ms.cc.ntu.edu.tw

The present study investigated the effect of buspirone on memory formation in an aversive learning task. Male Wistar rats were trained on the inhibitory avoidance task and tested for retention 1 day after training. They received peripheral or intra-amygdala administration of buspirone or other 5-HT1A drugs either before or after training. Results indicated that pretraining systemic injections of buspirone caused a dose-dependent retention deficit; 5. 0 mg/kg had a marked effect and 1.0 mg/kg had no effect. Post-training injections of the drug caused a time-dependent retention deficit, which was not due to a state-dependent effect on retrieval. When training in the inhibitory avoidance task was divided into a context-training phase and a shock-training phase, buspirone impaired retention only when administered in the shock-training phase, suggesting that the drug influenced memory processing of affective events. Further results indicated that post-training intra-amygdala infusion of buspirone or the 5-HT1A agonist 8-hydroxy-di-n-propylaminotetralin (8-OH-DPAT) caused a time-dependent and dose-dependent retention deficit. Post-training intra-amygdala infusion of the 5-HT1A antagonist WAY100635 (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)-N-(2-pyridyl) cyclohexane carboxamine maleate) attenuated the memory-impairing effects of buspirone. These findings suggest that buspirone may modulate memory storage processes in the inhibitory avoidance task through an action on amygdaloid 5-HT1A receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10215901&dopt=Abstract buspirone Buspar




Behav Pharmacol. 1991 Nov;2(4 And 5):369-378.
Modification of the discriminative stimulus effects of 8-OH-DPAT, buspirone and the beta-adrenoreceptor antagonist pindolol after chronic administration of the 5-HT(1A) agonist 8-OH-DPAT in the pigeon.

Zhang L, Barrett JE.

Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA.

The involvement of adrenoreceptor blocking drugs with the 5-HT(1A)-mediated discriminative stimulus was studied in pigeons trained to discriminate the 5-HT(1A) receptor agonist 8-OH-DPAT (0.3mg/kg) from saline. Cumulative dose-response curves were determined for 8-OH-DPAT, the beta-adrenergic antagonist pindolol, the alpha(1)-antagonist prazosin, as well as for the 5-HT(1A) agonist buspirone, before, during and after (8-OH-DPAT and pindolol) chronic administration of 8-OH-DPAT (3.0mg/kg/day for 6 weeks). The dose-response curves for 8-OH-DPAT and buspirone, which substituted for 8-OH-DPAT, were shifted to the left during chronic 8-OH-DPAT administration. Prazosin did not substitute for 8-OH-DPAT at any time throughout the course of the study. Pindolol did not substitute for 8-OH-DPAT before chronic administration, but did so during and after 8-OH-DPAT was administered chronically. Chronic administration of 8-OH-DPAT resulted in a heightened sensitivity not only to the 5-HT(1A) agonists 8-OH-DPAT and buspirone, but also to what appear to be partial agonist effects of pindolol. This approach represents a first step in the in vivo characterization of changes in 5-HT(1A) sensitivity after chronic administration of 8-OH-DPAT using the drug discrimination procedure. This method may provide a useful behavioral model with which to investigate the mechanisms of anxiolytic and antidepressant effects of 5-HT(1A) agonists and beta-adrenoceptor blocking drugs that only become apparent after 2 to 4 weeks of chronic administration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11224080&dopt=Abstract buspirone Buspar




Behav Pharmacol. 1991 Dec;2(6):481-489.
Effects of 8-OH-DPAT and buspirone in a passive avoidance test and in the elevated plus-maze test in rats.

Klint T.

Kabi Pharmacia Therapeutics, Box 839, S-201 80 Malmo, Sweden.

