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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 acute or chronic ethanol on serotonin (5-HT)-induced membrane hyperpolarization and inhibition of the slow Ca2(+)-dependent after hyperpolarization (sAHP) were recorded in rat CA1 pyramidal neurons in hippocampal slices using sharp intracellular electrodes. 5-HT (1-100 microM) caused concentration-dependent hyperpolarization of the membrane that was not altered by simultaneous 30 mM ethanol treatment, but blunted by 10 microM buspirone, a weak 5-HT1A agonist. 5-HT (1-30 microM) also partially inhibited (approximately 40%) the sAHP following a burst of five or more action potentials. Initially ethanol (30 mM) alone did not alter the sAHP, but over a period of 38 min, a slow increase in amplitude (approximately 40%) was observed. 5-HT-mediated inhibition of the sAHP was significantly greater with ethanol present, regardless of the length of exposure. Pyramidal neurons in hippocampal slices prepared from ethanol-dependent animals showed no obvious signs of withdrawal related hyperexcitability and neither concentration-dependent membrane hyperpolarization nor sAHP inhibition caused by 5-HT were significantly changed from responses in controls. These results suggest that hyperpolarizing responses to 5-HT in hippocampal CA1 pyramidal neurons are functionally resistant to acute or chronic ethanol treatment. 5-HT-mediated inhibition of the sAHP is enhanced by ethanol acutely, but does not show an adaptive change as a result of ethanol dependence.
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PMID:Acute and chronic actions of ethanol on CA1 hippocampal responses to serotonin. 888 49

Agents affecting serotonergic (5-hydroxytryptamine, 5-HT) function influence ethanol consumption in rats and primates. In the present study female Sprague-Dawley rats were trained to orally self-administer 8% ethanol (v/v) in a large operant chamber in a 60-min test period by a prandial drinking technique. The number of response, ethanol reinforcers (dipper deliveries), and ethanol consumption (g/kg) were measured following administration of the 5-HT1 A agonist 8-OH-DPAT (0.001 1.0 mg/kg, ip) 30 min prior to testing. Locomotor activity (LMA) was also measured to assess activity changes induced by 8-OH-DPAT. 8-OH-DPAT selectively reduced ethanol ingestion from 17.1 +/- 3.2 dipper deliveries under vehicle conditions to 6.6 +/- 3 at a dose of 0.1 mg/kg. Higher doses of 8-OH-DPAT (0.5 and 1.0 mg/kg) significantly reduced both ethanol ingestion and LMA. Lower doses of 0.001-0.01 mg/kg of 8-OH-DPAT were without effect on ethanol intake and maintained behavior. These results demonstrate that, under the present experimental conditions, the 5-HT1A receptor agonist 8-OH-DPAT reduced ethanol self-administration in the rat, and support a role for 5-HT1A receptors in the mediation of ethanol reinforcement.
Alcohol
PMID:The 5-HT1A receptor agonist 8-OH-DPAT reduces ethanol intake and maintained behavior in female Sprague-Dawley rats. 888 35

The neurotransmitter serotonin (5-HT) has long been implicated in the etiology of aberrant consumption of alcohol. Several compounds thought to possess a potential therapeutic value to counteract drinking have high affinities for 5-HT1A and 5-HT2A receptors in the brain. For example, amperozide and FG5865 significantly reduce the volitional intake of alcohol, without altering food intake, both in rats genetically predisposed or chemically induced to drink alcohol. The present study was undertaken in the alcohol-preferring (P) rat to determine whether an amperozide like drug. FG5938 (1-[4-(p-fluorophenyl)butyl]-4-(6-methyl-2-pyridinyl)-piperazine fumarate). exerts an action on the volitional drinking of alcohol as well as on the intakes of food and water. In 11 male P rats, the pattern of preference for different concentrations of alcohol was determined by an 11-day test for water vs. 3 to 30% alcohol solutions. After maximally preferred alcohol concentrations, i.e., 9 to 15% had stabilized for 4 days, saline or FG5938 was injected subcutaneously at 1600 and 2200 h in a dose of 2.5, 5.0, or 10.0 mg/kg over 4 consecutive days. Following treatment, preference testing for the same concentrations of alcohol was continued for 5 additional days. FG5938 caused a significant suppression in alcohol drinking in terms of both absolute g/kg and proportion to total fluid intake. During its administration, FG5938 also enhanced the ingestion of food and water of the P animals significantly, with the largest intake occurring on the initial day, while body weights increased. After FG5938 injections, food and water intakes returned to predrug levels. The saline control vehicle had no significant effect on the intakes of alcohol, food, or water of the P rats. Overall, these results show that FG5938 acts to attenuate alcohol preference while simultaneously increasing the ingestion of food paradoxically. To our knowledge, this is the first known drug to possess this unique property. Finally, these findings support the view that a compound having affinities to both 5-HT1A and 5-HT2A receptors may be useful as a therapeutic agent in the treatment of alcoholism.
Alcohol
PMID:The mixed 5-HT 1A/2A receptor drug FG5938 suppresses alcohol drinking while enhancing feeding in P rats. 888 50

