Pharmacol Biochem Behav. 1998 Feb;59(2):387-97.
Effects of propranolol, buspirone, pCPA, reserpine, and chlordiazepoxide on open-field behavior.

Angrini M, Leslie JC, Shephard RA.

School of Behavioural Sciences, University of Ulster at Coleraine, Northern Ireland, UK.

The study examined the possibility that propranolol, buspirone, pCPA, and reserpine have antianxiety effects by comparing their effects with those of chlordiazepoxide on an open-field test of emotionality in rats. The effects of intraperitoneal injections of d,l, propranolol (5, 10, 20 mg/kg), buspirone (1.25, 2.5, 5 mg/kg), reserpine (0.5 mg/kg), parachlorophenylalanine (pCPA) (100 mg/kg), and chlordiazepoxide (CDP) (2.5, 5, 10 mg/kg) were compared with performance of rats under saline or water using an open-field test on 5 successive days. Significant effects were found on peripheral movements, rearing, grooming, immobility, and defecation. The patterns of effects of high doses of propranolol and buspirone resembled those of CDP, while pCPA had some of the effects of CDP, and reserpine produced few effects. With propranolol, buspirone, and CDP, there was evidence of dose sensitivity. The effects of repeated testing across 5 days were different from these of CDP or other drugs. The results are consistent with the hypothesis that the effects of propranolol and buspirone on open-field behavior are anxiolytic, and may be mediated by action on the same brain systems.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9476986&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1998 Mar;59(3):729-35.
Effects of the serotonin agonists 8-OH-DPAT, buspirone, and DOI on water maze performance.

Kant GJ, Wylie RM, Chu K, Ghosh S.

Division of Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.

We have previously reported that the serotonin 5-HT1A agonist 8-OH-DPAT and the 5-HT2c agonist TFMPP impair performance on a water maze. In the present report we extended those studies by examining a second 5-HT1A agonist, buspirone, to see whether its effects paralleled those of 8-OH-DPAT, and by testing the effects of the 5-HT2 agonist DOI. Unlike the open pool Morris water maze, the maze used in these experiments has alleys and doorways. The maze can be easily reconfigured to present rats with both previously learned or new maze challenges. Performance is assessed by time to reach the maze exit platform and the number of wrong doorways entered (errors). At doses that did not affect performance in a previously learned maze, the 5-HT1A agonists 8-OH-DPAT (0.1 mg/kg) and buspirone (1 mg/kg) slowed acquisition of a new maze configuration as measured by both swim time to the exit platform and errors committed. A higher dose of buspirone (10 mg/kg) completely blocked acquisition of a novel maze. In contrast. DOI slowed performance as assessed by swim time on both a well-learned maze as well as acquisition of a new maze, but did not affect error rate on either task, suggesting that this 5-HT2 agonist impaired performance by depressing motor activity. These experiments demonstrate that serotonin agonists, especially the 5-HT1A subtype, can impair learning.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9512079&dopt=Abstract buspirone Buspar




J Physiol Pharmacol. 1998 Mar;49(1):175-85.
The effects of buspirone on the behaviour of control and stressed mice.

Pokk P, Zharkovsky A.

Department of Pharmacology, University of Tartu, Estonia.

The effects of buspirone on the locomotor activity and behaviour in the plus-maze and hole-board tests were studied in control and small platform stressed mice. Small platform stress for 24 hours increased the locomotor activity of mice and induced anxiolytic-like effect in the plus-maze and hole-board tests. Administration of buspirone either did not affect (2.0 and 4.0 mg/kg) or inhibited (8.0 mg/kg) locomotions in control animals. The inhibition of locomotor activity by buspirone was greater in small platform stressed mice. In control mice buspirone in doses 2.0 and 4.0 mg/kg exerted anxiolytic effect in the plus-maze and hole board test that was reflected by an increase in the percentage of entries onto and the percentage of time spent on the open arms of the plus-maze and increased number of head-dippings in the hole-board test. In contrast, in small platform stressed mice, buspirone did not induce anxiolytic action in the plus-maze and hole-board tests at any dose tested. In doses 2.0 and 4.0 mg/kg buspirone produced a sedative effect that was reflected by a decrease in the total number of entries made onto the open and into the closed arms of the plus-maze and a decrease in the number of head-dippings and rearings in the hole-board test. These data suggest that small platform stress induces a sensitization of mice to the motor depressant effect of buspirone. At the same time small platform stress induces hyposensitivity to the anxiolytic effect of buspirone. It is proposed that these changes might be due to alterations in the serotonergic transmission or to changes in the release of corticosterone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9594420&dopt=Abstract buspirone Buspar




Chin J Physiol. 1998;41(1):33-44.
Buspirone impaired acquisition and retention in avoidance tasks: involvement of the hippocampus.

