deficits cannot be excluded. Examination of the ACTH response to 5-HT1A agonists may represent a valuable approach to determine deficits in 5-HT function in human cocaine abusers.
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PMID:Repeated cocaine exposure inhibits the adrenocorticotropic hormone response to the serotonin releaser d-fenfluramine and the 5-HT1A agonist, 8-OH-DPAT. 798 71

The present study had two objectives: (1) to provide information on neuroendocrine challenge tests that can lead to diagnostic tests in humans; and (2) to confirm our previous observation that chronic fluoxetine selectively inhibits serotonin (5-HT1A) receptor function. We determined the effect of chronic fluoxetine and desipramine (DMI) on the hormone response to ipsapirone, a 5-HT1A agonist and a potential anxiolytic drug. Ipsapirone increased oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, and prolactin, but not renin or vasopressin concentrations in plasma. Chronic fluoxetine, but not DMI, significantly inhibited the effect of ipsapirone on plasma oxytocin, ACTH and corticosterone concentrations. Chronic fluoxetine also reduced the Bmax for 3H-8-hydroxy-2-(dipropylamino) tetralin (3H-8-OH-DPAT) labelled 5-HT1A receptors in the midbrain. Neither antidepressant altered the density or affinity of 5-HT uptake sites. In conclusion, the present results confirm our previous results using 8-OH-DPAT as a challenge, and suggest that chronic 5-HT uptake inhibition results in adaptive changes leading to decreased function of the 5-HT1A receptor system. Finally, because ipsapirone may be administered to humans, it might be usable to evaluate 5-HT1A receptor function in depressed patients.
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PMID:Attenuation of hormone responses to the 5-HT1A agonist ipsapirone by long-term treatment with fluoxetine, but not desipramine, in male rats. 799 56

Treatment of rats with the serotonin 5-HT1A agonist 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.) markedly elevated plasma levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH) and prolactin (PRL); the levels of growth hormone were unaffected. Pretreatment with the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 6 mg/kg s.c.) greatly attenuated the increase in plasma CORT produced by 8-OH-DPAT (0.3 mg/kg s.c.). Prevention of EEDQ-induced 5-HT1A receptor inactivation by prior treatment with the reversible mixed 5-HT1A/beta-adrenergic antagonist (+/-)pinodolol (30 mg/kg s.c.) blocked the reduction of the CORT response to 8-OH-DPAT. In contrast, prevention of EEDQ-induced inactivation of 5-HT2, alpha-1- and alpha-2-adrenergic and D1 and D2 dopamine receptors by a cocktail of selective antagonists of these receptors did not block the attenuation of the CORT response to 8-OH-DPAT. Dose-response curves were obtained for 8-OH-DPAT (0.01-3 mg/kg s.c.)-induced elevation of plasma CORT, ACTH and PRL after treatment (24 hr earlier) with vehicle or EEDQ (6 mg/kg s.c.) and analyzed for the extent of receptor reserve. Whereas substantial receptor reserves were observed for the 8-OH-DPAT rise in plasma CORT (80%) and ACTH (50%), no receptor reserve was seen for the increase in plasma PRL. The results are discussed with regard to potential differences in the receptors, G proteins, effectors and/or stoichiometric relationships between these components of the signal transduction pathway, leading to elevation of these plasma hormones after treatment with 8-OH-DPAT.
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PMID:Differential receptor reserve for 5-HT1A receptor-mediated regulation of plasma neuroendocrine hormones. 799 33

The cortisol response to ipsapirone (a 5-HT1A-partial agonist that produces a dose-dependent increase in plasma cortisol secretion in man) is blunted in major depression. Buspirone is another 5-HT1A agonist that increases cortisol secretion in man. This study investigated cortisol and prolactin (PRL) responses to buspirone (30 mg orally) in 45 major depressed subjects and 28 normal controls. Buspirone administration yielded a significant increase in cortisol and PRL levels in both normal controls and depressed subjects. No differences in buspirone-induced hormone responses were found either between major depressives and normal controls or between melancholic and nonmelancholic depressives. There were no significant relationships between severity of depression and any of the hormonal responses to buspirone. PRL responses to buspirone were significantly higher in women than in men.
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PMID:Effects of buspirone on plasma prolactin and cortisol levels in major depressed and normal subjects. 801

