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)

To investigate a dopaminergic component in the discriminative stimulus properties of buspirone, rats were trained to discriminate 2.5 mg/kg buspirone from saline, using a two lever, food-rewarded, fixed ratio 10 operant procedure. To test the dopamine-2 (D2) antagonist action of buspirone, a second group of rats was trained to discriminate 0.16 mg/kg apomorphine from saline. In addition to a complete generalization to 8-OH-DPAT, the D2 antagonists haloperidol, R 79598 and sulpiride showed a partial generalization to buspirone. The benzodiazepine ligands chlordiazepoxide and bretazenil did not generalize to the buspirone cue. Buspirone (2.0 mg/kg) completely blocked the apomorphine cue in the apomorphine trained rats. Haloperidol, R 79895 and sulpiride also blocked the apomorphine cue, although at doses much smaller than the doses needed to evoke buspirone responding in the buspirone trained group. 8-OH-DPAT did not antagonize apomorphine. It was concluded that the D2 action of buspirone partially contributes to its discriminative stimulus properties. Mediation of the buspirone cue by 5-HT1a receptor activation seemed predominant. Further, buspirone can act as a full D2 antagonist in drug discrimination. A model was proposed suggesting a compound discriminative stimulus complex of buspirone with a dominant 5-HT1a component that overshadows a less pronounced D2 component.
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PMID:The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity. 787 Sep 34

In the present experiments, the effects of the azapirone anxiolytics, buspirone and ipsapirone, on excessive drinking induced by a FT-60 schedule of food delivery (schedule induced polydipsia, SIP) were investigated. Because buspirone is known to block dopamine receptors and both buspirone and ipsapirone act as agonists at the 5-HT1A receptor, their effects on polydipsia were compared to raclopride, an antagonist at D2 receptors, and 8-OH-DPAT, an agonist at the 5-HT1A receptor, thus providing information about the relative importance of the serotonergic and/or dopaminergic systems for the maintenance of polydipsia. The effects of all four drugs were investigated both acutely, and following repeated treatment. The doses employed were as follows: buspirone, 1.0, 3.0, and 10.0 mg/kg; raclopride, 0.05, 0.15, and 0.5 mg/kg; 8-OH-DPAT, 0.1, and 1.0 mg/kg and ipsapirone, 1.0, 3.0, 10.0 mg/kg. Administered acutely, the lowest doses of buspirone and raclopride did not alter drinking, whilst the low dose of 8-OH-DPAT significantly reduced polydipsia. These effects were reversed following repeated treatment over 16 successive days. Buspirone 1.0 mg/kg and 0.05 mg/kg raclopride reduced drinking, whilst tolerance developed to the effects of 0.1 mg/kg 8-OH-DPAT. Ipsapirone, at low doses, was without effect on drinking. At high doses, all four drugs reduced drinking both acutely and chronically. Repeated treatment with buspirone (3.0, and 10.0 mg/kg) reduced licking and panel entries, but induced a selective decrease in licking at the low dose (1.0 mg/kg). Similar effects were seen following raclopride treatment, although the effects were less selective. 8-OH-DPAT and ipsapirone, in contrast reduced licking only at the highest dose, and both drugs increased panel entries as testing continued. The effects of buspirone resembled those of raclopride whereas the effects of ipsapirone resembled those of 8-OH-DPAT. Buspirone appears to act as a dopamine antagonist in this test. The effects of the drugs suggest that SIP depends upon motivational and performance factors which may be more sensitive to drug manipulation than potential underlying psychological factors such as anxiety or stress.
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PMID:Effects of buspirone and ipsapirone on schedule induced polydipsia: comparison with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and raclopride. 787 Oct 8

The behavioural effects of the serotonin 1A receptor (5-HT1A) agonist anxiolytics are generally examined after acute administration. The present study examined the effects of these substances during repeated treatment in the two-way active avoidance (Conditioned Avoidance Response, CAR) procedure. Previously it has been found that the prototypical 5-HT1A receptor agonist, 8-OH-DPAT, increases avoidance, apparently by increasing general activity, after repeated administration but not on acute administration. In the present study, it was demonstrated that this increase in activity can be blocked by the 5-HT1A receptor antagonists (-)alprenolol (also beta adrenergic antagonist) and (S)-UH-301, but not by the non-selective 5-HT antagonist metergoline. The relatively full 5-HT1A agonist, flesinoxan, and the partial 5-HT1A agonist, ipsapirone, had qualitatively similar effects to 8-OH-DPAT, although the effect of ipsapirone was clearly smaller in magnitude. Buspirone, the 5-HT1A partial agonist/dopamine D2 antagonist, markedly decreased activity, and thus avoidance of the shocks, in a manner similar to the antipsychotic drug, haloperidol. However, when the hypothermic effects of these compounds were investigated after acute administration, buspirone induced a strong hypothermic response in rats, like 8-OH-DPAT, whereas haloperidol had no effect. With the exception of buspirone, the effectiveness of these compounds in increasing activity in the CAR test appears to be related to their agonist efficacy at the 5-HT1A receptor. Similarities between the effects of these compounds and previously reported results with serotonin-depleting agents (Tenen 1967; Breese et al. 1974) suggest that the net effect of 5-HT1A agonists after repeated administration is to produce a functional reduction in 5-HT activity. The activity suppressing action of buspirone indicates that the dopamine antagonist activity of buspirone predominates in this procedure.
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PMID:Effects of repeated treatment with 5-HT1A agonists on active avoidance responding in the rat. 787 Oct 9

