Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous electrophysiological studies have demonstrated that nicotine, intravenously administered, excites noradrenergic neurons in the locus coeruleus (LC) indirectly by releasing excitatory amino acids (EAA). In the present study the excitatory action of nicotine was inhibited by treatment with the selective 5-HT re-uptake inhibitor citalopram or the 5-HT1A receptor agonist 8-OH-DPAT. It is proposed that the antagonism between nicotine and citalopram or 8-OH-DPAT reflects an interaction between endogenous EAA, e.g. glutamate, and 5-HT. The results may, on a cellular basis, explain the attributed effectiveness of drugs that facilitate serotonergic neurotransmission in promoting smoking cessation.
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PMID:Citalopram and 8-OH-DPAT attenuate nicotine-induced excitation of central noradrenaline neurons. 138 1

The role of 5-HT (serotonin) in regulating lordosis was investigated by combining peripheral administration of the 5-HT agonists 8-OH-DPAT (8-hydroxy-2-[di-N-propylamino]tetralin) or TFMPP (1-[m-trifluoromethylphenyl]piperazine), with intrahypothalamic application of the 5-HT neurotoxin 5,7-DHT (5,7-dihydroxytryptamine). The 5-HT1A agonist, 8-OH-DPAT, significantly inhibited lordosis in 5,7-DHT-treated and non-treated rats. TFMPP, an agonist at 5-HT1B and 5-HT1C receptors, significantly facilitated lordosis in 5,7-DHT-treated and non-treated rats. Our results show that both inhibitory and facilitatory influences of hypothalamic 5-HT on lordosis, are modulated via postsynaptic receptors.
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PMID:5,7-DHT facilitated lordosis: effects of 5-HT agonists. 139 65

1. The actions of 5-hydroxytryptamine (5-HT) and some 5-HT1A receptor ligands on neurones in the rat dorso-lateral septal nucleus were recorded in vitro by intracellular recording techniques. 2. In the presence of tetrodotoxin (1 microM) to block any indirect effects, bath application of 5-HT (0.3-30 microM) hyperpolarized the neurones in a concentration-dependent manner and reduced membrane resistance. The hyperpolarization did not exhibit desensitization and was sometimes followed by a small depolarization. 3. The 5-HT1A receptor ligands, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and buspirone but not the non-selective 5-HT1 receptor agonist, 1-m-trifluoromethylphenylpiperazine (TFMPP), also hyperpolarized the neurones. 4. 5-HT, 8-OH-DPAT and DP-5-CT appeared to act as full agonists whereas buspirone behaved as a partial agonist. The estimated EC50S were: DP-5-CT 15 nM, 8-OH-DPAT 110 nM, 5-HT 3 microM and buspirone 110 nM. 5. At a concentration of 3 microM, the putative 5-HT1A receptor antagonists, spiperone, methiothepin, NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate), produced a parallel rightward shift in the concentration-response curve to 5-HT with no significant reduction in the maximum response. The estimated pA2 values were: NAN-190 6.79, MDL 73005EF 6.59, spiperone 6.54 and methiothepin 6.17.6. The 5-HT2/5-HTlc receptor antagonist, ketanserin (3 microM) and the 5HT3 receptor antagonist, tropisetron (3 microM) did not antagonize the 5-HT-induced hyperpolarizations; however, ketanserin blocked the depolarization which sometimes followed the hyperpolarization.7. It is concluded that the 5-HT-induced membrane hyperpolarization of rat dorso-lateral septal neurones is mediated by 5-HTA receptors.
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PMID:Actions of 5-hydroxytryptamine and 5-HT1A receptor ligands on rat dorso-lateral septal neurones in vitro. 139 88

The 5-HTergic neurons in the mesencephalic raphe nuclei provide a robust projection to the hypothalamic suprachiasmatic nucleus (SCN), the site of a putative neuronal circadian pacemaker. Although it has been suggested that 5-HT neurons may play a role in the circadian timing system, this role has not yet been specified. Prosser et al. (Brain Res., 534 (1990) 336-339) reported that 1 h treatments with quipazine induce robust phase shifts in vitro, and that this effect depends upon the circadian time of treatment. However, quipazine is a non-specific 5-HT agonist. Besides, it is reported that the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetraline hydrobromide (8-OH-DPAT) affected a circadian rhythm of hamster wheel-running activity. In the present study we investigated whether the 5-HT1A agonist 8-OH-DPAT can reset the phase of the SCN clock when it is isolated in vitro. The present results show that 1 h treatments with 8-OH-DPAT induce robust phase advances in vitro when it was administered during the subjective day. This result suggests that 5HT1A receptor functioning may play a role in modulating the phase of SCN clock, especially during the subjective day.
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PMID:Phase-resetting effect of 8-OH-DPAT, a serotonin1A receptor agonist, on the circadian rhythm of firing rate in the rat suprachiasmatic nuclei in vitro. 139 58