This study tested whether a new serotonin (5-HT1B) agonist, 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxy-pyrrolo[3,2-b]pyridine (CP-93,129), could be used to study the potential role of 5-HT1B receptors in the secretion of adrenocorticotropic hormone (ACTH), prolactin, and renin. CP-93,129 has a high affinity for 5-HT1B receptors but low affinity for other 5-HT receptor subtypes. In addition, CP-93,129 does not readily cross the blood-brain barrier. The secretion of ACTH, prolactin, and renin is known to be increased after activation of 5-HT receptors. ICV injections of CP-93,129 (100 micrograms/kg) increased the plasma concentrations of ACTH, prolactin, and renin. CP-93,129 also increased blood pressure and reduced heart rate. To determine whether these effects of CP-93,129 are centrally mediated, we compared them with IP injection of the same dose of CP-93,129. IP-injected CP-93,129 did not alter blood pressure or heart rate and did not elevate plasma prolactin and renin concentrations. To determine whether 5-HT1B receptors mediate the central effects of CP-93,129, rats were pretreated with the 5-HT antagonists l-propranolol or metergoline prior to ICV injections of doses of CP-93,129 (0-100 micrograms/kg). The 5-HT1A/1B/2A/2C antagonist metergoline (0.5 mg/kg, IP) failed to inhibit the CP-93,129-induced elevation of ACTH, prolactin, or renin concentrations. In contrast, the 5-HT1A/1B/beta antagonist l-propranolol (20 micrograms/kg, ICV) inhibited the renin but not the ACTH or prolactin responses to ICV CP-93,129.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ICV injection of the serotonin 5-HT1B agonist CP-93,129 increases the secretion of ACTH, prolactin, and renin and increases blood pressure by nonserotonergic mechanisms. 809 Aug 11

Acute stimulation of 5-HT1A receptors has been reported to diminish some 5-HT2 receptor-mediated responses in the rat, but there is controversy as to whether repeated stimulation of 5-HT1A receptors leads to identical changes. In this study, we tested the influence of repeated treatment with the 5-HT1A receptor agonist ipsapirone (0.5 g/l in drinking water for 21 days) on some 5-HT2 receptor-mediated responses elicited by the acute injection of the 5-HT1C/5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). These responses included hyperglycemia, corticosterone release, and head shakes; cortical 5-HT2 receptor number and DOI-induced prolactin release (a 5-HT1C/5-HT2 receptor-mediated event) were also analyzed. In a first series of experiments, ipsapirone administration for 1, 8, 15, and 20 days reduced the duration fo shock-induced ultrasonic vocalization. Ipsapirone administration for 21 days reduced fluid intake and decreased body weight, but did not affect baseline plasma glucose, corticosterone, and prolactin levels or cortical 5-HT2 receptor number. The increases in plasma glucose levels elicited by acute injection of either DOI (0.1-1 mg/kg i.v.) or clonidine (an alpha 2-adrenoceptor agonist; 0.05 mg/kg i.v.) were reduced in ipsapirone-pretreated rats. The maximal effects of DOI and clonidine on plasma corticosterone or prolactin levels were not affected by ipsapirone pretreatment. Ipsapirone decreased the area under the corticosterone curve in both DOI- and clonidine-treated rats. Lastly, the head-shake response to DOI (0.5-2 mg/kg s.c.) was similar in vehicle- and ipsapirone-pretreated rats. These data indicate that a 3-week treatment with anxiolytic doses of the 5-HT1A receptor agonist ipsapirone does not desensitize 5-HT2 receptors.
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PMID:Subchronic treatment with anxiolytic doses of the 5-HT1A receptor agonist ipsapirone does not affect 5-HT2 receptor sensitivity in the rat. 809 65


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