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)

The effects of the relatively specific serotonergic agonists 8-OH-DPAT (5-HT1A), TFMPP (5-HT1B), and DOB (5-HT2) were studied on defensive aggressive behavior in rats using the water competition test, 8-OH-DPAT (up to 0.25 mg/kg) and TFMPP (up to 1 mg/kg) were found to be ineffective, whereas DOB (up to 0.4 mg/kg) significantly reduced aggressive behavior in this test as well as in the offensive aggression test of the resident-intruder model. These results, combined with those from other studies, suggest that stimulation of 5-HT1A, 5-HT1B, and 5-HT2 receptors reduces offensive aggression, whereas defensive aggression is only decreased by 5-HT2 stimulation.
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PMID:Effects of selective serotonergic agonists on aggressive behavior in rats. 761 17

1. We investigated the acute effects of 5-hydroxytryptamine (5-HT), and of the 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), buspirone and SR 57746A, on rat faecal pellet output and water content. 2. 5-HT, 8-OH-DPAT, buspirone and SR 57746A, a new selective 5-HT1A receptor agonist, displaced [3H]-8-OH-DPAT from specific binding sites in rat hippocampus membranes (Ki, nM; 1.8, 1.2, 15, 3.1 respectively) and stimulated rat defaecation dose-dependently. SR 57746A and buspirone induced 1 g dry weight of faeces at 1.3 and 6.1 mg kg-1, p.o. (AD1) respectively. 8-OH-DPAT and 5-HT stimulated defaecation after s.c. injection (AD1, 0.07 and 7.5 mg kg-1, respectively). All these agents increased faecal water content. 3. The putative 5-HT1A receptor antagonist, pindolol, injected s.c. or i.c.v., significantly reduced the defaecation induced by systemically administered 8-OH-DPAT, buspirone or SR 57746A, but not 5-HT. 4. Pretreatment with p-chlorophenylalanine (i.p.) or 5,7-dihydroxytryptamine (i.c.v.), according to protocols designed to cause either generalized or CNS-limited 5-HT depletion respectively, also reduced the defaecation induced by buspirone or SR 57746A. 5. No specific 5-HT1A binding sites could be labelled by incubating rat colon membranes with [3H]-8-OH-DPAT, and in vitro preparations of rat colon segments showed no response to 8-OH-DPAT or SR 57746A up to 5 microM. 6. After eight days' repeated daily treatment, complete tolerance developed to the stimulant effects of SR 57746A and buspirone on faecal water content, but not on faecal pellet output. This suggests that faecal mass excretion and water exchange through the gut wall are affected by independent mechanisms.7. The present findings support the involvement of central 5-HTIA receptors in intestinal propulsion and regulation of luminal fluid content, presumably accounting for the drug-induced defaecation in rats.
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PMID:Drug-induced defaecation in rats: role of central 5-HT1A receptors. 764 78

The effect of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on spatial and non-spatial learning in a water maze was studied using two tasks of equal difficulty, with the same motor, motivational and reinforcement demands. Rats were examined for choice accuracy in a two-platform spatial discrimination task. Rats treated subcutaneously with 100 micrograms/kg 8-OH-DPAT were impaired in choice accuracy with no effect on latency. Treated rats made more errors of omission than controls only on days 1 and 2 of training. Infusion of 1 microgram/microliter spiroxatrine (SPX) or 5 micrograms/microliters of (+)WAY100135, two potent 5-HT1A receptor antagonists, in the CA1 region of the dorsal hippocampus antagonized the impairment in choice accuracy caused by 8-OH-DPAT. The effect on errors of omission on days 1 and 2 of training were not significantly modified by spiroxatrine or (+)WAY100135. Rats treated with 8-OH-DPAT were not impaired in their ability to learn a visual discrimination in a water maze. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus impairs spatial but not visual discrimination in rats.
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PMID:8-OH-DPAT impairs spatial but not visual learning in a water maze by stimulating 5-HT1A receptors in the hippocampus. 774 2