The effects of the 5-HT1A receptor 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) administered i.v. on medullary 5-HT neuronal firing and renal sympathetic nerve activity were determined in spontaneously breathing anaesthetized cats. Low doses of 8-OH-DPAT (1-3 micrograms/kg) caused a similar reduction in 5-HT neuronal firing and renal nerve activity while high doses (10-30 micrograms/kg) completely inhibited neuronal firing but caused only 80% inhibition of renal nerve activity. These data are discussed in relationship to the mechanism of sympatholytic action of 8-OH-DPAT and the serotonergic regulation of sympathetic nerve activity.
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PMID:8-OH-DPAT-induced inhibition of renal sympathetic nerve activity and serotonin neuronal firing. 139 44

Radioligand binding studies were performed in membranes of rabbit whole brain and striatum using the novel iodinated radioligand for 5-hydroxytryptamine 5-HT1B and 5-HT1D sites, Serotonin-5-O-Carboxymethyl-Glycyl[125I]Tyrosinamide ([125I]GTI). [125I]GTI labelled a finite number of high affinity sites in rabbit brain membranes, Bmax = 191 +/- 47 fmol/mg protein, pKD (-log mol/l) = 8.50 +/- 0.13, n = 5. The pharmacological profile of [125I]GTI binding was fully comparable to that reported previously in human and other brain preparations known to possess 5-HT1D sites (using either [3H]5-HT or [125I]GTI) and displayed a characteristic rank order of affinity: 5-carboxamido-tryptamine greater than 5-HT = dihydroergotamine greater than or equal to ergotamine greater than or equal to sumatriptan greater than or equal to CGS 12066 greater than or equal to metergoline greater than yohimbine greater than or equal to methysergide greater than ICYP greater than 8-OH-DPAT greater than or equal to CP 93129 greater than (-)pindolol greater than ketanserin greater than isamoltane greater than mesulergine greater than corynanthine greater than buspirone greater than MDL 72222. Autoradiographic studies were performed on rabbit brain slices using [3H]5-HT in the presence of 100 nmol/l 8-OH-DPAT and mesulergine (in order to mask 5-HT1A and 5-HT1C binding sites) and [125I]CYP (iodocyanopindolol) in the presence of 3 mumol/l isoprenaline and 100 nmol/l 8-OH-DPAT (in order to mask beta adrenoceptor and 5-HT1A binding sites). There was no detectable specific binding of [125I]CYP through the brain, thus excluding the presence of 5-HT1B sites in rabbit brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:"5-HT1R" or 5-HT1D sites? Evidence for 5-HT1D binding sites in rabbit brain. 140 10

Anxiolytic drugs, such as the benzodiazepines and the azapirones (ipsapirone, gepirone, buspirone), are well known to affect states of vigilance and to decrease the firing rate of serotoninergic neurones within the dorsal raphe nucleus in rats. In order to examine whether the newly developed 5-HT3 antagonists with potential anxiolytic properties act through similar mechanisms, the effects of several of such antagonists: MDL 72222, ICS 205-930, ondansetron and/or zacopride on both sleep-wakefulness and the discharge of serotoninergic neurones within the dorsal raphe nucleus were investigated in rats. When tested in a wide range of doses (0.05-10 mg/kg, i.p.), none of these drugs significantly affected the states of vigilance, except ondansetron, at 0.1 mg/kg, which increased paradoxical sleep for the first 2 hr after administration and MDL 72222, at 10 mg/kg, which reduced both paradoxical and slow wave sleep and increased wakefulness for the same initial period after treatment. In vivo, in chloral hydrate anaesthetized rats, as well as in vitro, in slices of brain stem, none of the 5-HT3 antagonists tested affected the firing rate of serotoninergic neurones. Similarly, no change in the electrical activity of serotoninergic neurones could be evoked in vitro by superfusion of the tissue with the 5-HT3 agonists, phenylbiguanide (10 microM) and 2-methyl-5-HT (1 microM). At a larger concentration (10 microM), the latter compound reduced the neuronal discharge probably through the stimulation of somatodendritic 5-HT1A autoreceptors since this effect, as that of ipsapirone, could be prevented by 10 microM l-propranolol. Comparison of these data with those obtained with benzodiazepines and 5-HT1A agonists of the azapirone series, supports the concept that different mechanisms are responsible for the anxiolytic-like properties of 5-HT3 agonists, compared to those of other anxiolytic drugs.
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PMID:Central action of 5-HT3 receptor ligands in the regulation of sleep-wakefulness and raphe neuronal activity in the rat. 140 92