This study was designed to determine if alpha 1-adrenoceptors are involved in the vascular responses to 5-HT1A receptor agonists. Buspirone (3.1 x 10(-7)-3.1 x 10(-5) M) and 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT; 3.1 x 10(-6)-10(-4) M) elicited contractions of rabbit aorta rings which were blocked by prazosin (10(-9)-5.6 x 10(-9) M), but which were unaffected by reserpine pretreatment (1 mg/kg i.p.). 5-Methylurapidil (10(-7) and 10(-6) M) blocked contractions elicited by 8-OH-DPAT and by buspirone, whereas chloroethylchonidine (10(-5) and 10(-4) M) inhibited only the effect of buspirone. In addition, these 5-HT1A receptor agonists relaxed arteries precontracted with alpha-adrenoceptor agonists in a similar range of concentrations in which they elicited contraction. Moreover, 8-OH-DPAT and buspirone protected the alpha-adrenoceptors from the irreversible blockade provoked by phenoxybenzamine (10(-7) M), as judged by the norepinephrine contraction and stimulated phosphatidylinositol labeling. According to these results the contractile and relaxant effects elicited by 5-HT1A receptor agonists are a consequence of a direct interaction with alpha 1-adrenoceptors. The contraction elicited by 8-OH-DPAT may be mediated by alpha 1A-adrenoceptors, whereas both alpha 1A- and alpha 1B-adrenoceptors may mediate the effect of buspirone in rabbit aorta.
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PMID:Pharmacological evidence for interactions between 5-HT1A receptor agonists and subtypes of alpha 1-adrenoceptors on rabbit aorta. 790 87

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

1. The present study examined the effects of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), flesinoxan, ipsapirone and buspirone, all agonists at the 5-HT1A receptor, on the locomotor activity of guinea-pigs. The effects of these drugs were contrasted with those of the non-selective 5-HT agonist, 5-methoxy-N,N-dimethyl tryptamine (5-MeO-DMT) and the dopamine D2 antagonist, raclopride. 2. 8-OH-DPAT, flesinoxan and 5-MeO-DMT markedly increased the locomotor activity of naive, unhabituated guinea-pigs in a dose-dependent manner. Buspirone also did so, although to a lesser extent and for a shorter time. The doses at which this effect was seen were higher than those normally employed in rats. Ipsapirone and raclopride had no significant effects on locomotor activity. 3. The locomotor activity increasing effect of 1.0 mg kg-1 8-OH-DPAT was blocked by the selective 5-HT1A antagonist (S)-UH-301 (3.0 and 10.0 mg kg-1), but not by (-)-alprenolol (15.0 mg kg-1). Ipsapirone (30.0 mg kg-1) and raclopride (3.0 mg kg-1) antagonized 8-OH-DPAT-induced locomotor activity but only to a small extent. The 5-HT reuptake inhibitor, zimelidine (10.0 mg kg-1) had no effect. 4. The effect of the 5-HT1A agonists in the guinea-pig contrasts with the effects of 8-OH-DPAT on the locomotor activity of unhabituated rats and mice tested in the same apparatus, but are similar to the effects of 8-OH-DPAT on habituated rats, which show a low baseline of activity. 5. These results support the suggestion that 5-HTIA agonists may have an intrinsic activating effect which may be masked by other effects of the drug (e.g. hypothermia, 5-HT syndrome). The rank ordering of the 5-HTIA agonists also suggests that the degree to which the drugs increase locomotor activity is related to their agonist efficacy at the postsynaptic 5-HTIA receptor.
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PMID:The effect of 5-HT1A receptor agonists on locomotor activity in the guinea-pig. 792 13

