Pharmacol Biochem Behav. 2000 Jul;66(3):645-51.
Effects of buspirone, diazepam, and zolpidem on open field behavior, and brain [3H]muscimol binding after buspirone pretreatment.

Siemiatkowski M, Sienkiewicz-Jarosz H, Czlonkowska AI, Bidzinski A, Plaznik A.

Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Sobieskiego 1/9, 02-957, Warsaw, Poland.

The effects of 5-HT(1A) receptor agonist buspirone, a nonselective (diazepam), and a selective (zolpidem) GABA(A) receptor agonist were compared in the open field test of neophobia. Unhabituated rats were pretreated with the drugs once, prior to a first exposure to the open field, and their behavior was recorded both during this test and during a second trial 24 h later. It has been hypothesized that the decrease in exploratory activity observed during the second test session may be considered an adaptive reaction to the first day aversive experience (neophobia). If so, a selective modulation of 5-HT and GABA systems activity during the test could bring about significant changes in animal behavior on the retest. Buspirone at the lowest dose of 0.3 mg/kg revealed anxiolytic-like properties on the first day, whereas the action of diazepam and zolpidem was modulated by the dose-related sedative effect. At the dose of 2.4 mg/kg buspirone elicited delayed in time anxiolytic-like action, i.e., produced the antithigmotactic effect during the retrial 24 h later. Diazepam and zolpidem failed to exhibit similar profile of action. Autoradiography of [3H]muscimol binding after pretreatment of rats with buspirone showed a significant increase in the selective radioligand binding within the frontal cortex and a similar, near-significant tendency in the dentate gyrus of the hippocampus. The behavioral data validate buspirone as important drug for the treatment of anxiety disorders, devoid of disruptive influence on motor and cognitive processes. The open field test, as modified by us, appeared sensitive in distinguishi




Brain Res. 1999 Mar 13;821(2):414-25.
Modification of sexual behavior of Long-Evans male rats by drugs acting on the 5-HT1A receptor.

Rehman J, Kaynan A, Christ G, Valcic M, Maayani S, Melman A.

Department of Urology, Albert Einstein College of Medicine/Montefiore Medical Center, 210th Street, Bronx, New York, NY 10467, USA.

Modulation of the sexual behavior of male rats by the anxiolytic buspirone (S-20499) and its analog gepirone were compared to the effects of 8-OH-DPAT (or DPAT, a selective 5-HT1A reference agonist), and BMY-7378 (a selective 5-HT1A partial agonist). Long-Evans rats were used; modulation of copulatory behavior and alteration of penile reflexes were examined. Modulation of copulatory behavior was assessed by three indices: frequency and length of intromission, and latency of ejaculation. DPAT, at doses of 1-8 mg/kg, reduced these three indices in a time dependent manner such that the effects peaked at 45 min and normalized at 90 min. The dose-effect relationship (assessed 45 min after DPAT injection) is bell-shaped with an ED50 approximately 1 mg/kg on the ascending limb of the curve. The effects of buspirone (2 mg/kg) and gepirone (2 mg/kg) on copulatory behavior were indistinguishable from control. BMY-7378 alone and in combination with these other 5-HT1A agonists reduced copulatory behavior, though not statistically significant. Penile reflexes, including number of erections, cups and flips, were inhibited by these agents: DPAT>buspirone>gepirone (inactive at 2 mg/kg). Furthermore, the latency period to erection was at least doubled by DPAT (2 mg/kg). Buspirone and gepirone, however, reduced the latency period to erection. BMY-7378 inhibited penile reflexes when administered alone and even more in combination with DPAT or buspirone. Two butyrophenone analogs, spiperone (a 5-HT1A and dopamine D2 antagonist) and haloperidol (a D2 antagonist), were also tested for their interaction with DPAT. Both of these drugs (at 0.25 mg/kg, 60 min after administration) reduce

koki.hu

Serotonergic anxiolytics yield contradictory results both in the laboratory and clinically. In an attempt to investigate the cause of discrepancies, the anxiolytic effect of buspirone (0, 3 or 10 mg/kg, single treatment) was tested 1 h and 4 h after injection in rats in different housing conditions. At 1 h after drug administration, buspirone increased corticosterone production and decreased locomotor behaviour in both the elevated plus-maze and the social interaction tests. No anxiolytic-like effect was produced in either test. At 4 h after drug injection, no corticosterone or locomotor effects of buspirone were observed. In contrast, anxiolytic effects emerged in this phase. Open arm exploration and social investigation were increased in the plus-maze and social interaction test, respectively. In the plus-maze, the anxiolytic effect was significant in isolated animals only. In the social interaction test, the anxiolytic effect was stronger in isolated than in group-housed animals. When corticosterone secretion was inhibited by adrenalectomy, a full anxiolytic effect of buspirone was observed 1 h after drug administration. It appears that the side effects of buspirone have a shorter duration than the main anxiolytic effect. The buspirone-induced increase in corticosterone may have abolished the anxiolytic effects of the drug shortly after injection. Individual housing enhanced the anxiolytic efficacy of buspirone 4 h after administration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11103892&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 2000 Sep;67(1):45-53.
The influence of buspirone, and its metabolite 1-PP, on the activity of paroxetine in the mouse light/dark paradigm and four plates test.

