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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 different housing conditions and ethanol treatment (6 vol % in the drinking water) on the in vitro binding characteristics of striatal dopaminergic D2 ([3H]spiperone), hippocampal serotonergic 5-HT1A ([3H]8-OH-DPAT), and cortical benzodiazepine ([3H]flunitrazepam) receptors have been examined. Social deprivation due to contact caging, short- (1 day) and long-term isolation (5 weeks) yielded a significant decrease of striatal D2 receptor density with the greatest decrease after long-term isolation (-21% Bmax) without changes of Kd in comparison to group animals. The effect of ethanol on striatal D2 receptor density depended on the housing conditions. Whereas ethanol treatment reduced receptor density of group animals (down to 88%), chronic exposure to ethanol under long-term isolation elicited no significant alteration of D2 receptor density compared with group animals. Different housing and ethanol treatment had no effect on 5-HT1A receptor affinity and density. Alterations of benzodiazepine receptor density were not found, but social deprivation as well as ethanol treatment of group animals caused an increased affinity of [3H]flunitrazepam (reduced Kd value). These results indicate that different housing conditions of adult rats evoked significant alterations in D2 and benzodiazepine receptor binding assays, which were modified by ethanol treatment in the case of striatal D2 receptor density.
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PMID:Influences of housing conditions and ethanol intake on binding characteristics of D2, 5-HT1A, and benzodiazepine receptors of rats. 750 70

The serotonin system has long been thought to play a role at several steps in the cycle of alcohol abuse. Initial motivation may be triggered by anxiety, which may exhibit a serotonergic component (5-HT1A receptor). Alcohol can potentiate the opening of 5-HT3 receptor ion channels, and agents which elevate serotonergic tone, including serotonergic agonists, uptake inhibitors and releasers, have shown promise in assisting with recovery from alcoholism. In this review, recent advances in serotonin receptor research are presented, with a special emphasis on the impact and interpretation of molecular biological data. Genetic and pharmacological concepts of receptor subtypes are reviewed and related to a new classification system for the 14 currently recognized subtypes of serotonin receptors. The current and likely future impact on drug design of the molecular approach to serotonin receptors is discussed. Finally, the question of why there are so many serotonin receptor subtypes is examined, along with possible roles of multiple G protein and second messenger pathways, and their effect on conserved domains of these receptor proteins.
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PMID:Molecular pharmacology of serotonin receptors. 751 66

This laboratory previously demonstrated that in utero ethanol exposure markedly impairs the development of the serotonergic system in rat brain. Developmental abnormalities could be detected as early as G15 in the brainstem and G19 in the cortex. Because of the importance of fetal serotonin (5-HT) and 5-HT1A receptors for the normal development of 5-HT containing neurons, we initiated studies to determine whether administration of a 5-HT1A agonist, buspirone, to pregnant rats could overcome the adverse effects of in utero ethanol exposure on the developing serotonergic system in offspring. Female, Sprague-Dawley rats were given daily subcutaneous injections of buspirone (4.5 mg/kg) from gestational day 13 (G13) to G20. 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content were determined in the cortex and cortical regions. These experiments demonstrated that the ethanol-associated abnormalities in the development of the serotonergic system can be partially overcome by in utero exposure to buspirone. Specifically, whereas untreated ethanol rats had a deficiency of 5-HT and/or 5-HIAA in whole cortex on PN5, and in the motor cortex on PN19 and 35, no significant differences were detected in these regions of the age-matched offspring of buspirone-treated, ethanol-fed rats. In contrast, the 5-HT and 5-HIAA deficiency in the somatosensory cortex of 19-day-old offspring of ethanol-fed rats was not corrected by in utero buspirone treatment. These results suggest that the abnormal development of cortical projections of serotonergic neurons may be due in part to the low fetal 5-HT content in ethanol-exposed rats and may potentially be overcome by in utero treatment with a 5-HT1A agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Clin Exp Res 1993 Feb
PMID:Treatment of pregnant alcohol-consuming rats with buspirone: effects on serotonin and 5-hydroxyindoleacetic acid content in offspring. 768 Aug 41

Ethanol naive alcohol preferring rodents have low serotonin transmission. Both pharmacological, biochemical and behavioral studies show that increased serotonin transmission influence reduces ethanol consumption in animals. This paper develops the role of serotonin in different lines of ethanol preferring rats and mice, and shows a regulation of 5-HT1A receptors in alcoholised dependent mice. Different sensitivities to ethanol observed between ethanol-preferring and non-preferring rats or mice seems to be at the root of the maintenance of alcohol intake.
Alcohol Alcohol Suppl 1993
PMID:Serotonin in animal models of alcoholism. 774 3

