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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonergic agents in general and the 5-HT1A agonist 8-OH DPAT in particular, reduce alcohol intake in rats and primates but the mechanism of this effect is not known. Previous studies have shown a correlation between alcohol consumption and the propensity to consume sweet substances. Indeed, certain biochemical events accompanying glucose utilization have been proposed as satiety signals in the control of feeding. Since 8-OH DPAT produces hyperglycemia, we tested the hypothesis that its effect on alcohol intake may be partly mediated through an increase blood glucose. Male Wistar rats were trained to drink a bout of 6% (w/v) alcohol using the limited access procedure which offers a daily 40-min access to alcohol and water. On consecutive test trial days separated by intervening non-drug days, the amount of alcohol consumed (1 g/kg on intervening days) was measured following the administration of 8-OH DPAT (150 micrograms/kg 10 min prior to drinking) alone or in combination with the prior (20 min) injection of idazoxan (2 mg/kg), an alpha-2 adrenoceptor antagonist with hypoglycemic properties. Idazoxan attenuated the hyperglycemic effect of 8-OH DPAT and completely reversed 8-OH DPAT's inhibitory effect on alcohol intake. Idazoxan alone produced a mild hypoglycemia and stimulated alcohol intake. These results support a role for glucoregulatory processes in serotonergically-mediated changes in alcohol consumption.
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PMID:The reduction in alcohol intake by the 5-HT1A agonist 8-OH DPAT and its attenuation by the alpha 2 adrenergic antagonist idazoxan correlates with blood glucose levels. 934 84

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.
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PMID:Selective inhibition of alcohol intake in diverse alcohol-preferring rat strains by the 5-HT2A antagonists amperozide and FG 5974. 939 17

We have previously reported that the serotonin 5-HT1A agonist 8-OH-DPAT and the 5-HT2c agonist TFMPP impair performance on a water maze. In the present report we extended those studies by examining a second 5-HT1A agonist, buspirone, to see whether its effects paralleled those of 8-OH-DPAT, and by testing the effects of the 5-HT2 agonist DOI. Unlike the open pool Morris water maze, the maze used in these experiments has alleys and doorways. The maze can be easily reconfigured to present rats with both previously learned or new maze challenges. Performance is assessed by time to reach the maze exit platform and the number of wrong doorways entered (errors). At doses that did not affect performance in a previously learned maze, the 5-HT1A agonists 8-OH-DPAT (0.1 mg/kg) and buspirone (1 mg/kg) slowed acquisition of a new maze configuration as measured by both swim time to the exit platform and errors committed. A higher dose of buspirone (10 mg/kg) completely blocked acquisition of a novel maze. In contrast. DOI slowed performance as assessed by swim time on both a well-learned maze as well as acquisition of a new maze, but did not affect error rate on either task, suggesting that this 5-HT2 agonist impaired performance by depressing motor activity. These experiments demonstrate that serotonin agonists, especially the 5-HT1A subtype, can impair learning.
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PMID:Effects of the serotonin agonists 8-OH-DPAT, buspirone, and DOI on water maze performance. 951 79

We found previously that alcohol-preferring (P) rats have fewer serotonin (5-HT) neurons and fibers in key brain regions than alcohol-nonpreferring (NP) rats. Because 5-HT uptake blockers increase synaptic 5-HT content and 5-HT1A receptor antagonists increase 5-HT release by disinhibiting 5-HT autoinnervation, in the present study, our intent was to determine whether increased synaptic 5-HT content and/or 5-HT release in P rats would effectively reduce alcohol consumption. In experiment 1, the 5-HT antagonist WAY 100635 (WAY) was tested on adult female P rats maintained on 24-hr free-choice access to ethanol (10% v/v) and water. Twice daily doses of WAY (0.05, 0.1, 0.5, and 1.0 mg/kg, subcutaneously) were administered to each rat in a counterbalanced order. Baseline ethanol intake, derived from the mean ethanol intakes of the three previous non-drug days, was approximately 8 g/kg/day. Results indicated that 0.05, 0.1, and 0.5 mg/kg doses of WAY reduced 24-hr ethanol drinking by 25-30% (p < 0.01) without affecting 24-hr water intake or body weight. In the second experiment, the effects of WAY (0.5 mg/kg), fluoxetine (1.0 mg/kg), or a combination of both were tested in another group of female P rats. WAY and fluoxetine, each alone, reduced ethanol drinking by around 20% and, when combined, decreased ethanol intake by 50%, whereas the body weight and the total fluid intake were not significantly affected. Taken together, these results indicate that both fluoxetine and WAY preferentially reduce ethanol drinking in the P line of rats and, when administered together, reduce ethanol intake in an additive manner. It is proposed that coadministration of these two compounds with distinct mechanisms of action may be a new strategy for reducing alcohol intake.
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PMID:Additive reduction of alcohol drinking by 5-HT1A antagonist WAY 100635 and serotonin uptake blocker fluoxetine in alcohol-preferring P rats. 951 17