1. The effects of buspirone, gepirone, ipsapirone and tandospirone on spontaneously discharging serotonergic neurons of the dorsal raphe were determined under the same experimental conditions. 2. Buspirone, gepirone, ipsapirone and tandospirone were equally efficacious and acted in a dose-dependent manner to totally inhibit the spontaneous activity of serotonergic neurons. 3. Based on their effects six min after administration (i.p.), their ED50 values were: buspirone, 134 micrograms/kg; ipsapirone, 220 micrograms/kg; gepirone, 225 micrograms/kg; tandospirone, 198 micrograms/kg. 4. The similarity of these ED50 data suggest that they share a similar chemical structure that binds to the 5-HT1A receptor, most likely it is "N-C-C-C-C-N" aliphatic backbone. 5. Buspirone and tandospirone required 4 or more min to totally block the spontaneous activity, while gepirone and ipsapirone blocked it in 3 min. 6. The dose-response curves from buspirone and tandospirone demonstrated enough dissimilarity to the dose-response curves from gepirone and ipsapirone to suggest differences in their rates of absorption, and/or differences in the production of active and inactive metabolites.
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PMID:The effects of azapirones on serotonin1A neurons of the dorsal raphe. 795 28

Brain cortex synaptoneurosomes actively incorporated [14C]arachidonic acid (AA) into lipids. Serotonin (5-HT), at a concentration range of 10 microM-1 mM, significantly stimulates the incorporation of AA mainly into phosphatidylinositol (PI) of brain cortex synaptoneurosomes. The stimulation rate of AA incorporation by 5-HT was the same in the presence and absence of lysophosphatidylinositol (LPI). However, in the absence of LPI some stimulation of AA uptake was also observed into phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid. Buspirone, an agonist of 5-HT1A receptor, has a similar effect on AA incorporation into membrane lipids as serotonin itself. Moreover, ketanserin, an antagonist of 5-HT2 receptor, also induces activation of AA incorporation into membrane lipids. On the other hand, glutamate, in a concentration dependent manner, significantly inhibits AA uptake into PI and also has some inhibitory action on AA uptake into the other lipids. Serotonin itself and the agonist of 5-HT1A receptor through the activation of AA turnover counteract glutamate-induced inhibition of AA uptake into lipids of brain cortex. Our results indicated that serotonin directly, through the specific receptors, or indirectly, through the interaction with glutamatergic receptors, modulates turnover and the level of arachidonic acid in the brain.
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PMID:Serotonin, a potent modulator of arachidonic acid turnover, interaction with glutamatergic receptor in brain cortex. 799

The cortisol response to ipsapirone (a 5-HT1A-partial agonist that produces a dose-dependent increase in plasma cortisol secretion in man) is blunted in major depression. Buspirone is another 5-HT1A agonist that increases cortisol secretion in man. This study investigated cortisol and prolactin (PRL) responses to buspirone (30 mg orally) in 45 major depressed subjects and 28 normal controls. Buspirone administration yielded a significant increase in cortisol and PRL levels in both normal controls and depressed subjects. No differences in buspirone-induced hormone responses were found either between major depressives and normal controls or between melancholic and nonmelancholic depressives. There were no significant relationships between severity of depression and any of the hormonal responses to buspirone. PRL responses to buspirone were significantly higher in women than in men.
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PMID:Effects of buspirone on plasma prolactin and cortisol levels in major depressed and normal subjects. 801

Behavioral effects of p.o. administration of SUN 8399, a selective 5-HT1A agonist, on the operant behavior under a MULT VI 1.5 min/FR 5-punishment schedule of food reinforcement and on the ambulatory activity were evaluated in mice, and the characteristics were compared with those of other 5-HT1A agonists, buspirone and tandospirone, and the benzodiazepine diazepam. Diazepam (3 and 10 mg/kg) significantly increased the punished response without eliciting any significant change in the non-punished response; i.e., showing anticonflict action. SUN 8399 (3-30 mg/kg) and buspirone (1-10 mg/kg) did not significantly change either the punished or non-punished responses. Tandospirone significantly increased the non-punished response at 10 mg/kg, but significantly decreased both the punished and non-punished responses at 30 mg/kg. The single administration of SUN 8399 (10 mg/kg), buspirone (3 and 30 mg/kg) and tandospirone (10 and 30 mg/kg) significantly increased the ambulatory activity, while diazepam tended to decrease it. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was reduced by buspirone (10 and 30 mg/kg) and tandospirone (10 and 30 mg/kg), but enhanced by diazepam (3 and 10 mg/kg). Buspirone (30 mg/kg), tandospirone (10 and 30 mg/kg) and diazepam (3 and 10 mg/kg) significantly reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.). SUN 8399 (3-100 mg/kg) did not modify the effects of either methamphetamine or scopolamine. The present results suggest that 5-HT1A agonists scarcely show anticonflict action on the Geller-type conflict behavior in mice. However, SUN 8399 possesses different behavioral characteristics from those of the other two 5-HT1A agonists in terms of interactions with methamphetamine and scopolamine.
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PMID:Effects of SUN 8399, a potent and selective 5-HT1A agonist, on conflict behavior and ambulatory activity in mice: comparison with those of buspirone, tandospirone and diazepam. 805 28


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