Jpn J Pharmacol. 1994 Apr;64(4):273-80.
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.

Kuribara H.

Department of Neurobiology and Behavior, Gunma University School of Medicine, Maebashi, Japan.

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 ot




Neuroscience. 1994 May;60(2):441-51.
Pharmacological suppression of the median raphe nucleus with serotonin1A agonists, 8-OH-DPAT and buspirone, produces hippocampal theta rhythm in the rat.

Vertes RP, Kinney GG, Kocsis B, Fortin WJ.

Center for Complex Systems, Florida Atlantic University, Boca Raton 33431.

The effects on the hippocampal electroencephalogram of microinjections of procaine hydrochloride and the serotonin1A agonists, 8-OH-DPAT and buspirone, into the median raphe nucleus were examined in the urethane anesthetized rat. Injections of procaine, 8-OH-DPAT or buspirone into the median raphe nucleus produced a change in the hippocampal electroencephalogram from a spontaneous desynchronized pattern to a synchronized pattern (theta rhythm) within short latencies and for long durations post-injection. Procaine was shown to elicit theta at a mean latency of 52 s and for a mean duration of 21.75 min; buspirone at a mean latency of 2 min and for a mean duration of 34.5 min. A dose dependent relationship was observed between 8-OH-DPAT injections and latencies but not durations. Small doses (0.5 micrograms) of 8-OH-DPAT produced theta at a mean latency of 1.33 min and large doses (3.0 micrograms) at a mean latency of 1.17 min. 8-OH-DPAT injections generated theta for a mean duration of 62 min. Injections of each of these substances into structures dorsal, lateral or rostrocaudal to the median raphe (dorsal raphe nucleus, pontine reticular formation, caudal linear nucleus or raphe pontis, respectively) failed to generate theta or in a few cases produced theta at very long latencies (> 24 min). Saline injections in the median raphe nucleus or control structures were without effect. The demonstration that agents injected into the median raphe nucleus that inhibit its activity (procaine and serotonin1A agonists) produce theta indicate that serotonin-containing median raphe neurons normally suppress theta or are involved in the control of hippocampal desynchronization. The present finding




Neurochem Res. 1994 Mar;19(3):249-55.
8-[3H]hydroxy-2-(di-n-propylamino) tetralin binding sites in goldfish retina.

Lima L, Schmeer C, Urbina M.

Laboratorio de Neuroquimica, Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas.

The binding sites of 8-[3H]hydroxy-2-(di-n-propylamino)tetralin ([3H]DPAT) were characterized in the retina of goldfish in order to evaluate the selectivity of the ligand for serotonin1A (5HT1A) receptors. Specificity of the binding was performed in the presence of serotonergic and dopaminergic agonists and antagonists. Buspirone, spiroxatrine and 5-methoxy-N,N-dimethyltryptamine were potent inhibitors, followed by propranolol, citalopram, imipramine and desipramine. Serotonin was not a potent inhibitor, and its interaction with the binding sites of [3H]DPAT was complex. Nomifensine displayed an important inhibition, however, other dopamine uptake blockers, such as bupropion and GBR-12909, were less potent. Haloperidol was also a good inhibitor, but the D1 receptor agonist, SKF-38393, the D2 receptor antagonist, sulpiride, and dopamine did not inhibit the binding. GppNHp inhibited the binding in the micromolar range. The analysis of saturation experiments by isotopic dilution, using buspirone to determine nonspecific binding, revealed two sites. The number of binding sites defined by buspirone were higher than the ones defined by nomifensine. The specific binding, using buspirone for definition, was reduced by the intraocular injection of 6-hydroxydopamine. This investigation demonstrates that [3H]DPAT labels 5HT1A receptors in goldfish retina, but also interacts with a non-5HT receptor site. These receptors seem to be localized in dopaminergic neurons.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8177365&dopt=Abstract buspirone Buspar




J Clin Psychopharmacol. 1994 Apr;14(2):126-30.
Buspirone's efficacy in organic-induced aggression.

Stanislav SW, Fabre T, Crismon ML, Childs A.

College of Pharmacy, University of Texas at Austin 78712.

The objectives of this study were to (1) identify and characterize hospitalized patients with an organic-related psychiatric diagnosis who had received buspirone therapy and (2) assess the effect of buspirone on aggressive behaviors. A retrospective medical records review was conducted on all patients who were admitted to our psychiatric/rehabilitation facility over a 36-month period and who had received buspirone therapy. Monthly behavioral therapy records were used to determine the quality and quantity of aggressive-related behaviors. Study endpoint was reached in each subject when buspirone was discontinued or when records were unavailable. Twenty subjects, ranging in age from 15 to 55 years old (mu = 26.1 +/- 9.8), were identified for study. Nine (90%) of 10 subjects for whom data were available for at least 3 months showed an improvement in behavior by study endpoint, and 6 (60%) showed at least a 50% reduction in behavioral symptoms by study endpoint. Results from this study suggest that buspirone is well tolerated and may be effective in the treatment of aggressive and other maladaptive behaviors in individuals with an organic component to their psychiatric illness, particularly traumatic brain injury. Prospective, controlled trials are needed to validate these findings.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8195453&dopt=Abstract buspirone Buspar




Br J Psychiatry. 1994 Mar;164(3):372-9.
5-HT1A receptor sensitivity in major depression. A neuroendocrine study with buspirone.