Behavioral effects of 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-be nzodioxole HCl (MKC-242), a novel 5-HT1A-receptor agonist, were evaluated using animal models of anxiety and obsessive compulsive disorder and compared against reference compounds. MKC-242 suppressed foot shock-induced fighting behavior without loss of motor coordination in mice as the reference compounds did. The ED50 values of MKC-242, buspirone, tandospirone and diazepam were 1.7, 42, 80 and 2.0 mg/kg, p.o., respectively. The duration of the suppression of fighting by MKC-242 was longer than those of buspirone and tandospirone and comparable to that of diazepam. Similar results were also obtained with the water-lick conflict test in rats. The plasma concentration of MKC-242 in rats was much higher than the reported value of buspirone during 0.25-6 hr after oral administration. In addition, MKC-242 reduced marble burying behavior without reduction of motor activity. Fluoxetine, tandospirone and diazepam also reduced the behavior at non-sedative doses. These findings indicate that MKC-242 possesses a longer-lasting anxiolytic effect than azapirones. This might be due to the high concentration of the compound in plasma. In addition, it is also suggested that MKC-242 possesses an antiobsessional effect.
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PMID:Effect of 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole HCl (MKC-242), a novel 5-HT1A-receptor agonist, on aggressive behavior and marble burying behavior in mice. 959 23

Serotonin (5-HT) afferents may modulate the dopamine mesoaccumbens circuit, which has been shown to be critically involved in the locomotor stimulatory, discriminative stimulus, and rewarding properties of cocaine. In the present study, we investigated the role of 5-HT1A receptors in the ventral tegmental area (VTA) in mediating the discriminative stimulus effects of cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task. After acquiring the cocaine-saline discrimination, rats were stereotaxically implanted with bilateral guide cannulae into the VTA or adjacent substantia nigra reticulata (SNR). Intraperitoneal administration of cocaine (0.625-10 mg/kg) produced a dose-related increase in drug-lever responding. Both intra-VTA and intra-SNR infusion of cocaine (12.5-50 microg/0.5 microl/side) engendered primarily saline-like responding. Microinjection of the 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (DPAT; 0.1-10 microg/0.5 microl/side) or the 5-HT1A antagonist WAY 100635 (0.01-1.0 microg/0.5 microl/side) into the VTA or SNR did not substitute for the systemic cocaine cue. Further, intra-VTA or intra-SNR DPAT or WAY 100635 in combination with systemic doses of cocaine did not alter (i.e., attenuate or potentiate) the systemic cocaine cue. Overall, these data indicate that 5-HT1A receptors in the VTA do not mediate or modulate the discriminative stimulus effects of cocaine in the rat.
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PMID:The discriminative stimulus properties of cocaine: effects of microinfusion of cocaine, a 5-HT1A agonist or antagonist, into the ventral tegmental area. 963 50

Both 5-HT1A and 5-HT2A receptors have been implicated in modulating ethanol self-administration. A novel serotonergic compound, FG 5974, with combined 5-HT1A agonist/5-HT2A antagonist activities, has shown effects in decreasing ethanol consumption in two-bottle choice paradigms. In the present study, the effect of this compound on operant responding for ethanol (as well as water and a saccharin solution) was compared to compounds possessing the separate neuropharmacological effects of this drug (the 5-HT1A agonist, 8-OH-DPAT, and the 5-HT2A antagonist, amperozide). While all three serotonergic compounds decreased operant responding for ethanol, only FG 5974 had no effect on water and saccharin responding. These results suggest that combined 5HT1A agonist/5-HT2A antagonist activity provides a more selective effect on ethanol reinforcement than either neuropharmacological action alone. Therefore, further analysis of mixed serotonergic compounds in general, and FG 5974 in particular, is warranted as they offer potential treatments for alcoholism.
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PMID:Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol. 963 53

