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Neuropeptide Y-like immunoreactivity (NPY-LI) was investigated in naIve Sprague-Dawley rats subjected to acute, subchronic (7 days) or chronic (21 days) intraperitoneal treatment with diazepam (1 or 3 mg/kg once daily) or buspirone (1.5 or 5 mg/kg twice daily). NPY-LI was determined by radioimmunoassay in the amygdala, nucleus accumbens, hypothalamus and frontal cortex 24 h after the last dose of the drugs. Amygdala NPY-LI decreased after acute diazepam (3 mg/kg) or buspirone (1.5 mg/kg) and increased after subchronic treatment with both doses of diazepam and after chronic buspirone (1.5 mg/kg) treatment. Both diazepam and buspirone given in subchronic and chronic doses decreased NPY-LI levels in the nucleus accumbens. Hypothalamic NPY-LI changed only after chronic treatment: it decreased after diazepam and increased after buspirone (5 mg/kg). NPY-LI content in the frontal cortex decreased after subchronic diazepam (3 mg/kg) treatment and slightly increased after buspirone. The study has shown that both diazepam and buspirone affect NPY-LI levels in rats. These results suggest that the NPY system in the amygdala and nucleus accumbens is implicated in the anxiolytic effects of the drugs studied. Copyright 1999 Harcourt Publishers Ltd.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10657538&dopt=Abstract buspirone Buspar




J Psychopharmacol. 1999 Dec;13(4):391-7.
The effects of the novel anxiolytic drug lesopitron, a full and selective 5-HT1A receptor agonist, on pupil diameter and oral temperature in man: comparison with buspirone.

Phillips MA, Szabadi E, Bradshaw CM.

Division of Psychiatry, University of Nottingham, UK.

We investigated the effects of two 5-HT1A receptor agonists, buspirone and lesopitron, upon pupil size in human volunteers at an ambient luminance level of 32 Cd m(-2) and in darkness. Pupil diameter was monitored with a binocular infrared television pupillometer, before and after the administration of treatments for 4 h at 20-min intervals. Two experiments were conducted. In Experiment 1, 14 healthy male volunteers participated in seven weekly sessions, each associated with the ingestion of one capsule (buspirone 5, 10 and 20 mg, lesopitron 10, 20 and 40 mg and placebo), according to a double-blind balanced, cross-over design. Both buspirone and lesopitron tended to decrease pupil diameter. In darkness, only the highest dose of buspirone (20 mg) caused a miosis that was statistically significant. However, at the luminance level of 32 Cd m(-2) buspirone 10 and 20 mg evoked statistically significant miotic effects, as did the highest dose of lesopitron (40 mg). The miotic effect was significantly greater at 32 Cd m(-2) than in darkness after each dose of buspirone and the highest dose (40 mg) of lesopitron. In Experiment 2, pupil diameter and oral temperature were monitored with an electronic thermometer at 40-min intervals. Twenty healthy male volunteers participated in two weekly sessions, each associated with the sublingual application of 100 microl hydroalcoholic solution (lesopitron 20 mg, placebo), according to a double-blind balanced cross-over design. Lesopitron caused a significant miosis both in darkness and at the luminance level of 32 Cd m(-2); the miosis was greater at 32 Cd m(-2) than in darkness. Lesopitron tended to decrease oral temperature; this effect however, was not statis




Pharmacol Biochem Behav. 2000 Feb;65(2):281-8.
Ethanol, but not the anxiolytic drugs buspirone and diazepam, produces a conditioned place preference in rats exposed to conditioned fear stress.

Matsuzawa S, Suzuki T, Misawa M.

Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.