Liang KC, Tsui KY, Tyan YM, Chiang TC.

Department of Psychology, National Taiwan University, Taipei, ROC.

This study investigated the effects of buspirone on acquisition as well as formation and expression of memory in three different types of avoidance tasks. Rats were trained and tested on a one-trial inhibitory avoidance task, an 8-trial active avoidance task or the Morris water maze. Buspirone (5.0 mg/kg) was administered subcutaneously 30 min before training, immediately after training or 30 min before testing. Retention was tested at various times after training. In the inhibitory avoidance task, pretraining injections of buspirone produced a marked impairing effect on retention, posttraining injections of buspirone produced a moderate but time-dependent memory deficit. Pretest injections of buspirone suppressed retention performance. Such an effect was more pronounced in the 1-day test than in the 21-day test. Intra-hippocampal infusion of buspirone (5.0 micrograms) before testing suppressed expression of the 1-day, but not the 21-day, memory. In the active avoidance task and the Morris water maze, an injection of buspirone before training or testing also impaired acquisition or suppressed retention performance. These findings suggest that buspirone given at various times could compromise acquisition, consolidation and retrieval of affective memory and the hippocampus was involved in the retrieval effect.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9629480&dopt=Abstract buspirone Buspar




Psychopharmacology (Berl). 1998 Jul;138(1):16-26.
Buspirone is differentiated from diazepam in humans using a three-response drug discrimination procedure.

Frey JM, Mintzer MZ, Rush CR, Griffiths RR.

Department of Psychiatry and Behavioral Sciences, Behavioral Biology Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.

The discriminative stimulus effects of buspirone and diazepam were examined in 12 healthy volunteers using a three-response drug discrimination procedure and a within-subject design. During an initial sampling phase, the training drug conditions (placebo, 15 mg/70 kg buspirone, and 10 mg/70 kg diazepam) were identified to subjects by letter codes before oral drug administration. During a subsequent training phase, subjects earned money for correct drug identifications made two hours after drug administration. Ten out of 12 subjects acquired the three-response discrimination. When lower doses of buspirone (3.75 and 7.5 mg/70 kg) and diazepam (2.5 and 5.0 mg/70 kg) were tested in a subsequent generalization testing phase, both buspirone and diazepam produced dose-related increases in appropriate drug identifications, without significant cross-generalization. Analyses of standardized and unstructured self report questionnaires revealed that buspirone and diazepam produced different profiles of effects, and that buspirone was associated with a number of "negative" subject-rated effects including tension, nausea, and dizziness. These results demonstrate a distinct profile of discriminative stimulus and subjective effects for buspirone relative to diazepam which is consistent with its distinct pharmacological profile, and provide evidence for the sensitivity of the three-response drug discrimination procedure.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9694522&dopt=Abstract buspirone Buspar

compuserve.com

The present series of experiments compared the behavioral effects of the novel non-peptide CRF antagonist CP-154,526 with those of diazepam and the 5-HT1A receptor partial agonist buspirone in classical animal models of anxiety including conflict tests (punished lever pressing and punished drinking tests in rats) and exploratory models (elevated plus-maze test in rats, light/dark choice and free-exploration tests in mice), and a recently developed mouse defense test battery (MDTB) which has been validated for the screening of anxiolytic drugs. Results from both conflict procedures showed that diazepam (2.5-10 mg/kg, i.p.) produced clear anxiolytic-like effects, whereas buspirone (2.5 mg/kg, i.p.) displayed anticonflict activity in the punished drinking test only. CP-154,526 (0.6-20 mg/kg) was devoid of significant activity in both procedures. In the elevated plus-maze, diazepam (2 mg/kg, i.p.) produced significant effects on traditional (i.e. spatio-temporal) and ethologically derived (i.e. risk assessment and directed exploration) indices of anxiety. Buspirone (1-4 mg/kg, i.p.) reduced risk assessment activities only, and CP-154,526 (0.6-20 mg/kg, i.p.) did not modify the indices of anxiety in the elevated plus-maze. In the light/dark test, diazepam (2.5-5 mg/kg, i.p.) and CP-154,526 (10-40 mg/kg, i.p.) affected all behavioral indices of anxiety, while buspirone reduced risk assessment activities at the highest doses only (10 and 15 mg/kg, i.p.). In the free-exploration test, diazepam (1 mg/kg, i.p.) reduced avoidance responses towards novelty, as indicated by the increase in exploratory activity in a novel compartment and the decrease in risk assessment. CP-154,526