It has previously been shown that the 5-HT1A agonist, 8-OH-DPAT, caused discrete changes in cerebral glucose utilization in the rat, as assessed by quantitative 2-deoxyglucose autoradiography. Here, the effect of the putative 5-HT1A antagonist, BMY 7378, on regional cerebral glucose utilization was examined, when injected alone and in rats treated with 8-OH-DPAT. In control rats, BMY 7378 (5 mg/kg, s.c.) markedly increased glucose utilization in the lateral habenular nucleus and moderately reduced glucose utilization in the hippocampal formation. Pretreatment with BMY 7378 (5 mg/kg) significantly attenuated the reductions in glucose utilization in the hippocampus, entorhinal, piriform and cingulate cortex, induced by 8-OH-DPAT (0.25 mg/kg). The 8-OH-DPAT-induced increase in glucose utilization in the copula pyramis, that is putatively associated with the appearance of the 5-HT behavioural syndrome, was also blocked by BMY 7378, as was the behavioural syndrome. In summary, BMY 7378 produced few of the discrete changes in cerebral glucose utilization that are seen with 8-OH-DPAT. However, many of the changes induced by 8-OH-DPAT were reversed by BMY 7378. These data are consistent with the hypothesis that the effects of 8-OH-DPAT on regional cerebral glucose utilization are mediated by 5-HT1A receptors.
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PMID:The putative 5-HT1A antagonist BMY 7378 blocks 8-OH-DPAT-induced changes in local cerebral glucose utilization in the conscious rat. 140 94

Acute cocaine reduces renin secretion. To determine whether serotonergic neurons mediate this effect, male Sprague-Dawley rats received the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (75 micrograms/side, ICV) 2 weeks prior to cocaine injections (3.75-15 mg/kg, IP). 5-HT lesions attenuated the cocaine-induced reduction of plasma renin concentration (PRC), suggesting a partial 5-HT role. To determine which receptors mediate this response, rats were pretreated with the partial 5-HT1A agonist 8-[2-[4-(2-methoxyphenyl)-l-piperazinyl]ethyl]-8-azaspirol-[4,5]- decane-7,9-dione (BMY 7378) (1 mg/kg, SC), the 5-HT1C/5-HT2 antagonist ritanserin (0.1 mg/kg, SC), or the alpha 2/5-HT1A antagonist yohimbine (1 mg/kg, SC) prior to cocaine. None of the antagonists altered the cocaine-induced suppression of PRC, although BMY 7378 and yohimbine elevated PRC. The data suggest that cocaine's effect is partially mediated by a serotonergic mechanism, but do not support a role for 5-HT1A receptors, 5-HT2/5-HT1C receptors, or alpha 2-adrenoceptors in mediating the suppressive effect of cocaine on renin secretion.
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PMID:Cocaine-induced suppression of renin secretion is partially mediated by serotonergic mechanisms. 140 81

To investigate the dependence of the satiating action of cholecystokinin (CCK) on serotonergic action at central 5-HT receptors, we examined the effect of systemic pretreatment with 8-OH-DPAT (a 5-HT1A agonist that decreases central 5-HT synthesis and release via an action at somatodendritic autoreceptors in the brainstem raphe) on the suppression of food intake induced by systemic administration of cholecystokinin octapeptide (CKK-8). 8-OH-DPAT significantly attenuated the satiating action of CKK-8. This result is consistent with the hypothesis that peripherally acting CCK recruits central serotonergic processes to elicit normal satiety.
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PMID:The 5-HT1A agonist 8-OH-DPAT attenuates the satiating action of cholecystokinin. 140 88


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