Synapse. 1996 Nov;24(3):240-7.
Evidence that conditioned stress enhances outflow of dopamine in rat prefrontal cortex: a search for the influence of diazepam and 5-HT1A agonists.

Wedzony K, Mackowiak M, Fijal K, Golembiowska K.

Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

We evaluated the impact of conditioned stress on outflow of dopamine in the rat prefrontal cortex. Exposure of rats to an environment associated with aversive stimuli-foot shock enhanced outflow of dopamine in a similar way as seen during the conditioning session when foot shocks were applied. Diazepam (2.5 and 10 mg/kg) dose-dependently decreased outflow of dopamine and, when given in a dose of 10 mg/kg, but not 2.5 mg/kg, decreased enhanced dopamine outflow evoked by conditioned stress. On the other hand, ipsapirone (10 mg/kg, but not 2.5 mg/kg) and buspirone (2.5 mg/kg) enhanced basal outflow of dopamine. When ipsapirone (10 mg/kg) and buspirone (2.5 mg/kg) were given to rats exposed to conditioned stress, the stress-evoked elevation in dopamine outflow was abolished. Ipsapirone in a dose of 2.5 mg/kg was ineffective in the stress paradigm tested. It is concluded that conditioned stress in vivo enhances dopaminergic neurotransmission in the rat prefrontal cortex, this effect being attenuated by diazepam, a classic anxiolytic drug, and by such novel anxiolytics as ipsapirone and buspirone, which operate via serotonergic 5-HT1A receptors. Although ipsapirone and buspirone blocked stress-induced enhancement of dopamine outflow, this effect seems to result from their influence on the basal outflow of dopamine. Differential effects of diazepam and 5-HT1A agonists on basal and stress-induced alterations in dopamine outflow are discussed in terms of their possible effectiveness in various types of general anxiety disorders.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8923664&dopt=Abstract buspirone Buspar




J Clin Pharmacol. 1996 Oct;36(10):963-9.
Lack of pharmacokinetic interaction between buspirone and haloperidol in patients with schizophrenia.

Huang HF, Jann MW, Wei FC, Chang TP, Chen JS, Juang DJ, Lin SK, Lam YW, Chien CP, Chang WH.

Taipei City Psychiatric Center, Taiwan, ROC.

The pharmacokinetic interaction between buspirone and haloperidol was evaluated in schizophrenic patients in two different groups. In both groups, haloperidol doses (10-40 mg/day) remained constant for 6 weeks before the addition of buspirone 10 mg three times daily. Serial blood samples were obtained from the 11 patients in group I at baseline (before addition of buspirone) and after administration for 24 hours. The pharmacokinetic parameters of haloperidol were determined alone and with coadministration of buspirone. In group II, buspirone 10 mg three times daily was added to treatment with haloperidol in 27 patients. Blood samples were obtained before addition of buspirone and at weeks 2 and 6 of treatment with buspirone. Samples were obtained 10 to 12 hours after administration of the evening dose and before the morning dose. Haloperidol and its metabolite, reduced haloperidol (RH), were assayed by means of high-performance liquid chromatography with electrochemical detection. Significant changes in the pharmacokinetic parameters of haloperidol were not found in group I; a mean increase in the half-life (t1/2) of haloperidol from 21.5 to 28.1 hours was observed, but this finding was not statistically significant. Under steady-state conditions, plasma levels of haloperidol in the patients in group II did not change significantly from baseline to week 6. Plasma concentrations of RH remained unaltered in both groups. The results indicate that coadministration of buspirone does not markedly affect the pharmacokinetics or plasma concentrations of haloperidol.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8930784&dopt=Abstract buspirone Buspar




J Affect Disord. 1996 Nov 4;41(1):71-6.
Increased prolactin response to buspirone in chronic fatigue syndrome.

Sharpe M, Clements A, Hawton K, Young AH, Sargent P, Cowen PJ.

University Department of Psychiatry, Warneford and Littlemore Hospitals, Oxford, UK.

