koki.hu

RATIONALE: The serotonergic system and the hypothalamus-hypophysis-adrenocortical axis reciprocally influence each other. Therefore, the interaction between stress and serotonergic anxiolytics should be of major concern for both laboratory investigations and clinical treatment. OBJECTIVES: We have studied the effects of the serotonergic anxiolytic buspirone in rats in which basal levels of glucocorticoids were low and stable, while acute stress reactions were inhibited or exogenously induced. METHODS: Rats were adrenalectomised. Subcutaneous corticosterone pellets maintained basal glucocorticoid concentrations while acute changes were mimicked by corticosterone injections. Anxiety was assessed by the social interaction test. Temporal changes were evaluated by submitting rats to the same manipulations three times at two-day intervals. RESULTS: Buspirone applied to animals with stable and low plasma glucocorticoid concentrations induced a dramatic increase in social interactions. A slight locomotor suppressive effect was also noticed. The effects of buspirone proved to be stable over time in these animals. Acute treatment with corticosterone doubled the locomotor suppressive effects of buspirone and reversed its anxiolytic effects: the buspirone-corticosterone combination was anxiogenic after the first application. During the second and third treatment, the impact of corticosterone on buspirone efficacy gradually decreased, but the combined treatment remained about half as effective in reducing anxiety as buspirone alone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11605098&dopt=Abstract buspirone Buspar




Brain Res Dev Brain Res. 2001 Nov 26;131(1-2):9-15.
Astrocyte-mediated trophic support of developing serotonin neurons: effects of ethanol, buspirone, and S100B.

Eriksen JL, Druse MJ.

The Neuroscience Program and Division of Molecular & Cellular Biochemistry, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA.

Previously, this laboratory demonstrated that the development of serotonin (5-HT) neurons and S100B-immunopositive glia proximal to these neurons is impaired in the offspring of ethanol-fed rats. However, maternal treatment with a 5-HT(1A) agonist, e.g., buspirone or ipsapirone, between gestational days 13 and 20 prevented most of the ethanol-associated changes to developing 5-HT neurons and S100B-immunopositive glia in offspring. The present in vitro studies examined the hypothesis that the protective effects of a 5-HT(1A) agonist on ethanol-exposed, developing 5-HT neurons are mediated in part by astrocyte-produced factors such as S100B. Primary cultures of fetal 5-HT neurons were maintained in conditioned medium (CM) that was obtained from ethanol- and buspirone-treated astrocytes. In order to assess the potential contribution of S100B to the protective effects of buspirone, a mouse monoclonal antibody to S100B was added to the CM to block the biological effects of this protein. These studies demonstrated that CM, obtained from ethanol-treated astrocytes, was unable to support normal development of 5-HT neurons; there was a significant reduction in the number of 5-HT neurons/well. However, CM that was obtained from astrocytes that were co-treated with buspirone and ethanol prevented the ethanol-associated reduction, and the protective effects of buspirone required S100B. We also investigated whether exogenous S100B could protect 5-HT neurons from damage caused by direct exposure to ethanol. Direct exposure of fetal brainstem neurons to ethanol in chemically-defined medium was associated with a significant reduction in the number of 5-HT immunopositive neurons/well. Howeve

buzon.main.conacyt.mx

The effect of the 5-HT1A agonists ipsapirone (5 mg/kg), buspirone (5 mg/kg) and 8-OH-DPAT (0.5 mg/kg) on experimental anxiety was examined in sham-operated, adrenalectomized and adrenally demedullated male rats. The animal model of anxiety used was the defensive burying test. At the doses selected, all 5-HT1A compounds produced an anxiolytic-like action by reducing the burying behavior in both sham-operated and demedullated rats. However, in adrenalectomized subjects, while 8-OH-DPAT still reduced burying behavior, ipsapirone and buspirone lost their action. Data suggest that adrenocortical secretions play a role in the anxiolytic-like actions of buspirone and ipsapirone, but not in those of 8-OH-DPAT. Buspirone and ipsapirone also produced a reduction in burying behavior latency in sham-operated animals that was not observed in adrenalectomized or adrenally demedullated rats. These data suggest that adrenaline may be participating in the action of these compounds on the burying behavior latency. Present findings support possible direct relationships between the stimulation of 5-HT1A receptors and adrenal secretions.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10341368&dopt=Abstract buspirone Buspar




Braz J Med Biol Res. 2002 Feb;35(2):237-42.
Acute buspirone abolishes the expression of behavioral dopaminergic supersensitivity in mice.

Queiroz CM, Alcantara FB, Yague AM, Bibancos T, Frussa-Filho R.

Departamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brasil.

Previous studies have shown that rats withdrawn from long-term treatment with dopamine receptor blockers exhibit dopaminergic supersensitivity, which can be behaviorally evaluated by enhanced general activity observed in an open-field. Recently, it has been reported that co-treatment with the non-benzodiazepine anxiolytic buspirone attenuates the development of haloperidol-induced dopaminergic supersensitivity measured by open-field behavior of rats. The aims of the present study were: 1) to determine, as previously reported for rats, if mice withdrawn from long-term neuroleptic treatment would also develop dopaminergic supersensitivity using open-field behavior as an experimental paradigm, and 2) to examine if acute buspirone administration would attenuate the expression of this behavioral dopaminergic supersensitivity. Withdrawal from long-term haloperidol treatment (2.5 mg/kg, once daily, for 20 days) induced a significant (30%) increase in ambulation frequency (i.e., number of squares crossed in 5-min observation sessions) but did not modify rearing frequency or immobility duration in 3-month-old EPM-M1 male mice observed in the open-field apparatus. Acute intraperitoneal injection of buspirone (3.0 and 10 but not 1.0 mg/kg, 12-13 animals per group) 30 min before open-field exposure abolished the increase in locomotion frequency induced by haloperidol withdrawal. These data suggest that the open-field behavior of mice can be used to detect dopaminergic supersensitivity, whose expression is abolished by acute buspirone administration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11847528&dopt=Abstract buspirone Buspar




Acta Pol Pharm. 2001 Sep-Oct;58(5):319-23.
Estimation of buspirone-bovine serum albumin binding by affinity capillary electrophoresis.