The present study was designed to investigate the role of an anxiolytic effect in the development of a drug-associated place preference in rats exposed to conditioned fear stress, using the conditioned place-preference paradigm. The administration of a low dose of ethanol (300 mg/kg, IP) and the anxiolytic drugs, buspirone (1 and 2 mg/kg, IP) and diazepam (1.25 and 2.5 mg/kg, IP), did not produce a place preference in rats that were not exposed to conditioned fear stress. In rats that were exposed to conditioned fear stress, ethanol produced a significant place preference, while buspirone and diazepam failed to produce a place preference. In addition, ethanol, buspirone, and diazepam produced no place preference in rats treated with an anxiogenic dose of pentylenetetrazole (20 mg/kg, IP). A significant decrease in locomotor activity was observed in rats exposed to conditioned fear stress. Ethanol, but not buspirone and diazepam, significantly recovered or increased locomotor activity in rats exposed to conditioned fear stress. Further, the locomotor-stimulating effect of ethanol was markedly enhanced by repeated exposure to conditioned fear stress. These results suggest that the stimulating effect may be strongly related to the development of the rewarding effect of a low dose of ethanol under psychological stress, and that the conditioned place preference paradigm with conditioned fear stress may be useful for studying the rewarding mechanism of ethanol with regard to the interaction between ethanol and psychological stress.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10672981&dopt=Abstract buspirone Buspar

umontreal.ca

The effects of serotoninergic stimulation on monoamines were studied in the heterozygous Lurcher (Lc/+) mutant mouse, a model of human cerebellar ataxia. Wild type (+/+) and Lc/+ mice were treated for 40 days with L-tryptophan or buspirone, and serotonin (5-HT), dopamine (DA), noradrenaline (NA) and their main metabolites were measured in the cerebellum. In +/+ mice, only buspirone increased concentrations of 5-HT metabolites. In the hypoplastic Lc/+ cerebellum, indoleamines were higher, and increased further after both treatments. The 5-HT turnover index was increased in +/+ mice by buspirone, while in Lc/+ mutants it increased after L-tryptophan but was decreased by buspirone, indicating that in the mutants nerve terminals synthesize and accumulate 5-HT, but may not utilize it efficiently. Catecholamine contents remained unchanged in +/+ mice, but in Lc/+ mutants with higher endogenous NA, L-tryptophan further increased NA and 3,4-dihydroxy-phenylacetic acid (DOPAC), and buspirone augmented NA, DA and DOPAC levels.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10675788&dopt=Abstract buspirone Buspar

hsc.vcu.edu

5-Hydroxytryptamine(1A) (5-HT(1A)) receptors, which activate inhibitory G-proteins, are implicated in psychiatric disorders including anxiety and depression. Studies suggest that chronic 5-HT(1A) receptor agonist administration alters 5-HT(1A) receptor function, but the effect of chronic treatment on 5-HT(1A) receptor-activated G-proteins is unclear. In this study, agonist-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate (GTPgammaS) binding was examined following chronic administration of buspirone. Brains were processed for [35S]GTPgammaS autoradiography using R(+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) for 5-HT(1A) receptors or baclofen for GABA(B) receptors. Net 8-OH-DPAT-stimulated [35S]GTPgammaS binding was decreased by 25-30% in the septum and dorsal raphe nucleus of buspirone-treated animals. No significant changes in 8-OH-DPAT-stimulated [35S]GTPgammaS binding were found in the prefrontal, entorhinal or cingulate cortices or hippocampus in buspirone-treated rats. GABA(B) receptor-stimulated [35S]GTPgammaS binding was increased by 25% in the hippocampus, with no significant changes in any other region examined. These results demonstrate region-specific alterations in 5-HT(1A) and GABA(B) receptor-activated G-proteins following chronic buspirone treatment, which may contribute to the clinical effects of this drug.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10688978&dopt=Abstract buspirone Buspar




J Chromatogr Sci. 2000 Apr;38(4):151-6.
Liquid chromatographic method for the analysis of buspirone HCl and its potential impurities.

Kartal M, Khedr A, Sakr A.

College of Pharmacy, University of Cincinnati, OH 45267-0004, USA.