We studied the endocrine and subjective responses that followed acute administration of the 5-HT1A receptor agonist buspirone (0.5 mg/kg orally) in 11 male patients with chronic fatigue syndrome (CFS) and a group of matched healthy controls. Patients with CFS had significantly higher plasma prolactin concentrations and experienced more nausea in response to buspirone than did controls. However, the growth hormone response to buspirone did not distinguish CFS patients from controls. Our data question whether the enhancement of buspirone-induced prolactin release in CFS is a consequence of increased sensitivity of post-synaptic 5-HT1A receptors. It is possible that the increased prolactin response to buspirone in CFS could reflect changes in dopamine function.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8938208&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1996 Nov;55(3):445-51.
Buspirone enhances immobility in the forced swim test in mice.

Kitamura Y, Nagatani T.

Laboratory for Pharmacology, Asahi Chemical Industry Co., Ltd., Shizuoka, Japan.

We studied the effects of buspirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on duration of immobility in mice in the forced swim test. Buspirone [3-10 mg/kg, intraperitoneally (IP)] potently and dose dependently increased the duration of immobility in mice. In contrast, following a single dose of 8-OH-DPAT (1-3 mg/kg, IP), there was a dose-dependent decrease in the duration of immobility. Pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (200 mg/kg, IP, 3 days before further drug treatment) did not alter the effects of buspirone or 8-OH-DPAT. The increase in the duration of immobility induced by buspirone (3 mg/kg, IP) was blocked by NAN-190 [1-(2-methoxyphenyl)-4-(4-[2-phthalimido]butyl)-piperazine hydrobromide, 1 mg/kg, IP], a postsynaptic 5-HT1A receptor antagonist. However, the effect of 8-OH-DPAT (1 mg/kg, IP) was not blocked by NAN-190 (1 mg/kg, IP). The effect of buspirone (3 mg/kg, IP) was blocked by apomorphine (0.3 mg/kg, IP), a dopamine receptor agonist. Based on the results of this study, it is suggested that the effects of buspirone and of 8-OH-DPAT on immobility in the forced swim test may occur through different mechanisms.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8951987&dopt=Abstract buspirone Buspar




J Intellect Disabil Res. 1996 Dec;40 ( Pt 6):502-8.
The effect of buspirone on challenging behaviour in mentally retarded patients: an open prospective multiple-case study.

Verhoeven WM, Tuinier S.

Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands.

During the past few decades, suggestive evidence has been accumulated that abnormalities in serotonin neurotransmission are involved in the pathogenesis of aggressive behaviour disorders and impulsivity. Support for this idea can be derived from clinical studies using 5-HT1 agonistic compounds and serotonergic antidepressants. In the present study, the efficacy of the 5-HT1a agonist buspirone was investigated in eight patients with mental retardation and severe, long-lasting challenging behaviour, characterized by aggressive outbursts, self-injurious behaviour and impulsivity. The findings demonstrate that buspirone, in a daily dosage varying between 20 and 50 mg, may be effective in reducing this type of behavioural disturbance and associated with an improvement in sociability. It is hypothesized that the responsiveness to buspirone treatment may be the result of a de-arousing phenomenon, mediated via corticosteroid dependent stress homeostatic mechanisms.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9004110&dopt=Abstract buspirone Buspar




Brain Res Mol Brain Res. 1995 Sep;32(2):348-53.
Chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA and binding sites in various regions of the rat hippocampus.

Chen H, Zhang L, Rubinow DR, Chuang DM.

Section on Molecular Neurobiology, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA.

Groups of rats were treated with buspirone (1 mg/kg/day) for 21 days using osmotic minipumps implanted subcutaneously. After buspirone treatment, the 5-HT1A receptor mRNA levels were significantly decreased in the CA1 and CA2 of the hippocampus, but were markedly increased in the dentate gyrus (DG), CA3 and CA4. The level of the 5-HT1A receptor binding sites was not significantly changed in these subhippocampal areas. Buspirone treatment markedly increased 5-HT2A receptor mRNA levels in the DG, CA2, CA3 and CA4. This was accompanied by a significant increase in the level of 5-HT2A receptor binding sites in all subhippocampal regions. These results demonstrate that chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA as well as their expressed binding sites in various regions of the hippocampus.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7500848&dopt=Abstract buspirone Buspar




J Neurochem. 1997 Mar;68(3):1326-9.
Buspirone enhances duloxetine- and fluoxetine-induced increases in dialysate levels of dopamine and noradrenaline, but not serotonin, in the frontal cortex of freely moving rats.