Hascoet M, Bourin M, Nic Dhonnchadha BA.

Faculty of Medicine and GIS Medicament, JE 2029 Neurobiologie de l'anxiete, Faculte de Medecine BP 53508, 1 rue Gaston Veil, 44035, Nantes, France.

Although numerous animal procedures have been employed in the study of antidepressants (ADs) in anxiety, the results following acute administration remain highly variable. The present study investigated the effect of the SSRI paroxetine (4, 8, and 16 mg/kg, IP) in two tests of anxiety in mice: the light/dark test paradigm, and the four plates test (FPT). In both tests, it was found that paroxetine resulted in an anxiolytic-like effect at doses that did not modify motor performance (at the doses of 4 and 8 mg/kg in the light/dark test and at the doses of 4, 8, and 16 mg/kg in the four plates test). In the light/dark paradigm, both doses of buspirone significantly potentiated paroxetine, while in the four plates only one dose of buspirone (a 5HT(1A) partial agonist) (0.06 mg/kg) increased the anxiolytic-like effect of paroxetine. Prior administration of 1-PP was without effect in the light/dark paradigm but antagonized the effect of paroxetine (at the dose of 0.06 and 0. 5 mg/kg) in the FPT. The results suggested that a balance between pre- and postsynaptic 5-HT(1A) receptor was implicated in the anxiolytic-like effect of paroxetine. Buspirone seemed to emphasize the role of paroxetine in 5-HT(1A) receptor modulation and exerted a biphasic influence in the two tests.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11113483&dopt=Abstract buspirone Buspar




Behav Pharmacol. 1989;1(1):57-67.
Further characterization of the discriminative stimulus effects of buspirone using monoamine agonists and antagonists in the pigeon.

Nader MA, Hoffmann S, Gleeson S, Barrett JE.

Department of Psychiatry, Box 411, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA.

White Carneau pigeons were trained to discriminate 1.0 mg/kg buspirone from saline when key pecking was maintained under a fixed-ratio 30 schedule of food presentation. Buspirone (0.3-10.0 mg/kg), the serotonin 1A (5-HT(1A)) agonist 8-OH-DPAT (0.1-1mg/kg), the buspirone analog BMY 7378 (3.0-5.6mg/kg), the mixed 5-HT(1A/1B) agonist RU 24969 (3.0-10.0mg/kg) and the 5-HT(1A) agonist spiroxatrine (0.1-1.0mg/kg) occasioned at least 80% buspirone-appropriate responding in all subjects tested. Administration of the 5-HT(1B) agonist (TFMPP 0.1-10.0mg/kg) or the 5-HT(3) antagonist (MDL 72222 (3.0-17.0mg/kg) resulted in primarily saline-key responding. The dopamine receptor antagonist chlorpromazine (1.0-17.0mg/kg), the specific D-2 receptor antagonist eticlopride (0.03-0.56mg/kg), the noradrenergic alpha-2 antagonist yohimbine (0.1-1.0mg/kg), the alpha-2 agonist clonidine (0.003-0.10mg/kg) and (+/-) and (-) propranolol (3.0-30.0mg/kg) all produced primarily saline-appropriate responding. Coadministration of the beta-adrenergic agonist isoproterenol (1.0-5.6mg/kg) or the 5-HT(1A) partial agonist BMY 7378 (0.01-10.0mg/kg) with 1.0mg/kg buspirone did not block the discriminative stimulus effects of buspirone. However, 3.0-10.0mg/kg BMY 7378, in combination with a lower dose of buspirone (0.3mg/kg) decreased drug-key responding to approximately 50%. Results from the present study suggest that (1) the discriminative stimulus effects of buspirone, 8-OH-DPAT, BMY 7378, RU 24969 and spiroxatrine are mediated through the 5-HT(1A) receptor; (2) buspirone's discriminative stimulus effects do not interact with the noradrenergic or dopaminergic system; and 3) under this procedure




Behav Pharmacol. 1989;1(2):153-160.
Buspirone, gepirone and ipsapirone disrupt both active and passive avoidance responding in rats.

Sanger DJ, Joly D, LePichon M.

Synthelabo Recherche (L.E.R.S.), 31, avenue P.V. Couturier, 92220 Bagneux, France.

