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 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

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.
Alcohol
PMID:Taste reactivity to ethanol in rats: influence of adrenalectomy or ipsapirone. 794 82

5,7-Dihydroxytryptamine (5,7-DHT) was administered ICV to Wistar male rats. Lesioned rats displayed higher preference for ETOH than sham-lesioned animals. Among 5,7-DHT-pretreated rats 38% became high-preferring, while only 22% of sham-lesioned rats displayed this behavioural pattern (p < 0.05). Both 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; the agonist of serotonin 5-HT1A receptors) and tropisetron (ICS 205-930, the antagonist of 5-HT3 receptors) reduced ETOH consumption in high-preferring, sham-lesioned rats. However, in 5,7-DHT rats the effect of 8-OH-DPAT was completely abolished, while tropisetron retained its antipreference activity. Therefore, it seems that 5-HT1A autoreceptors are critically involved in 8-OH-DPAT action, while 5-HT3 receptor sites responsible for tropisetron action are located beyond the 5-HT system.
Alcohol
PMID:Alcohol drinking in rats treated with 5,7-dihydroxytryptamine: effect of 8-OH-DPAT and tropisetron (ICS 205-930). 794 81

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.
Drug Alcohol Depend 1994 Jun
PMID:Blunted oral body temperature response to MK-212 in cocaine addicts. 795 51

Low doses of the selective 5-HT1A agonist 8-OH-DPAT increase ethanol intake in a limited access paradigm following peripheral injection. This may be due to a reduction in 5-HT neurotransmission following activation of raphe somatodendritic autoreceptors. In order to test this hypothesis, and to determine the effects of selective reductions in raphe 5-HT activity, experiments examined the effects of injecting 8-OH-DPAT into the dorsal raphe (0, 0.02, 0.1, 1 and 2.5 micrograms) or the median raphe (0, 0.1, 1 and 5 micrograms) in rats trained to drink 12% ethanol for 40 min each day. The effects of the GABAA agonist, muscimol, on ethanol intake were also examined. Ethanol intake was increased at the highest dose of 8-OH-DPAT following injection into either site, with no change in water intake. Thus, the effects of 8-OH-DPAT are selective for ethanol. The selective 5-HT1A antagonist, (+)-WAY100135 (0.3, 1 and 3 mg/kg), blocked the effect of 8-OH-DPAT, showing that activation of 5-HT1A receptors underlies the ethanol drinking induced by 8-OH-DPAT. These results are consistent with the idea that reduced 5-HT function increases ethanol intake. Several behavioral mechanisms for this effect are discussed. Muscimol (50-100 ng) also increased ethanol drinking. Following injection into the median raphe, muscimol also stimulated water intake. These effects are probably due to non-specific behavioural activation induced by this treatment. However, the effect of muscimol in the dorsal raphe was specific for ethanol since water intake was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Median and dorsal raphe injections of the 5-HT1A agonist, 8-OH-DPAT, and the GABAA agonist, muscimol, increase voluntary ethanol intake in Wistar rats. 798 73

Arginine8-vasopressin (AVP) has been shown repeatedly to affect learning and memory and to maintain tolerance to ethanol if the brain serotonin and catecholamine systems are intact. In the present study, 5,7-dihydroxytryptamine (5,7-DHT) was injected intracerebroventricularly to disrupt serotonergic projections from the raphe to the forebrain. This resulted in a marked decrease in 5-hydroxytryptamine (5-HT) immunoreactivity in the terminal areas of the septum and the hippocampus, but not in the serotonin-containing neuronal cell bodies in the raphe nuclei. In control rats, tolerance to the motor-impairing effects of ethanol lasted for only 5 days after the cessation of ethanol treatment but could be maintained indefinitely for as long as AVP was given. In the 5,7-dihydroxytryptamine-lesioned rats, AVP was unable to maintain the tolerance. Continuous intracerebroventricular infusion of 5-HT restored the ability of AVP to maintain ethanol tolerance in the lesioned rats. A selective 5-HT2 agonist (alpha-methylserotonin) was equally effective, and a 5-HT3 receptor agonist (2-methylserotonin) was slightly less effective, but the 5-HT1A agonist dipropylaminotetralin (8-hydroxy-dipropylaminotetralin) was totally ineffective in this respect. The results indicate selective involvement of brain 5-HT2 and possibly 5-HT3 receptors in mediating AVP maintenance of tolerance to ethanol but do not pinpoint their specific loci or roles.
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PMID:Selective involvement of central 5-HT2 receptors in the maintenance of tolerance to ethanol by arginine8-vasopressin. 807 72