The present study investigates the comparative repopulation kinetics of 5-hydroxytryptamine (5-HT)1A, 5-HT1B, and 5-HT2A receptors in rat cortex homogenates after irreversible receptor inactivation by N-ethoxycarbonyl-1,2-ethoxydihydroquinoline. Adult male rats were administered a single subcutaneous dose of vehicle (1:1 ethanol/water) or N-ethoxycarbonyl-1,2-ethoxydihydroquinoline (10 mg/kg), and the recovery of 5-HT receptor subtypes was measured at various times after injection (4-336 hr). Despite comparable control Bmax values for 5-HT1A (84 +/- 2 fmol/mg of protein) and 5-HT1B (94 +/- 4 fmol/mg) subtypes, marked differences were noted in their 1) receptor production rates (r = 0.349 versus 0.235 fmol/mg of protein/hr), 2) receptor degradation rate constants (k = 0.0056 versus 0.0033 hr-1), and 3) half-lives of receptor recovery (124.1 versus 212.5 hr). For 5-HT2A receptors, both r and k for agonist [(+/-)-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane]- or antagonist ([3H]ketanserin)-labeled sites were markedly greater than the respective values for the 5-HT1 subtypes. In addition, the significantly different Bmax values for agonist- versus antagonist-labeled 5-HT2A receptors (79 +/- 4 versus 206 +/- 10 fmol/mg) were reflected exclusively as a 2.6-fold difference in receptor production rates, because degradation rate constants (k) were identical. Moreover, the stoichiometry of agonist-labeled to antagonist-labeled 5-HT2A receptors was not altered at any time point during recovery. These data indicate that 1) comparable receptor steady state Bmax values for 5-HT receptor subtypes may be due to markedly different receptor kinetic parameters (r and k), 2) differences in r and k are greater between 5-HT receptor families (i.e., 5-HT1 versus 5-HT2) than among subtypes within a family (i.e., 5-HT1A versus 5-HT1B), and, 3) despite marked changes in 5-HT2A receptor density, the percentage of receptors in the agonist-labeled, high affinity state is maintained.
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PMID:Comparative recovery kinetics of 5-hydroxytryptamine 1A, 1B, and 2A receptor subtypes in rat cortex after receptor inactivation: evidence for differences in receptor production and degradation. 780 31

The effect of the azapirone derivative ipsapirone on anxiety and the free-choice consumption of alcohol was studied in male rats. Animals were housed three in a cage with a different composition each day to increase anxiety. The animals were offered a two-bottle free choice consumption of tap water or a 5% ethanol solution. Ipsapirone was given in the drinking fluid daily at about 10 mg/kg per day. As expected, social unstable groups exhibited a higher level of anxiety as compared to social stable groups. Ipsapirone reduced significantly the anxiety in the unstable group. Pretreatment with ipsapirone before alcohol exposure resulted in a marked decrease of subsequent ethanol intake by about 45% as compared to drug free control animals. Administration of the drug to rats already drinking alcohol showed a similar decrease of ethanol intake by about 50%. These results indicate that the relatively specific 5-HT1A receptor agonist ipsapirone, given orally, reduces anxiety as well as alcohol initiation or maintenance in rats.
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PMID:Influence of the 5-HT1A receptor agonist ipsapirone on voluntary alcohol intake in rats. 781

The selective serotonin(5-HT)1A receptor agonists 8-OH-DPAT and ipsapirone were tested in selectively inbred Wistar rats, with high preference [70-90%: defined as the ratio of ethanol (EtOH) to total fluid intake] for EtOH (10% v/v) over water in a two-bottle free choice situation. Rats were injected shortly before the overnight test session (8:00 P.M.-8:00 A.M.). EtOH and water consumption were determined in 20-min intervals; food consumption after the session. 8-OH-DPAT (ED50: 2.4 mg/kg, SC) and ipsapirone (ED50: 12.5 mg/kg, SC) reduced EtOH preference in a dose-dependent manner. In addition, 8-OH-DPAT increased total fluid intake, whereas ipsapirone enhanced total food intake. The EtOH preference reduction was time-dependent and reached a maximum within the second 4 h after application of 8-OH-DPAT (-73%) and ipsapirone (-72%). The preference reducing effect of ipsapirone (20 mg/kg, PO) was completely blocked by the nonselective 5-HT1A antagonist spiperone (0.05 mg/kg, SC). Local application of 8-OH-DPAT (10 micrograms, 0.5 microliters) into the dorsal raphe nucleus (DRN, a brain area rich in somatodendritic 5-HT1A autoreceptors), reduced the EtOH preference significantly as compared to the saline injection in the same animal (-12%, 8:00-12:00 P.M.). Only marginal effects on ingestion behavior were observed after microinjection into the nucleus accumbens. Reduction of brain 5-HT levels by pretreatment with the 5-HT synthesis inhibitor pCPA (2 x 150 mg/kg, IP) resulted in a short lasting, marked reduction (-54%) and a long lasting, small attenuation of the EtOH preference. Total food consumption was strongly decreased but returned soon to normal; total fluid intake was only slightly decreased. The EtOH preference reducing effect of ipsapirone (5 and 20 mg/kg, SC) was attenuated in pCPA-pretreated rats. The present data suggest that 5-HT1A receptor ligands reduce EtOH preference via stimulation of 5-HT1A receptors in the DRN. The possibility of additional mechanism(s) is discussed.
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PMID:Ipsapirone and 8-OH-DPAT reduce ethanol preference in rats: involvement of presynaptic 5-HT1A receptors. 787 Sep 97