servier.fr

RS-30199 has been shown previously to have atypical interactions at 5-HT1A receptors. RS-30199 and RS-64459, an analogue of buspirone with a buspirone side chain, were compared with the classic, partial agonist at 5-HT1A receptors, 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) and buspirone. At human (h) 5-HT1A receptors in CHO cells, RS-30199-193 (racemate) and its enantiomers (-197, -198) inhibited [3H]-8-OH-DPAT binding (RS-30199-198, ki, 29.7 +/- 11.7 nM; RS-30199-197, ki, 74.1 +/- 11.7 nM) as did RS-64459 (ki, 24.9 +/- 6.0 nM), but RS-30199-197 and -198 were almost full agonists in a [35S]-GTPgammaS binding assay, whereas RS-64459 was a partial agonist, resembling buspirone and 8-OH-DPAT. RS-64459 and the enantiomers of RS-30199 had weaker affinity for 5-HT2C and 5-HT7 receptors. These compounds did not induce the 5-HT behavioural syndrome in male rats. However, in a model where naive male rats were introduced to estrogen-progesterone primed, sexually receptive female rats, RS-30199-197 (0.1, 1, 10 mg/kg, s.c.) had a profound inhibitory effect on sexual behaviour score. Neither buspirone nor 8-OH-DPAT reduced the sexual behaviour score. Unlike 8-OH-DPAT, which shortens intromission latency, RS-30199 prolonged intromission latency. RS-30199 (10 mg/kg s.c.) fully inhibited the facilitation of sexual behaviour caused by the alpha2-adrenoceptor antagonist, delequamine (0.1 mg/kg, p.o.). In contrast, RS-64459 (100, 250, 1000 and 4000 microg/kg, s.c.) failed to modify the sexual behaviour score and did not modify intromission latency. The differences between the effects of RS-30199 and RS-64459 in binding and functional experiments are su




Psychopharmacology (Berl). 1998 Jul;138(2):198-206.
Dose-dependent influence of buspirone on the activities of selective serotonin reuptake inhibitors in the mouse forced swimming test.

Redrobe JP, Bourin M.

GIS Medicament, JE 2027 Neurobiologie de l'Anxiete, Faculte de Medecine, Nantes, France.

Recent clinical data suggest that buspirone may enhance the efficacy and/or reduce the latency to therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in unipolar major depressive disorder. The present study, using the mouse forced swimming test, was performed to investigate further the mechanisms involved in the potential antidepressant-enhancing effects of buspirone. Prior administration of buspirone (0.06 mg kg(-1), i.p.) significantly enhanced the anti-immobility effects of subactive doses of fluvoxamine (4 mg kg(-1), i.p.; P < 0.01), paroxetine (4 mg kg(-1), i.p.; P < 0.01), citalopram (4 mg kg(-1), i.p.; P < 0.01) and sertraline (2 mg kg(-1), i.p.; P < 0.01) in the forced swimming test. However, pretreatment with buspirone did not induce antidepressant-like effects when tested in combination with fluoxetine (4 mg kg(-1), i.p.). Each antidepressant tested reduced immobility time in the forced swimming test [citalopram (16 mg kg(-1), i.p.; P < 0.01), fluoxetine (32 mg kg(-1), i.p.; P < 0.01), fluvoxamine (32 mg kg(-1), i.p.; P < 0.01), paroxetine (16 mg kg(-1), i.p.; P < 0.01) and sertraline (16 mg kg(-1), i.p.; P < 0.01)]. Pretreatment with buspirone (0.5 mg kg(-1), i.p.), or its major metabolite 1-PP (0.5 mg kg(-1), i.p.), attenuated all SSRI-induced anti-immobility effects (P < 0.01). Concomitant studies of locomotor activity ruled out any stimulant or sedative effects of the interactions. The results of the present study suggested that low dose buspirone enhanced the activity of subactive doses of SSRIs in the mouse forced swimming test, probably via an action at 5-HT1A receptors. On the other hand, a high dose of buspirone attenuated the antidepressant-lik