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)

Preclinical studies have contributed greatly to our understanding of the neurochemical pathways associated with the development and maintenance of alcohol-seeking behaviour. These studies have demonstrated the important role of serotonin pathways, particularly as they relate to dopaminergic function, which mediates alcohol-induced reward associated with its abuse liability. Naturally, this has led to the study of serotonergic agents as treatments for alcoholism.SSRIs do not appear to be effective treatment for a heterogeneous alcoholic group. However, they may be useful as treatment for late-onset alcoholics, or alcoholism complicated by comorbid major depression. Buspirone, a serotonin 5-HT1A partial agonist, does not appear to be an effective treatment for alcoholics without comorbid disease. Buspirone may, however, have some utility for treating alcoholics with comorbid anxiety disorder. The 5-HT2 antagonist ritanserin, at pharmacologically relevant clinical doses, does not appear to be an effective treatment for alcoholism. Ondansetron, a 5-HT3 antagonist, is an efficacious and promising medication for the treatment of early-onset alcoholism. Preliminary evidence suggests that combining the mu antagonist naltrexone with the 5-HT3 antagonist ondansetron promises to be more effective for treating alcoholism than either alone. The differential treatment effect of SSRIs and ondansetron among various subtypes of alcoholic is intriguing. Future research is needed to understand more clearly the molecular genetic differences and the interactions of such differences with the environment that typify a particular alcoholic subtype. Such an understanding could enable us to make comfortable predictions as to which alcoholic subtype might respond best to a particular serotonergic agent, which could then be provided.
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PMID:Role of the serotonergic system in the neurobiology of alcoholism: implications for treatment. 1558 81

We studied the effect of treatment with the serotonin-1A (5-HT1A) receptor ligands buspirone, 8-hydroxy-di-propyl-aminotetralin (8-OH-DPAT), and (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8-azaspiro[4,5]decane-7,9-dione methyl sulphonate (MDL73,005EF) on blood pressure and heart rate increases to open field stress. We compared Spontaneously Hypertensive Rats (SHR), Fawn-Hooded (FH) rats, Wistar-Kyoto (WKY) rats, and Sprague-Dawley (SD) rats instrumented with radio-telemetry probes. Buspirone treatment reduced the blood pressure increase in SHR, FH rats, and WKY rats and heart rate increase in FH rats and WKY rats. 8-OH-DPAT treatment reduced the blood pressure increase in FH rats and WKY rats, but had no effect in SHR and enhanced the pressor response in SD rats. This treatment reduced the heart rate increase in FH rats and WKY rats only. Similarly, MDL73,005EF treatment reduced the blood pressure increase in FH rats and WKY rats, but had no effect in SHR and enhanced this response in SD rats. Little effect of this treatment was seen on heart rate changes. For comparison, diazepam treatment abolished the pressor response in SD rats and reduced it in FH rats and WKY rats, but not SHR. Differential effects of the treatments were also seen between strains for locomotor activity in the open field, although behavioural changes could not explain the effects of the drugs on cardiovascular responses. These data suggest that 5-HT1A receptors are involved in cardiovascular stress responses; however, the extent of this involvement differs between rat strains and the drugs used. These results could be important for our understanding of possible anxiolytic properties of antipsychotic drugs with affinity for the 5-HT1A receptor.
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PMID:Involvement of serotonin1A receptors in cardiovascular responses to stress: a radio-telemetry study in four rat strains. 1565 9

Serotonin is known to inhibit food and water intake. However, the effect of its injection into nucleus caudatus on food and water intake is not known. In the present study, serotonin hydrochloride, buspirone (the serotonin 5-HT1A agonist) and ondensetron (the 5HT3 antagonist) were injected into nucleus caudatus through stereotaxically implanted cannulae in three different dosages (1, 2 and 5 microg) and their effects on 24 h food and water intake, and body weight were recorded. The injection of serotonin hydrochloride resulted in a dose- dependent decrease in food intake attaining maximum of 27.3% at 5 microg dose, whereas water intake and body weight were decreased 12% and 4.3% respectively only at the highest does. Buspirone elicited a dose dependent inhibition of food and water intake and body weight (22.3%, 19.8% and 5.1% respectively), whereas ondensetron elicited an increase in food and water intake (37.8% and 36.3% respectively) without significantly altering bodyweight. It was concluded that serotonin hydrochloride injected into nucleus caudatus inhibits food and water intake significantly. These effects are mediated via 5-HT1A and 5HT3 receptors. The effect of injections of 5-HT1A receptor agonist is more pronounced on water intake. The effect of injections of 5HT3 receptor antagonist is also more pronounced on water intake.
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PMID:Effects of injection of serotonin into nucleus caudatus on food and water intake and body weight in albino rats. 1590 52