Gobert A, Rivet JM, Cistarelli JM, Millan MJ.

Psychopharmacology Department, Centre de Recherches de Croissy Croissy-sur-Seine, France.

A serotonin (5-HT)1A receptor partial agonist, buspirone, potentiates the clinical antidepressant properties of 5-HT reuptake inhibitors (SSRIs). Herein, we examined the interaction of buspirone with two SSRIs, duloxetine and fluoxetine, on extracellular levels of 5-HT, dopamine (DA), and noradrenaline (NAD) in single dialysate samples of freely moving rats. Duloxetine (5.0 mg/kg. s.c.) and fluoxetine (10.0 mg/kg, s.c.) increased dialysate levels of DA (65 and 60% vs. basal values, respectively). NAD (400 and 90%, respectively), and 5-HT (130 and 110%, respectively) in the frontal cortex (FCX). Buspirone (2.5 mg/kg, s.c.) similarly elevated levels of DA (100%) and NAD (160%) but reduced those of 5-HT (-50%). Administered with buspirone, the ability of duloxetine and fluoxetine to increase 5-HT levels was transiently inhibited (over 60 min), although by the end of sampling (180 min) their actions were fully expressed. In contrast, buspirone markedly and synergistically facilitated the elevation in DA levels elicited by duloxetine (550%) and fluoxetine (240%). Furthermore, buspirone potentiated the induction of NAD levels by duloxetine (750%) and fluoxetine (350%). These data suggest that a reinforcement in the influence of SSRIs on DA and possibly. NAD but not 5-HT release in FCX may contribute to their increased antidepressant activity in the presence of buspirone. More generally, they support the hypothesis that a reinforcement in dopaminergic transmission in the FCX contributes to the actions of SSRIs and other antidepressant drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9048781&dopt=Abstract buspirone Buspar




Brain Res Dev Brain Res. 1997 Feb 20;98(2):185-90.
5-HT1a receptors mediate the neurotrophic effect of serotonin on developing dentate granule cells.

Yan W, Wilson CC, Haring JH.

Department of Anatomy and Neurobiology, Saint Louis University Health Sciences Center, MO 63104, USA.

We have previously reported that neonatal (P3) serotonin (5-HT) depletion results in a significant decrease in the number of dendritic spines per 50 microns of dendritic length on dentate granule cells. This effect is specific and permanent. Neither total dendritic length nor the number of dendritic segments is affected by 5-HT depletion. The area dentata contains a dense 5-HT1a receptor population that is present in the at birth. Therefore, 5-HT1a receptors represented a likely candidate for the mediation of the effects of 5-HT on developing granule cells. The present study used the drugs buspirone and NAN-190, which have been shown to be an agonist and antagonist respectively at postsynaptic 5-HT1a receptors in vivo, to test the idea that neurotrophic actions of 5-HT result from 5-HT1a receptor stimulation. Following 5-HT depletion with PCA, pups received daily injections of buspirone (1.0 mg/kg) from P5 to P14. Granule cell morphology was then studied using intracellular filling with Neurobiotin on P14, P21 and P60. Buspirone treatment prevented the loss of dendritic spines previously shown to follow 5-HT depletion with PCA. No other morphological parameters were significantly changed by buspirone treatment. Naive pups received daily injections of NAN-190 from P3 to P14. One group received 1.0 mg/kg while a second group received 3.5 mg/kg. Both doses of NAN-190 resulted in dendritic spine loss comparable to that obtained with neonatal PCA treatment. This loss was permanent suggesting that the first two postnatal weeks may represent a critical period for the action of 5-HT on developing granule cells. Significant, dose-dependent changes in total dendritic length and number of dendritic segments reminiscent of the effects of