Benzodiazepines are generally reported to be active in tests based on punished responding and in procedures involving exploratory behaviour, but the effects of 5-HT drugs thus far reported are inconsistent. The effects of the two 5-HT(1A) agonists 8-OH-DPAT and buspirone were studied in a passive avoidance test and in an elevated plus-maze test. In the passive avoidance test 8-OH-DPAT and buspirone, as well as diazepam and chlordiazepoxide, were effective, while, in the elevated plus-maze test, the two benzodiazepines were active whereas buspirone and 8-OH-DPAT were not. Comparing the effects of the 5-HT(1A) agonists with the two benzodiazepines in the passive avoidance test it is suggested that this test can be predictive for drugs influencing anxiety. The elevated plus-maze test has many advantages, such as the absence of noxious stimuli, compared to punishment procedures, but since the 5-HT(1A) agonists do not act as anxiolytic compounds in this test, it is suggested that the test does not provide a suitable model of anxiety.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11224090&dopt=Abstract buspirone Buspar




Behav Pharmacol. 1991 Dec;2(6):491-496.
Effects of buspirone on antinociceptive and behaviourial responses to the elevated plus-maze in mice.

Lee C, Rodgers RJ.

Department of Psychology, University of Bradford, Bradford BD7 1DP, UK.

Brief exposure to an elevated plus-maze (EPM) induces antinociception in male mice, a reaction that is not blocked by opiate receptor manipulations but which is completely inhibited by the benzodiazepine receptor agonist, diazepam. The present study examined the effects of a non-benzodiazepine anxiolytic, buspirone, on EPM antinociception and behaviour. EPM antinociception was completely abolished by 10mg/kg buspirone but was largely unaffected by lower doses (0.1-1.0mg/kg) of the compound. Behaviourally, 1-10mg/kg buspirone produced changes indicative of anxiety reduction, although the high dose anxiolytic profile was at least partially compromised by a general reduction in behaviour. Data are discussed in relation to the proposal that anxiety may be a critical factor in non-opioid forms of adaptive pain inhibition.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11224091&dopt=Abstract buspirone Buspar




Behav Pharmacol. 1993 Jun;4(3):217-230.
Buspirone and lorazepam abuse liability in humans: behavioral effects, subjective effects and choice.

Troisi 2nd JR, Critchfield TS, Griffiths RR.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore MD 21224, USA.

This study compared behavioral and subjective effects of two anxiolytics, the benzodiazepine lorazepam and the azaspirodecanedione buspirone, in healthy male volunteers with histories of sedative drug abuse. Placebo, lorazepam (1, 2, 4, 8mg/70kg) and buspirone (15, 30, 60, 120mg/70kg) were administered p.o. in a mixed sequence in a double-blind, cross-over design. Lorazepam, but not buspirone, decreased psychomotor/cognitive performance. Both drugs produced similar increases in ratings of drug strength, however the onset and offset times for lorazepam were later than for buspirone. Lorazepam increased ratings of liking in contrast to buspirone which produced negative mood-related subjective effects (e.g. increases in ratings of disliking, bad/unpleasant effects, and tension-anxiety). Lorazepam was categorized by subjects as producing effects similar to barbiturates or benzodiazepines in contrast to buspirone which was not. When subjects were given a choice between self-administering an intermediate dose of lorazepam (4mg/70kg) or buspirone (60mg/70kg), which produced similar ratings of drug strength, eight out of nine subjects chose lorazepam. This study provides the clearest human experimental evidence to date that the abuse liability of buspirone is lower than that of a prototypic benzodiazepine, even at supratherapeutic doses.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11224189&dopt=Abstract buspirone Buspar




Behav Pharmacol. 1993 Jun;4(3):263-268.
Interactions of buspirone or gepirone with nicotine on schedule-controlled behavior of pigeons.

Nader MA, Hannemann M.

Department of Psychiatry, The University of Chicago, Chicago, IL 60637, USA.