In the present study, we found that local application of serotonin (5-HT) potentiated ethanol-induced depressions of the spontaneous activity of Purkinje neurons in urethane-anesthetized rats. 5-HT also potentiated depressions induced by gamma-aminobutyric acid; however, this modulatory response was quantitatively smaller than 5-HT-induced potentiation of ethanol depression. Previous reports suggested that the release of 5-HT can be regulated by presynaptic 5-HT autoreceptors. We found that local application of methiothepin, which may induce 5-HT overflow through the inhibition of presynaptic autoreceptors, facilitated ethanol-mediated responses. This methiothepin effect was greatly diminished in neonatally 5,7-dihydroxytryptamine-lesioned animals, suggesting a presynaptic mechanism was involved. We also found that the 5-HT1A antagonist UH301 did not attenuate 5-HT-facilitated ethanol reactions. On the other hand, local application of 5-HT1B agonist CGS12066B potentiated ethanol-induced depression. Taken together, our data suggest that 5-HT can modulate ethanol-mediated electrophysiological depression, possibly mediated through 5-HT1B receptors in the cerebellum.
Alcohol Clin Exp Res 1996 Oct
PMID:Serotonin modulates ethanol-induced depression in cerebellar Purkinje neurons. 890 76

This study extends the pharmacological characterization of a novel quantitative murine behavioral method, the mirrored chamber aversion assay, which appears to be selectively sensitive to anxiolytic agents. Behavioral effects of acute diazepam administration were compared with those of the 5-HT1A anxiolytic buspirone and those of ethanol in C57BL/6J mice. These known anxiolytics produced a dose-dependent reduction in avoidance behavior of large magnitude, as evidenced by statistically significant decreases in latency to enter and increases in time spent in the mirrored chamber. Anxiolytic-like effects of these compounds in the mirrored chamber assay differed from those observed by the elevated plus-maze method. The behavioral effects of the test compounds were not due to alteration of locomotor activity. These findings indicate that the murine mirrored chamber assay responds to several agents known to be anxiolytic in man but differs from the plus-maze in the pharmacological spectrum of the anxiolytics to which it is sensitive.
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PMID:Anxiolytics by ethanol, diazepam and buspirone in a novel murine behavioral assay. 890 69

Rats trained to discriminate ethanol (EtOH, 1 g/kg IP) from saline in a two-lever procedure completely generalized to the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and paroxetine. Substitution of fluoxetine was completely blocked by the selective 5-HT2A receptor antagonist MDL 100,907 and not affected by the selective 5-HT1A receptor antagonist WAY-100635. It is suggested that the previously reported effectiveness of SSRIs in reducing EtOH consumption could be based on similarities in discriminative stimulus effects of SSRIs and EtOH. Stimulation of 5-HT2A receptors may underlie these stimulus similarities and contribute to the EtOH intake-reducing effects of SSRIs.
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PMID:Substitution of the selective serotonin reuptake inhibitors fluoxetine and paroxetine for the discriminative stimulus effects of ethanol in rats. 916 Aug 58

Previously, it was shown that in utero ethanol exposure results in decreased serotonin (5-HT) and altered concentrations of 5-HT reuptake sites and 5-HT1A receptors in fetal and/or postnatal rats. Because fetal 5-HT is an essential trophic factor, this laboratory previously investigated the hypotheses that the early ethanol-associated 5-HT deficit contributed to subsequent development abnormalities in the serotonergic system and that the effects of the fetal 5-HT deficit could be prevented by maternal treatment with buspirone, a 5-HT1A receptor agonist. The present report determined the effects of maternal treatment with buspirone on two other neurotransmitter systems in the developing offspring of ethanol-fed dams: dopamine (DA) and norepinephrine reuptake sites and D1 receptors in postnatal day 19 offspring of control and ethanol-fed dams, that received daily injections of saline or 4.5 mg/kg buspirone. These investigations found that in utero ethanol exposure significantly decreased norepinephrine reuptake sites in the dorsomedial hypothalamic nucleus and anteroventral thalamic nucleus. There was also an ethanol effect in the dorsal raphe. D1 receptors were moderately increased (5-10% increase) in the striatum, and DA reuptake sites were unchanged in PN19 ethanol-exposed offspring. No other significant ethanol-related effects were noted. Maternal buspirone treatment did not adversely affect the concentration of DA reuptake sites or D1 receptors in control rats. Thus, whereas buspirone exerts protective effects on the developing 5-HT system of ethanol-exposed rats, it does not appear to damage the development of the DA system. Maternal buspirone produced only one significant abnormality in control offspring; it resulted in significant reduction of norepinephrine reuptake sites in the DR.
Alcohol Clin Exp Res 1997 05
PMID:Effects of maternal ethanol consumption and buspirone treatment on dopamine and norepinephrine reuptake sites and D1 receptors in offspring. 916 5