In prior work, we have demonstrated that the behavioral effects of cocaine adhere to the predictions of the opponent-process theory of drug action. Animals develop conditioned place preferences for distinct locations paired with the immediate effects of IV cocaine, but learn to avoid places paired with the effects present 15-min post-injection. It was of interest to assess the putative role of 5-HT in producing the negative properties of cocaine since cocaine acts to inhibit the reuptake of serotonin (5-HT) and since such actions have been associated with anxiogenic consequences. Male rats were administered a reinforcing dose of cocaine (1.0 mg/kg IV) and then placed - either immediately or after a 15-min delay - into one side of a two-compartment (black-white) conditioned place preference (CPP) box for 5-min. On alternate days, the animals received IV saline injections and were placed in the opposite side of the CPP box. This continued for eight days after which animals had experienced 4 pairings of cocaine with one side (black or white) of the CPP apparatus, and 4 saline pairings with the opposite side. Other groups of rats were treated identically except that 30-min prior to placement into the apparatus, these animals received an IP injection of saline or buspirone (a partial 5-HT1A agonist) at a dose that we have shown to be anxiolytic (2.5 mg/kg IP). Control animals experienced either buspirone or saline pretreatments without cocaine. Our results confirm that animals increase the time spent on the side paired with the immediate effects of cocaine (compared to baseline), but tend to avoid the side paired with effects present 15-min post-injection. Buspirone had no effect on the immediate rewarding properties of cocaine, but completely reversed the negative properties present 15-min post-cocaine. These results are consistent with the view that attenuation of 5-HT neurotransmission (via the autoreceptor agonist properties of buspirone) can reverse the negative impact of IV cocaine.
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PMID:Effects of buspirone on the immediate positive and delayed negative properties of intravenous cocaine as measured in the conditioned place preference test. 1752 62

Buspirone is a potent anxiolytic that decreases serotonin transmission. Changes in electrolyte balance, plasma osmolality and systolic blood pressure are often associated with stress-induced anxiety in rats as well as in human but effects of buspirone on changes in serum electrolytes balance, plasma osmolality and SBP of rats has not been reported. Present study concerns the effects of different doses of buspirone (0.25, 0.5, and 1 mg/kg) on serum electrolyte, plasma osmolality and systolic blood pressure (SBP) of rats. Anxiolysis related variable are also monitored. Results show that the administration of buspirone (0.25 mg/kg and 0.5 mg/kg) significantly increased the serum concentration of electrolytes and plasma osmolality but decreased the serum level of magnesium. These doses also reduced the systolic blood pressure (SBP). A dose of 1 mg/kg buspirone produced no effect on the concentration of serum electrolytes, and plasma osmolality. Anxiolytic effects of the drug were dose dependent but 1 mg/kg dose decreased the effect. The results are discussed in the context of serotonin receptors (5-HT1A) to be involved in buspirone-induced changes of electrolytes, SBP and plasma osmolality.
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PMID:Dose related effects of buspirone on serum electrolyte balance, plasma osmolality and systolic blood pressure (SBP) in rats. 1760 52

Buspirone, a partial agonist of the serotonergic 5-HT1A receptor, improves breathing irregularities in humans with Rett syndrome or brain stem injury. The purpose of this study was to examine whether buspirone alters posthypoxic ventilatory behavior in C57BL/6J (B6) and A/J mouse strains. Measurements of ventilatory behavior were collected from unanesthetized adult male mice (n=6 for each strain) using the plethysmographic method. Mice were given intraperitoneal injections of vehicle or several doses of buspirone and exposed to 2 min of hypoxia (10% O2) followed by rapid reoxygenation (100% O2). Twenty minutes later, mice were tested for hypercapnic response (8% CO(2)-92% O2). On a separate day, mice were injected with the 5-HT1A receptor antagonist 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}-N-2-pyridinylbenzamide (p-MPPI) before the injection of buspirone, and measurements were repeated. In separate studies, arterial blood-gas analysis was performed for each strain (n=12 in B6 and 10 in A/J) with buspirone or vehicle. In both strains, buspirone stimulated ventilation at rest. In the B6 mice, the hypoxic response was unchanged, but the response to hypercapnia was reduced with buspirone (5 mg/kg; P<0.05). With reoxygenation, vehicle-treated B6 exhibited periodic breathing and greater variation in ventilation compared with A/J (P<0.01). In B6 animals, >or=3 mg/kg of buspirone reduced variation and prevented the occurrence of posthypoxic periodic breathing. Both effects were reversed by p-MPPI. Treatment effect of buspirone was not explained by a difference in resting arterial blood gases. We conclude that buspirone improves posthypoxic ventilatory irregularities in the B6 mouse through its agonist effects on the 5-HT1A receptor.
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PMID:Effects of buspirone on posthypoxic ventilatory behavior in the C57BL/6J and A/J mouse strains. 1851 27