Variations in serotonin neurotransmission influence alcohol consumption (AC). Levels of 5-HT and metabolites are low in some brain regions of alcohol preferring rats and in CSF of alcoholics. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats. Serotonin uptake inhibitors (SUI; e.g., citalopram, fluoxetine) have been studied extensively in humans. In several double-blind randomized, placebo-controlled clinical trials, SUI have consistently decreased AC by averages of 15% to 20% in nondepressed mildly/moderately dependent alcoholics who received no other treatment. Effects were dose-dependent and not related to side effects (few and mild) or changes in anxiety or depression (not observed). SUI also decreased desire to drink and liking for alcohol, thus suggesting a mechanism for effects. Other drugs acting on the 5-HT system have been tested in humans, but results are difficult to interpret. For example, buspirone, a 5-HT1A receptor partial agonist, reduced anxiety and alcohol craving, but not AC; a 5-HT partial agonist, m-CPP, increased alcohol craving in abstinent alcoholics; modest reductions in AC were observed with a 5-HT3 antagonist, ondansetron (0.5 mg/day, but not 4 mg/day). The therapeutic potentials of these medications are being studied. For example, SUI effects on AC were enhanced by a brief psychosocial intervention. Since SUI decrease urge to drink, they may be suitable pharmacological adjuncts in relapse prevention strategies. SUI and other serotonin-altering medications are promising new neuropharmacological treatments for reducing AC.
Alcohol Alcohol Suppl 1993
PMID:Clinical pharmacology of serotonin-altering medications for decreasing alcohol consumption. 774 4

Neurochemical and neuropharmacological studies were undertaken to examine the possible involvement of the ventral tegmental area (VTA) dopamine (DA) system and the dorsal raphe nucleus (DRN) serotonin (5-HT) system in regulating oral alcohol self-administration. In vivo microdialysis studies demonstrated that either i.p. ethanol administration (1.0-2.0 g/kg) or local perfusion with ethanol (100 mM) could enhance the extracellular concentrations of both DA and 5-HT in the nucleus accumbens (ACB). Furthermore, the effects of local perfusion with ethanol on DA release in the ACB could be blocked by co-perfusion with a 5-HT3 antagonist. In the selectively-bred alcohol preferring P line of rats, there appears to be abnormal 5-HT and/or DA systems in certain limbic structures, i.e., ACB, olfactory tubercles (OTU) and medial prefrontal cortex (MPF). This is indicated by (a) lower contents of DA and 5-HT; (b) fewer 5-HT immunostained fibers; (c) lower densities of 5-HT1B, 5-HT2 and D2 receptors; and (d) higher densities of 5-HT1A receptors in the CNS of P rats compared to the alcohol-nonpreferring NP line of rats. Neuropharmacological studies demonstrated that local microinfusion of the D2 antagonist, sulpiride, or, at low doses, the DA releaser, d-amphetamine, could increase alcohol drinking by P rats. Intracranial self-administration (ICSA) studies showed that the P line of rats, but not the NP line, will self-administer 50-150 mg% ethanol directly into the VTA. Overall, these results suggest an innate abnormal functioning of the VTA DA and DRN 5-HT systems may be key factors facilitating the rewarding actions of ethanol in the CNS of P rats.
Alcohol Alcohol Suppl 1993
PMID:CNS mechanisms of alcohol self-administration. 774 40

There was a significant increase in potassium-stimulated release of 3H-[5-HT] from hippocampal slices taken from rats withdrawn from chronic ethanol treatment, compared with control-treated rats. The anxiogenic behaviour observed 12 h after ethanol withdrawal was inhibited by the 5-HT1A partial agonist, buspirone (200 micrograms/kg s.c.), indicating that the increased 5-HT release might underlie the anxiogenic response. The ex-ethanol treated rats showed impaired habituation of motor activity in the holeboard and a reduced exploratory response. The latter, but not the former, were reversed by the 5-HT3 receptor antagonist, ondansetron (0.01 microgram/kg i.p.). Ondansetron was without effect on working memory errors, but significantly increased the number of reference memory errors made by the ex-ethanol group. It also had a significantly anxiogenic effect in this group. These results suggest that the chronic ethanol treatment changes the 5-HT system and has long-lasting effects on the function of 5-HT3 receptors.
Alcohol Alcohol Suppl 1993
PMID:The role of 5-HT in the anxiogenic effects of acute ethanol withdrawal and in the long-lasting cognitive deficits. 774 45

6-Hydroxydopamine (6-OHDA) was administered ICV to Wistar male rats. Lesioned animals displayed lower preference for ethanol (ETOH) than sham-operated rats. Among 6-OHDA lesioned rats only 9% became high-preferring whereas 20% of sham-operated animals became high-preferring ones. Both tropisetron (the antagonist of 5-HT3 receptors) and 8-OHDPAT (the 5-HT1A receptor agonist) reduced ETOH drinking in high-preferring rats. However, in 6-OHDA lesioned rats the effect of tropisetron was reduced although 8-OHDA retained its effect on ETOH consumption. These results suggest that brain DA neurons are involved in tropisetron action but are not responsible for antipreference effect of 8-OHDPAT.
Alcohol
PMID:Alcohol drinking in rats injected ICV with 6-OHDA: effect of 8-OHDPAT and tropisetron (ICS 205930). 777 62

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.
Alcohol
PMID:Influence of the 5-HT1A receptor agonist ipsapirone on voluntary alcohol intake in rats. 781


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