A drug discrimination procedure was used to characterize the ethanol-like effects of a variety of 5-HT1 agonists. Previous studies found that the degree of substitution of the 5-HT1B/2C agonist TFMPP (m-trifluoromethylphenylpiperazine) depended on the training dose of ethanol. The present studies extend this initial finding to four additional 5-HT agonists with different selectivity for 5-HT1A, 5-HT1B, or 5-HT2C receptors: CGS 12066B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2a]quinoxaline maleate), mCPP [1-(3-chlorophenyl)piperazine diHCl], RU 24969 [5-methoxy-3(1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole succinate and 8-OH DPAT [(+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr]. Separate groups of rats were trained to discriminate 1.0 g/kg (n = 7), 1.5 g/kg (n = 6) or 2.0 g/kg (n = 8) ethanol from water. Following training, three to five doses of each 5-HT agonist were tested twice in each rat. The most selective 5-HT1B agonist tested, CGS 12066B (3-17 mg/kg; IP), completely substituted for the 1.0 g/kg ethanol, but not for 1.5 or 2.0 g/kg ethanol. Likewise, the 5-HT1B/2C agonist mCPP (0.56-1.7 mg/kg; IP) completely substituted only in the 1.0 g/kg ethanol training group. The 5-HT1A/1B agonist RU 24969 (0.1-3.0 mg/kg; IP) substituted for all training doses of ethanol, although in a lower proportion of the rats tested in the 2.0 g/kg ethanol training group. Finally, the 5-HT1A agonist 8-OH DPAT (0.1-1.0 mg/kg, IP) did not substitute completely for any ethanol training dose. The results consistently show that agonists with 5-HT1B activity produce discriminative stimulus effects similar to low and intermediate, but not high, ethanol training doses.
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PMID:Characterization of the ethanol-like discriminative stimulus effects of 5-HT receptor agonists as a function of ethanol training dose. 934 79

In utero ethanol exposure results in a decreased concentration of serotonin (5-HT) in brain regions containing the cell bodies of 5-HT neurons and their cortical projections. The concentration of 5-HT reuptake sites is also reduced in several brain areas. The present study extended prior work by evaluating the effects of chronic maternal ethanol consumption and maternal buspirone treatment on 5-HT1A and 5-HT2A receptors in multiple brain areas of offspring. Receptors were quantitated early in postnatal development and at an age when the 5-HT networks are normally well-established. Because fetal 5-HT functions as an essential neurotrophic factor, these studies also determined whether treatment of pregnant rats with buspirone, a 5-HT1A agonist, could overcome the effects of the fetal 5-HT deficit and prevent ethanol-associated receptor abnormalities. The results demonstrated that in utero ethanol exposure significantly alters the binding of 0.1 nM [3H]-8-hydroxy-dipropylaminotetralin to 5-HT1A receptors in developing animals. Ethanol impaired the development of 5-HT1A receptors in the frontal cortex, parietal cortex, and lateral septum; these receptors did not undergo the normal developmental increase between postnatal days 19 and 35. The dentate gyrus was also sensitive to the effects of in utero ethanol exposure. 5-HT1A receptors were increased in this region at 19 days. Maternal buspirone treatment prevented the ethanol-associated abnormalities in 5-HT1A receptors in the dentate gyrus, frontal cortex, and lateral septum. Neither maternal ethanol consumption nor buspirone treatment altered the binding of 2 nM [3H]ketanserin to 5-HT2A receptors in the ventral dentate gyrus, dorsal raphe, parietal and frontal cortexes, striatum, substantia nigra, or nucleus accumbens.
Alcohol Clin Exp Res 1997 Oct
PMID:Effects of maternal ethanol consumption and buspirone treatment on 5-HT1A and 5-HT2A receptors in offspring. 934 75

The present studies sought to elucidate the role of 5-HT2A receptor antagonists in suppressing alcohol intake by comparing the effects of amperozide and FG 5974 on alcohol, food, and water intake in strains of alcohol-preferring rats: P, Alko Alcohol (AA), and Fawn-Hooded (FH). Both amperozide and FG 5974 have 5-HT2A receptor antagonist properties, but FG 5974 also shows presynaptic 5-HT1A receptor agonist activity. After establishment of stable baselines for intake measures in a two-bottle continuous access paradigm, rats (n = 10) were injected with 1 of 5 doses (0, 2.5, 5.0, and 10.0 mg/kg, sc) of amperozide or FG 5974 at weekly intervals. Amperozide dose-dependently reduced alcohol intake, total fluid intake, and alcohol preference in all three strains under continuous access conditions, whereas FG 5974 was less effective. Food intake was also suppressed by amperozide at higher doses, whereas it was increased by FG 5974. Amperozide also dose-dependently reduced alcohol intake when it was available for only 1 hr/day, but FG 5974 tended to increase it. After oral administration, amperozide was also more effective than FG 5974 in reducing alcohol intake. Despite these differences in efficacy in suppressing alcohol intake, both compounds produced taste aversion to a novel saccharin solution. These complex findings suggest that biochemical properties other than 5-HT2A receptor antagonism (e.g., 5-HT1A receptor agonism) may be involved in the effects of amperozide and FG 5974 on alcohol intake and other consummatory behaviors.
Alcohol Clin Exp Res 1997 Nov
PMID:Selective inhibition of alcohol intake in diverse alcohol-preferring rat strains by the 5-HT2A antagonists amperozide and FG 5974. 939 17


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