The anxiolytic drug buspirone and its structural analogues gepirone and ipsapirone produce behavioural effects which differ from those seen with benzodiazepines and barbiturates. Buspirone has been reported to disrupt active avoidance responding without interfering with the ability to escape the aversive stimuli, an effect usually associated with antipsychotic drugs. In the present study, buspirone, gepirone and ipsapirone produced dose-related decreases in one-way, active avoidance responding of rats. However, these drugs did not consistently give rise to a within-session decline in avoidance responding as was seen with the dopamine antagonist metoclopramide. In a second experiment, buspirone, gepirone and ipsapirone disrupted the performance of a passive avoidance response. Rats previously conditioned to remain on a raised platform to avoid shock stepped off the platform after injection of these drugs. A similar effect on the passive avoidance response was not produced by chlordiazepoxide; diazepam, CL 218, 872, haloperidol, imipramine or d-amphetamine. These disruptions of the performance of both active and passive avoidance indicate a unique pharmacological profile for buspirone and similar drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11175398&dopt=Abstract buspirone Buspar




J Physiol Pharmacol. 2000 Dec;51(4 Pt 2):833-46.
5-HT1A receptor agonists buspirone and gepirone attenuate apomorphine-induced aggressive behaviour in adult male Wistar rats.

Pruus K, Skrebuhhova-Malmros T, Rudissaar R, Matto V, Allikmets L.

Department of Pharmacology, University of Tartu, Estonia.

We have studied the effects of acute serotonin (5-HT) 5-HT1A receptor agonist buspirone (0.5, 1.0, 2.5 and 5.0 mg/kg, s.c.), gepirone (5.0 and 10 mg/kg, s.c.), and 8-OH-DPAT (0.1, 0.25, and 0.5 mg/kg, i.p.) treatment on the apomorphine-induced aggressive behaviour in adult male Wistar rats. Buspirone in doses of 2.5 and 5.0 mg/kg completely blocked, gepirone (10 mg/kg) significantly attenuated the aggressiveness, and 8-OH-DPAT abolished aggressive behaviour only in the lowest dose used (0.1 mg/kg) which effect disappeared in higher doses. The antiaggressive effect of buspirone (2.5 mg/kg) and gepirone (10 mg/kg) was not reversed by a 5-HT1A receptor antagonist WAY 100635 (0.3 mg/kg). All 5-HT1A receptor agonists tested dose-dependently decreased the exploratory behaviour of experimentally naive rats, while buspirone (2.5 mg/kg) and gepirone (10 mg/kg) had only a weak effect on the locomotor activity and stereotyped behaviour in the apomorphine-pre-sensitised rats. In conclusion, our experiments demonstrate the 5-HTIA receptors may be involved in the mediation of the apomorphine-induced aggressive behaviour in adult male Wistar rats. However, the prominent antiaggressive effect of buspirone, and to a lesser extent--gepirone, seems to be mediated by some other mechanisms, evidently via the dopamine D2 receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11220492&dopt=Abstract buspirone Buspar




Behav Pharmacol. 1991 Feb;2(1):3-14.
Discriminative stimulus effects of the novel anxiolytic buspirone.

Ator NA.

The Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, 720 Rutland Avenue, Room 621, Baltimore, Maryland 21205, USA.

Separate groups of Long-Evans rats were trained to discriminate either 0.56 or 1.0mg/kg buspirone i.p. in a two-lever, drug vs no-drug discrimination procedure. Training took twice as long for the lower versus the higher training-dose group. Generalization tests were conducted with buspirone (0.1-1.8mg/kg, i.p., 0.32-10mg/kg, p.o.), pentylenetetrazole (1-18mg/kg, i.p.), meprobamate (3.2-180mg/kg, p.o.), haloperidol (0.01-0.32mg/kg, i.p.), and 8-OH-DPAT (0.01-0.32mg/kg, i.p.). Buspirone p.o. was 0.5-1.0 log(10) units less potent than buspirone i.p. in producing dose-dependent generalization (i.e. > 80% buspirone-lever responding). Dose-effect functions for the 1.0 training-dose group were to the right of those for the 0.56 group. Partial generalization to meprobamate occurred in both groups, representing the first report of overlap of the buspirone discriminative stimulus with that of another anxiolytic. Complete generalization to 8-OH-DPAT occurred, consistent with buspirone's prominent 5HT(1A)-receptor activity and replicating findings in the pigeon. Partial generalization to haloperidol was concluded: every rat generalized to haloperidol, but the gradients did not increase monotonically and drug-lever responding at a given dose was inconsistent within and across rats. The haloperidol results suggest a stronger influence of the dopaminergic component in the buspirone discriminative stimulus in rats than was found with pigeons. Although a previous study found generalization to buspirone from pentylenetetrazole in baboons, there was no generalization to pentylenetetrazole from buspirone in the present study.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11224042&dopt=Abstract buspirone Buspar