In a series of experiments, we investigated the interaction between the calcium channel antagonist, nifedipine, and the 5-HT1A agonist, ipsapirone. In the first experiment, we demonstrated that nifedipine (20 mg/kg), and to a lesser extent nimodipine (20 mg/kg), exerted an anxiolytic-like effect as did diazepam (5 mg/kg) in an experimental paradigm based on water consumption in a novel environment. In the second experiment, nifedipine (1.25, 2.5, and 5 mg/kg), and in the third experiment, ipsapirone (1.5. 3.0, and 6.0 mg/kg), have been found to exert a dose-dependent effect in the same test. Finally, a small and ineffective dose of ipsapirone (1.5 mg/kg) potentiated the anxiolytic-like effect of various doses of nifedipine. The data obtained are discussed in terms of the potential anxiolytic-like action of calcium channel antagonists and in relation to their electrophysiological effects. Moreover, the interaction between ipsapirone and nifedipine is discussed in terms of the possible involvement of central serotonergic systems in the behavioral effects of the calcium channel antagonists.
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PMID:Potential serotonergic interactions with the anxiolytic-like effects of calcium channel antagonists. 963 18

Corticosterone influences 5-HT1A receptor-mediated responses in the rat hippocampus in vitro: activation of the high affinity mineralocorticoid receptor suppresses 5-HT1A receptor-mediated hyperpolarization, while subsequent activation of lower affinity glucocorticoid receptors enhances the effect of 5-HT. We have tested whether a similar effect of corticosterone exists in vivo. In intact rats, a systemic injection of the specific 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), led to increased locomotion and to a less persistent search strategy in the free swim trial of the Morris water maze test. Adrenalectomized rats with a corticosterone-pellet implanted as replacement received an injection of vehicle (predominant mineralocorticoid receptor occupation) or a high dose of corticosterone (both corticosteroid receptor types occupied) 1 h before injection of 8-OH-DPAT. The effect on search strategy, but not on locomotor activity, was less in animals with low corticosterone levels. The results suggest that hippocampal 5-HT1A receptor-mediated responses in vivo are attenuated during predominant activation of the mineralocorticoid receptor and increased after additional transient activation of the glucocorticoid receptor.
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PMID:Acute rise in corticosterone facilitates 5-HT(1A) receptor-mediated behavioural responses. 969 99

Serotonin (5-HT) receptor agonists, antagonists, and mixed agonist/antagonists have been implicated in the volitional intake of ethanol in the rat and other species. The present experiments were undertaken to determine whether FG5938 (1-[4-(p-fluorophenyl)butyl]-4-(6-methyl-2-pyridinyl)-piperazine fumarate) would alter ethanol drinking in: genetic ethanol preferring (P) rats; and a new strain of high ethanol preferring (HEP) male and female rats derived from crossbreeding of P and a variant strain of Sprague-Dawley animals. After a preference test for solutions of 3 to 30% ethanol vs. water, each rat was given limited access to its maximally preferred concentration daily between 1600 and 1800 h; fluid intakes were recorded every 0.25 h. Once fluid consumption had stabilized over 4 days, saline vehicle, 2.5 mg/kg or 5.0 mg/kg FG5938 was injected subcutaneously 0.5 h prior to ethanol access on each of 3 consecutive days; thereafter, preference testing for ethanol continued for 4 additional days. Whereas the saline vehicle was without effect, FG5938 caused a fivefold decrease in total intake of ethanol from 1.7 to 0.3 g/kg and in proportion of ethanol to total fluid consumed from 0.42 to 0.03. The onset of the significant decline in ethanol drinking occurred during the latter 1.75-h interval. Further, both doses of FG5938, but not saline, increased the intake of food significantly. The decline in ethanol drinking was virtually identical in both P and HEP males and in female HEP rats. These results demonstrate that FG5938 affects ethanol drinking only after 0.5 h of its administration. Finally, it is envisaged that the ingestion of ethanol in genetic high drinking rats is mediated, in part, by central synapses utilizing both 5-HT1A and 5-HT2A receptors.
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PMID:Limited access to ethanol in genetic drinking rats is suppressed while feeding is enhanced by the mixed 5-HT1A agonist/5-HT2A antagonist FG5938. 970 Sep 64


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