Markuszewski M, Frackowiak T, Kaliszan R.

Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Poland.

Drug-protein binding is an important process in pharmacokinetic phase of drug action. Capillary electrophoresis was employed, specifically the Hummel-Dreyer method and Scatchard analysis, to study the interactions of an anxiolytic drug, buspirone, with pure bovine serum albumin (BSA) and with BSA present in the human recombinant 5-HT(1A) serotonin receptor preparation. The binding constant of buspirone with BSA determined in free BSA solution was K = 5.55 x 10(4) M(-1) whereas its value with BSA present in the serotonin receptor preparation was K = 5.57 x 10(4) M(-1). The method was found to be inadequate for measuring the specific binding interactions between buspirone and the 5-HT(1A) receptor in the preparation employed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11876437&dopt=Abstract buspirone Buspar

psych.med.ufl.edu

The hypothermia produced by 5-HT1A agonists had initially been claimed to be caused by the activation of cell body 5-HT1A autoreceptors resulting in decreased 5-HT transmission in laboratory animals. In order to address this issue in humans, 12 healthy volunteers underwent a dietary tryptophan depletion paradigm to decrease 5-HT availability, under double-blind conditions, during which body temperature was monitored following oral administration of the 5-HT1A agonist buspirone (30 mg). In addition, plasma prolactin and growth hormone evaluations, two responses that are mediated via the direct activation of postsynaptic 5-HT1A receptors, were determined. The hypothesis was that if responses are mediated by decreased transmission at postsynaptic 5-HT1A receptors, resulting from dampened 5-HT release as a consequence of 5-HT1A autoreceptors activation, then responses to the exogenous 5-HT1A agonist should be attenuated when 5-HT availability has been markedly decreased beforehand. Buspirone produced the same significant increase in prolactin and growth hormone in the tryptophan-depleted state as in the control condition. Similarly, the degree of hypothermia produced by buspirone was not significantly different in the two experimental conditions. In conclusion, these results strongly suggest that the hypothermia and the increases in prolactin and growth hormone produced by buspirone are attributable to the enhanced activation of postsynaptic 5-HT1A receptors, and not to a decrease in 5-HT transmission resulting from the activation of the 5-HT1A cell body autoreceptors on 5-HT neurons.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12093604&dopt=Abstract buspirone Buspar




Eur J Neurosci. 1992;4(12):1203-1212. Links
The Effect of Apomorphine and Buspirone on Regional Cerebral Blood Flow During the Performance of a Cognitive Task-Measuring Neuromodulatory Effects of Psychotropic Drugs in Man.

Grasby PM, Friston KJ, Bench CJ, Frith CD, Paulesu E, Cowen PJ, Liddle PF, Frackowiak RS, Dolan R.

MRC Cyclotron Unit, Hammersmith Hospital, DuCane Road, London W12 0HS, UK.

Psychopharmacological activation, in conjunction with positron emission tomographic measurements of regional cerebral blood flow (rCBF), was used to investigate the neurotransmitter basis of a specific cognitive function in man. Monoaminergic neurotransmission was pharmacologically manipulated during performance of auditory - verbal memory tasks. Statistical parametric mapping was used to identify the brain sites of interaction between memory-induced increases in rCBF and active drugs. Memory task-induced increases in rCBF in the left prefrontal cortex were attenuated by apomorphine, a non-selective dopamine agonist, whilst buspirone, a serotonin1A partial agonist, augmented rCBF increases in this area. In addition, apomorphine and buspirone augmented memory-induced increases in rCBF centred in the posterior cingulate cortex, whilst buspirone alone attenuated rCBF increases in the retrosplenial cortex and posterior parahippocampal gyrus. These regionally selective interactions may represent neuromodulatory effects of monoaminergic neurotransmission on a specific cognitive function in man.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12106383&dopt=Abstract buspirone Buspar

Merck.com

The selective and systemically active antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)pyridine (MPEP) was shown to display anxiolytic-like activity in a number of unconditioned assays of stress and anxiety (elevated plus maze, shock probe burying, marble burying, social interaction, and stress-induced hyperthermia) in rodents. In this report, we extend these observations found using unconditioned models of anxiety to include three models of conditioned anxiety, comparing the activity of MPEP to the clinically used anxiolytics, diazepam, and buspirone. MPEP and diazepam, but not buspirone, showed anxiolytic-like activity in the fear-potentiated startle (FPS) model. In a conditioned ultrasonic vocalization (USV) procedure, MPEP, diazepam, and buspirone reduced vocalizations to a similar degree. In the modified Geller-Seifter procedure, MPEP, diazepam, and buspirone displayed statistically significant anxiolytic-like activity, increasing the number of punished responses. Thus, these findings confirm and extend previous reports that MPEP exhibits anxiolytic-like activity in rats, and suggests that development of mGluR5 antagonists may provide a novel approach to treating anxiety disorders.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12117590&dopt=Abstract buspirone Buspar