The purpose was to examine sighs and spontaneous pauses in regard to the stability of resting breathing in the B6 strain, compared to the A/J strain. A 5-HT1A receptor agonist (buspirone) and a chromosomal substitution strain (B6a1) were used to further alter breathing patterning. Ten-minute recordings of room air breathing were collected from unanaesthetized B6, A/J, and B6a1 mice. Despite no differences between strains in the magnitude and incidence of sighs, post-sigh apneas, the variation for duration of expiration (Te) after sighs, and the number of spontaneous pauses were greater in the B6, while Shannon Entropy (nonlinear metrics) for Te after sighs was lower in B6, compared to the other strains. Buspirone and chromosomal substitution eliminated post-sigh apneas and decreased spontaneous pauses. A greater irregularity and the lower complexity of post-sigh breathing in B6 are reversed by elements on A/J chromosome 1 and by increased 5-HT1A serotonergic tone.
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PMID:Post-sigh breathing behavior and spontaneous pauses in the C57BL/6J (B6) mouse. 1856 3

New data on complex realization of anxiolytic, antidepressive and antinociceptive effects of prenatal injections of a 5-HT1A agonist buspirone were obtained in prenatally stressed adult rats. Buspirone was injected to female rats from the 9th to 21st days of pregnancy; during the last week of pregnancy buspirone was injected 10 min before immobilization stress. In the adult offspring of both sexes, behavioral indices of tonic pain response in the formalin test and the indices of depression in the forced swim test were investigated. The choice of the target was defined in accordance with available literature data on the role of 5-HT1A receptors in the mechanisms of prenatal stress, of formation of the ascending link of the nociceptive system, of development of depression, and in the mechanisms of the treatment ofnociceptive information. Prenatal stress increased the duration of licking and the time of immobility, the indices of tonic pain and depression in the rats of both sexes. Buspirone evoked the decrease of the indices investigated in prenatally stressed rats in both tests in comparison with the relevant indices in prenatally stressed rats that were not subjected to buspirone. Thereby, it has been demonstrated that buspirone normalized the indices of the tonic pain response modified by prenatal stress; a considerable decrease of the index of depression suggests that there are differences in mechanisms of antinociceptive and antidepressive effects of buspirone. The data on complex realization of anxiolytic, antidepressive and antinociceptive effects ofbuspirone stimulate the attention of clinicians and prompt further investigations in this direction.
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PMID:[Effects of prenatal influences of buspirone and stress on indices of inflammatory pain response and depressive behaviour in adult rats]. 2056 60

Previous investigations from our laboratory demonstrated that prenatal stress exacerbates inflammatory pain-related behavior in adult rats and that fetal serotonin (5-HT) is involved in this phenomenon. In the present study we test the hypothesis that injections of buspirone, a 5-HT1A agonist, to rat dams before restraint stress during the last week of pregnancy (between pregnant days 15 and 20) can improve the characteristics of emotional and inflammatory pain-related behaviors in the adult offspring. Buspirone was injected to dams between the 9 and 20 days of pregnancy, during restraint stress, five min before it. The depression-like behavior in the forced swim test, formalininduced pain and body weight were investigated in the adult offspring. Prenatal stress exacerbated the licking behavior, the index of formalin-induced pain, and increased the time of immobility, the index of depression-like behavior. Buspirone normalized the licking behavior and profoundly reduced the time of immobility, which indicates differences in the mechanisms of antinociceptive and antidepressant effects of buspirone. The present new findings demonstrate that adverse influences of prenatal stress on emotional and inflammatory pain-related behaviors can be prevented by using prenatal buspirone, which shows long-term anxiolytic, antidepressant and antinociceptive effects. The new fact of body weight decrease in buspirone+stress males is worth noting in the context of the important problem of body weight gain as a common side effect of treatment with antidepressant drugs.
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PMID:Maternal buspirone protects against the adverse effects of in utero stress on emotional and pain-related behaviors in offspring. 2105 51

The effects of buspirone were tested on rearing in an open field. Six different doses of buspirone (10, 3.3, 1.1, 0.3, 0.1 and 0.04 mg/kg) and a single dose of chlordiazepoxide (5 mg/kg) were administered i.p. to separate groups of rats. Buspirone produced a dose-dependent decrease in rearing in the range 0.04-10 mg/kg, whereas only the higher doses (10 and 3.3 mg/kg) decreased ambulation significantly. Chlordiazepoxide reduced rearing to an extent equivalent to 1 mg/kg of buspirone. Together with data in the literature, the results suggest that 5-HT1A agonists affect rearing at lower doses than ambulation; that the effects of buspirone in the open field are similar to classical anxiolytics; and that changes in rearing may be more closely related to anxiolytic than muscle relaxant, anti-convulsant and other GABA-mediated effects of the classical anxiolytics.
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PMID:Dose-response analysis of the effects of buspirone on rearing in rats. 2228 22


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