An accurate, reproducible, and sensitive method for the determination of buspirone HCl and its potential impurities is developed and validated. The validated liquid chromaography method is conducted to meet the Food and Drug Administration/ International Conference on Harmonization requirements for the analysis of buspirone HCI in the presence of its impurities. Five buspirone HCI potential impurities, including 1-(2-pyrimidinyl)-piperazine (I), propargyl chloride (II), 3,3'-tetramethylene glutarimide (III), propargyl glutarimide (IV), and the Mannich base-condensate of I-IV fumarate (V), are separated using a microBondapack C18 column by gradient elution with a flow rate 2.0 mL/min. The initial mobile phase composition is 90:10 (v/v) 10mM KH2PO4 (pH 6.1)-acetonitrile. After a 1-min initial hold, a linear gradient is performed in 26 min to 35:65 (v/v) 10mM KH2PO4 (pH 6.1)-acetonitrile. The samples are detected at 210 and 240 nm using a photo-diode array detector. The linear range of detection for buspirone HCI was between 1.25 ng/microL and 500 ng/microL, with a limit of quantification of 1.25 ng/microL. The linearity, range, peak purity, selectivity, system performance parameters, precision, accuracy, and robustness for all of the impurities were also shown to have acceptable values.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10766481&dopt=Abstract buspirone Buspar




Behav Pharmacol. 2000 Apr;11(2):153-60.
Alnespirone and buspirone have anxiolytic-like effects in a conflict procedure in rats by stimulating 5-HT(1A) receptors.

Cervo L, Munoz C, Bertaglia A, Samanin R.

Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

We studied the anxiolytic-like activity of alnespirone and buspirone, two 5-HT(1A) receptor agonists, in a modified Geller-Seifter conflict model, and examined the role of 5-HT(1A) receptors by studying whether WAY-100635, a selective antagonist at these receptors, blocked their effects. Administered s.c. 30 minutes before testing, 0.5 and 1mg/kg alnespirone significantly increased punished responding, whereas lower doses (0.125 and 0.25 mg/kg) had no effect. At 1mg/kg, alnespirone significantly reduced the rates of unpunished responding. One dose of buspirone (1mg/kg) significantly increased punished responding and reduced unpunished responding. Lower doses were ineffective. Administered s.c. 40 minutes before testing, WAY-100635 had no effect on any parameter but completely antagonized the effects of alnespirone (1mg/kg) and buspirone (1mg/kg) on punished responding. The ability of buspirone to reduce unpunished responding was not antagonized by WAY-100635, probably reflecting a sedative effect of buspirone due to dopamine D2 receptor blockade. The results suggest that alnespirone and buspirone have anxiolytic-like activity in a conflict procedure by stimulating 5-HT(1A) receptors, presumably at a presynaptic level. Like buspirone, alnespirone may have useful effects in the treatment of anxiety disorders.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10877120&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 2000 Jun;66(2):389-96.
Inhibitory effect of buspirone and diazepam, but not of 8-OH-DPAT, on maternal behavior and aggression.

Ferreira A, Picazo O, Uriarte N, Pereira M, Fernandez-Guasti A.

Departamento de Farmacologia y Toxicologia, CINVESTAV/IPN and Division de Investigaciones en Neurociencias, IMP, D.F., Mexico, Mexico.

The action of diazepam (0.0, 1.0, and 2.0 mg/kg) and the serotonergic compounds buspirone (0.0, 2.5, and 5.0 mg/kg) and 8-OH-DPAT (0.0, 0.1, and 1.0 mg/kg) on maternal behavior and aggression were studied. An activity test was made after these treatments to control for unspecific actions due to motor impairment. Diazepam and buspirone dose-dependently inhibited the expression of maternal aggression and the active components of maternal behavior such as retrieving and nest building. 8-OH-DPAT did not affect these behaviors. 8-OH-DPAT (1.0 mg/kg) provoked the serotonergic syndrome and hypothermia; however, ovariectomized animals showed more signs of the syndrome and a decrease in body temperature after 8-OH-DPAT than lactating rats. Buspirone, but not the other anxiolytics, reduced motor activity. The role of drugs acting at the serotonergic, dopaminergic, and GABA-benzodiazepine systems in the control of maternal behavior and aggression is discussed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10880695&dopt=Abstract buspirone Buspar