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

An involvement of serotonergic innervation of the hippocampus (HP) and the nucleus accumbens septi (NAS) in anxiolytic activity of benzodiazepine midazolam and 5-HT1A receptor agonists was studied in two different animal models of anxiety. Injection of midazolam (10.0 and 20.0 micrograms) or 8-OH-DPAT (0.5 and 1.0 micrograms) into the hippocampus increased punished consumption of water in the Vogel conflict test. Buspirone given at 0.1, 0.5 and 1.0 microgram was ineffective in the Vogel test, while at 5.0 micrograms it enhanced shock-induced suppression of drinking. In the open-field test midazolam (0.01 and 0.1 microgram), 8-OH-DPAT (0.1, 0.5 and 1.0 microgram) and buspirone (2.5 and 5.0 micrograms) increased the number of entries into the central part of the open-field and the time spent in the central sector. Depletion of 5-HT had no influence on the anxiolytic-like effect in the open-field test of intrahippocampally-administered 8-OH-DPAT (0.5 microgram), but the drug tended to increase motor activity in lesioned animals. Midazolam and buspirone injected into the NAS did not have an anxiolytic effect in the Vogel test. A small increase in punished drinking was observed after 8-OH-DPAT (1.0 and 2.5 micrograms). Following intra-NAS injection, midazolam, 8-OH-DPAT and buspirone all failed to produce any marked anxiolytic-like effect in the open-field test. It appears that the hippocampus, rather than the NAS, is involved in mediating anxiolytic-like effects of 5-HT1A receptor agonists. Hippocampal postsynaptic 5-HT1A receptors may account for the anti-emotional influence of this group of drugs. The results indicate some similarities in the psychotropic profile of 5-HT1A receptor agonists and midazolam.
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PMID:Serotonergic innervation of the hippocampus and nucleus accumbens septi and the anxiolytic-like action of midazolam and 5-HT1A receptor agonists. 790 94

The affective mimetic responses of male Wistar rats with prior access to 6% ethanol in their home cages were observed during intraoral infusions of an equivalent alcohol solution. Ethanol preference in the home cage appeared unrelated to measures of aversion and ingestion in the taste reactivity tests in normal rats. Adrenalectomy, which significantly reduced home cage ethanol preference, failed to influence the taste reactions elicited by ethanol or water. On the other hand, treatment of intact rats with the 5-HT1A receptor agonist ipsapirone (2.5 mg/kg), a drug that also decreases ethanol drinking in two-bottle intake tests, did increase the duration of aversive groomings, whereas measures of ingestion remained unaffected. These results suggest that ipsapirone, but not adrenalectomy, may alter the palatability of ethanol; this perceptual change may partly underlie the ability of ipsapirone to reduce home cage alcohol drinking in the rat.
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PMID:Taste reactivity to ethanol in rats: influence of adrenalectomy or ipsapirone. 794 82

The interaction between serotonin (5-HT)1A and nicotinic cholinergic receptors in the regulation of spatial navigation behavior in the Morris water maze (WM) test was studied. Pretraining intraperitoneal (i.p.) injections of a combination of subthreshold doses of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (a 5-HT1A receptor agonist) at 30 micrograms/kg and mecamylamine (a nicotinic cholinergic receptor antagonist) a 2500 micrograms/kg greatly impaired WM navigation to a hidden platform and slightly, but not statistically significantly, impaired WM navigation to a visible platform. Post-training i.p. injections of this combination had no effect on WM navigation performance. Serotonin depletion induced by p-chlorophenylalanine (PCPA) increased the performance impairing action of pretraining injected combination of 8-OH-DPAT 30 micrograms/kg and mecamylamine 2500 micrograms/kg. In trained rats combined injections of 8-OH-DPAT 30 micrograms/kg and mecamylamine 2500 micrograms/kg given pretraining had no effect on the navigation to a hidden platform located in a familiar or in a novel position. Pretraining trial injected combination of hexamethonium 2000 micrograms/kg (a peripherally acting nicotinic antagonist) and 8-OH-DPAT 30 micrograms/kg had no effect on navigation. These data suggest that a combined treatment with a 5-HT1a receptor agonist and a nicotinic cholinergic receptor antagonist more severely impair non-mnemonic acquisition performance processes than consolidation and retrieval processes.
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PMID:Interaction between 5-HT1A and nicotinic cholinergic receptors in the regulation of water maze navigation behavior. 795 29


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