The primary purpose of the present study was to examine the interaction of buspirone with nicotine in pigeons responding under a fixed-ratio 30 schedule of food presentation. The hypothesis was that the dopamine D2 receptor antagonist activity of buspirone would attenuate the rate-decreasing effects of nicotine. When administered alone, buspirone (0.3-10mg/kg) and (-)-nicotine (0.1-3.0mg/kg) decreased response rates in a dose-related manner, with ED(50) values (+/-95% C.L.) of 3.0 (1.7-5.1) mg/kg and 1.0 (0.7-1.5) mg/kg, respectively. Low doses of buspirone (0.3-1.0mg/kg) did not significantly shift the nicotine dose-response function, while doses of buspirone (3.0-10mg/kg) that produced rate-decreasing effects shifted the nicotine dose-response function to the left. There was no significant statistical interaction between buspirone and nicotine indicating that the shifts in the nicotine dose-response function were parallel. The buspirone analog gepirone (0.3-10mg/kg), which like buspirone is a serotonin (5-HT(1A)) agonist, but unlike buspirone is relatively devoid of D2 antagonist activity, was also tested in combination with nicotine. Gepirone was less potent in decreasing response rates compared with buspirone, with an ED(56) value of 4.5 (3.1-6.7) mg/kg. Rate-decreasing doses of gepirone (3.0-10mg/kg) in combination with nicotine resulted in parallel shifts to the left of the nicotine dose-response function. There was no statistically significant difference between the effects of buspirone and those of gepirone on the nicotine dose-response function. Isobolograms indicated that the pharmacological interactions between buspirone or gepirone and nicotine were not different from additivity. These results suggest that the combined effects of buspirone and nic




Behav Pharmacol. 1993 Oct;4(5):487-493.
Variable-ratio schedules of timeout from avoidance: effects of anxiolytic drugs.

Galizio M, Hale KL, Liborio MO, Miller M.

Department of Psychology, University of North Carolina at Wilmington, Wilmington, NC 28403, USA.

Concurrent performances in rats were studied under conditions where responses on one lever postponed shock on an unsignaled avoidance schedule, and responses on another level produced periods of signaled timeout from avoidance on a variable-ratio schedule. This procedure resulted in relatively high rates of responding on the timeout lever, and provided a baseline which permitted simultaneous evaluation of drug effects on two different types of negative reinforcement (shock postponement vs timeout). Chlordiazepoxide and ethanol selectively increased responding on the timeout lever at low doses, while higher doses decreased responding on both levers. Two 5-HT(1A) agonists, buspirone and 8-OH-DPAT, had different effects. Buspirone decreased responding across all effective doses, but 8-OH-DPAT increased responding on both the timeout and avoidance levers, with greater increases noted in responding maintained by timeout. These results replicate and extend previous findings, and support the notion that traditional anxiolytic drugs like chlordiazepoxide and ethanol may increase the reinforcing properties of escape from an avoidance schedule. Differences between the behavioral effects of buspirone and 8-OH-DPAT may reflect differential activity at the 5-HT(1A) receptor or the dopaminergic properties of buspirone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11224215&dopt=Abstract buspirone Buspar




J Neurochem. 1999 May;72(5):2022-31.
Effects of acute and chronic administration of the serotonin1A agonist buspirone on serotonin synthesis in the rat brain.

Okazawa H, Yamane F, Blier P, Diksic M.

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada.

The effects of acute and chronic administration of buspirone, a serotonin 5-HT1A agonist, on the 5-HT synthesis rates in various rat brain structures were investigated using alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) and an autoradiographic method. In the acute treatment study, buspirone (10 mg/kg) was injected subcutaneously 30 min before alpha-[14C]MTrp administration (30 microCi over 2 min) into a femoral vein. In the chronic treatment study, buspirone was given in a sustained fashion (10 mg/kg/day) for 14 days using an osmotic minipump implanted subcutaneously. Rats were killed 60 and 150 min after alpha-[14C]MTrp administration (two-time point method). A single dose of buspirone induced a significant decrease of 5-HT synthesis throughout the brain with the exception of the pineal body. However, the chronic treatment with buspirone did not induce significant differences in 5-HT synthesis in the brain. There was no significant difference in plasma free tryptophan concentration between any of the groups. The unaltered 5-HT synthesis rates in the chronic treatment study likely reflect a normalization of this parameter due to a desensitization of 5-HT1A autoreceptors on the cell body of 5-HT neurons, which has been previously shown to occur following long-term treatment with 5-HT1A agonists.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10217280&dopt=Abstract buspirone Buspar