The behavioral pharmacology of tandospirone (SM 3997), a novel anxiolytic/antidepressant pyrimidinylpiperazine compound with selective pharmacological effects at the 5-HT1A binding site, was investigated in baboons. Animals administered 50 mg/kg/day i.g. tandospirone, showed few behavioral changes (lip droop, ataxia), which decreased over 2 weeks. Substitution of vehicle for tandospirone after 7 weeks produced time-limited suppression of food intake, suggesting a mild withdrawal syndrome. Under an i.v. self-injection procedure, tandospirone (1.0-32 mg/kg/injection) did not maintain responding greater than vehicle, although cocaine and triazolam did. Under a drug discrimination procedure, tandospirone (1-3.2 mg/kg p.o.; 0.1-32 mg/kg, i.m.) did not occasion drug-appropriate responding in baboons trained to discriminate lorazepam or pentobarbital and buspirone (1-18 mg/kg, p.o.; 0.1-1.0 mg/kg, i.m.) did not occasion drug-appropriate responding in the pentobarbital-training group. Tandospirone's profile of effects differs from those for barbiturates and benzodiazepines and suggests low abuse liability.
Drug Alcohol Depend 1993 May
PMID:Behavioral pharmacology of tandospirone in baboons: chronic administration and withdrawal, self-injection and drug discrimination. 810 30

Animal studies as well as clinical studies have suggested that the brain 5-HT system is important for the regulation of voluntary ethanol intake and preference. Previous studies have suggested that 5-HT1A receptor agonists may reduce ethanol preference in rats. In the present study on mice, the 5-HT1A receptor agonists (8-OH-DPAT), ipsapirone, and buspirone all antagonized the locomotor activity (LMA) stimulatory effect of ethanol (2.5 g/kg). The present results provide further support for the notion that the LMA-increasing effect of ethanol may be homologous to its reinforcing properties and that 5-HT1A receptor agonists may counteract these properties as well.
Alcohol
PMID:5-HT1A receptor agonists reduce ethanol-induced locomotor activity in mice. 820 2

Saturable [3H]8-OHDPAT binding to recognition sites of 5-HT1A receptors was shown to be higher in cortical membranes of alcohol-preferring (P) than in membranes of alcohol-nonpreferring (NP) rats. Neither the P nor the NP lines had been previously exposed to ethanol. The increase in binding was mainly due to 40-56% higher density or maximum of binding sites (Bmax) without significant change in affinity or dissociation constant (Kd) for the radioligand. Although Bmax values were also consistently higher in membranes isolated from other brain areas of P rats, including hypothalamus, striatum, and hippocampus, the differences did not reach statistical significance. Similar to the previously reported lack of difference in [3H]ketanserin binding to 5-HT2 receptors in cortical membranes from P and NP rats, there were also no significant differences in saturable binding of [3H]mesulergine and [3H]LY278584 to recognition sites of 5-HT1C and 5-HT3 receptors, respectively. Thus, an upregulation of 5-HT1A receptors in cerebral cortex and possibly in other brain areas of ethanol-naive P rats appears to have occurred as a consequence of the lower 5-HT innervation in this selected line of rats (13,15,27,28).
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PMID:Greater abundance of serotonin1A receptor in some brain areas of alcohol-preferring (P) rats compared to nonpreferring (NP) rats. 825 9

The present study investigates the inactivation and recovery of brain serotonin (5-HT) recognition sites by EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2,-dihydroquinoline). Adult male Sprague-Dawley rats were given a single s.c. injection of vehicle (1:1 EtOH/H2O) or EEDQ (1-20 mg kg-1) and sacrificed at 4 h and 7 days (10 mg kg-1 dose) post-injection. EEDQ dose-dependently reduced the Bmax of 5-HT1A(3H-DPAT),5-HT1B(125I-CYP),5-HT2(3H-ketanserin) and 5-HT2/1C(125I-DOI) receptors in cortical homogenates. In contrast, EEDQ was without effect on the 5-HT transporter recognition site (3H-paroxetine). No significant changes in affinity were observed for 5-HT1B, 5-HT2 or 5-HT2/1C receptors. The rank order of sensitivity to EEDQ inactivation was: 5-HT1A > 5-HT1B > 5-HT2 approximately 5-HT2/1C >>> 5-HT uptake sites. This study demonstrates: (1) differential EEDQ inactivation and recovery of 5-HT receptors and (2) lack of EEDQ inactivation of the 5-HT transporter.
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PMID:In vivo EEDQ dose-dependently inactivates rat brain 5-HT receptors but not 5-HT uptake sites. 828 Aug 61


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