Cowen PJ, Power AC, Ware CJ, Anderson IM.

Psychopharmacology Research Unit, Littlemore Hospital, Oxford.

The hypothermic, growth hormone and corticotrophin (ACTH) responses to the 5-HT1A receptor agonist buspirone (30 mg orally) were measured in 20 unmedicated patients with major depression and 20 healthy controls. Compared with the controls, the hypothermic responses of the depressed patients to buspirone were significantly attenuated, particularly in patients with melancholic depression. In contrast, the responses of growth hormone and ACTH to buspirone were unchanged. The data suggest that major depression may be associated with impaired sensitivity of 5-HT1A autoreceptors but that the function of the post-synaptic 5-HT1A receptors that mediate growth hormone and ACTH release is unaltered. Within the limitations that attend the use of buspirone as a 5-HT1A probe, our data suggest that the decrement in serotonin neurotransmission at post-synaptic 5-HT1A receptors in depression is due to decreased serotonin release rather than impaired responsivity of post-synaptic 5-HT1A receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8199791&dopt=Abstract buspirone Buspar




Eur J Pharmacol. 1994 Mar 3;253(3):297-301.
Buspirone enhances head twitch behavior in mice.

Kitamura Y, Nagatani T, Watanabe T.

First Laboratory for Pharmacological Research, Asahi Chemical Industry Co., Ltd., Miyazaki, Japan.

We studied the effects of buspirone, a 5-HT1A receptor agonist, on head twitch behavior induced by 5-hydroxy-L-tryptophan (5-HTP) administered together with pargyline in mice. Buspirone dose dependently (0.1-10 mg/kg i.p.) enhanced head twitch behavior. This effect was blocked by (-)-propranolol and NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine hydrobromide). The enhancing effect of buspirone was also observed when mice were pretreated with p-chlorophenylalanine. These findings suggest that the enhancing effect of buspirone on head twitch behavior may be exerted through the activation of post-synaptic 5-HT1A receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8200425&dopt=Abstract buspirone Buspar




Arch Int Pharmacodyn Ther. 1995 May-Jun;329(3):347-59.
Effects of the 5-hydroxytryptamine1A receptor agonists, 8-OH-DPAT, buspirone and flesinoxan, upon brain damage induced by transient global cerebral ischaemia in gerbils.

Piera MJ, Beaughard M, Michelin MT, Massingham R.

Riom Laboratoires-CERM, Service de Pharmacologie, France.

The effects of the 5-hydroxytryptamine1A agonists, 8-OH-DPAT, buspirone and flesinoxan, on the delayed hyperactivity and on the ensuing neuronal degeneration induced by transient global cerebral ischaemia, were studied. In normothermic, male Mongolian gerbils, subjected to 3 min bilateral carotid artery ligation, the locomotor activity was measured 1 day after ischaemia. The neuronal damage was quantified 7 days later using an image analysis system. Buspirone (3 and 10 mg/kg, i.p.) and flesinoxan (1 and 3 mg/kg, i.p.), administered twice a day for 3 days both in pre- and post-ischaemic conditions, failed to significantly protect the CA1 zone of the hippocampus against neuronal damage. In contrast, 8-OH-DPat (1 and 3 mg/kg, i.p.) significantly reduced the neuronal degeneration. All compounds abolished the hyperactivity but there was no correlation between this parameter and the extent of the reduction in neuronal damage. The ineffectiveness of buspirone and flesinoxan was not the result of too low a dose - as evidenced by the complete inhibition of hyperactivity with both compounds and by the appearance of a serotonin behavior syndrome with flesinoxan - but is possibly related to a partial agonist activity at the 5-hydroxytryptamine1A receptor, as reported for buspirone. Further studies are necessary to explain the differences between these agonists.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8546535&dopt=Abstract buspirone Buspar




Eur J Pharmacol. 1995 Jul 14;280(3):277-84.
Differential effect of buspirone and diazepam on negative contrast in one-way avoidance learning.

Torres C, Morales A, Candido A, Maldonado A.

Departamento de Psicologia Experimental y Fisiologia del Comportamiento, Universidad de Granada, Spain.

The main aim of the present work was to investigate the effect of buspirone, a 5-HT1A receptor agonist, on successive negative contrast in one-way avoidance learning. Successive negative contrast was induced by shifting rats from a large reward (30 s spent in the safe compartment) to a small reward (1 s). Acute administration of buspirone (0.25, 0.5, 0.75 and 1.0 mg/kg i.p.) did not attenuate the contrast effect, as opposed to that observed for diazepam (1 mg/kg i.p.). The highest dose of buspirone used, however, did interfere with the learning of the avoidance response itself. Chronic buspirone (20 days, 0.5 and 0.75 mg/kg i.p.) did not have any effect on successive negative contrast either. Overall, these results could suggest that the 5-HT1A receptor is not involved in the negative contrast effect studied, quite different to that observed for the gamma-aminobutyric acid (GABA) system. The findings are compared to results obtained with animal models selectively sensitive to some anxiolytic drugs, as are the so-called 'conflict models'.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8566095&dopt=Abstract buspirone Buspar