Eur J Pharmacol. 1987 Apr 7;136(1):123-7.
Effect of buspirone on single unit activity in locus coeruleus and dorsal raphe nucleus in behaving cats.

Wilkinson LO, Abercrombie ED, Rasmussen K, Jacobs BL.

The effects of administration of the non-benzodiazepine anxiolytic buspirone on the spontaneous and sensory evoked single unit activity of serotonergic (5-HT) neurons in the dorsal raphe nucleus and noradrenergic (NE) neurons in the locus coeruleus were examined in freely moving cats. Buspirone (1.0 mg/kg i.p.) strongly suppressed both the spontaneous and evoked activity of 5-HT dorsal raphe nucleus neurons. The spontaneous activity of NE neurons in the locus coeruleus was non-significantly increased by drug administration, while the evoked response was unaffected. These effects occurred during a period of mild behavioral activation. It is suggested that the anxiolytic effects of buspirone administration are not achieved through an action of NE neurons, but may be mediated in part by actions on 5-HT neurons in the dorsal raphe.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3595712&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1987 May;27(1):171-5.
Buspirone effects in an animal conflict procedure: comparison with diazepam and phenobarbital.

McCloskey TC, Paul BK, Commissaris RL.

Buspirone has been introduced as a novel non-benzodiazepine anti-anxiety agent. The Conditioned Suppression of Drinking (CSD) paradigm is an "animal model" for anxiety which provides information on both the relative potency and relative efficacy of anti-conflict agents. The present study compared the anti-conflict effects of buspirone to those of more "classical" anti-anxiety agents, diazepam and phenobarbital. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.5 mA), electrification being signalled by a tone. Within 2-3 weeks control CSD responding had stabilized (approximately 15-20 shocks/session and 10-15 ml water/session); drug tests were conducted at weekly intervals. Diazepam and phenobarbital markedly (400-500%) increased the number of shocks received at doses which did not depress background responding (i.e., water intake). A number of agents, most notably morphine and ethanol, did not reliably affect punished responding in the CSD. Administered IP, low doses (0.25-1 mg/kg) of buspirone increased punished responding only slightly (less than 100% increase); higher doses (2, 4 mg/kg) depressed background responding. Administered SC, buspirone (0.125-1.0 mg/kg) had more potent effects on both punished and unpunished responding; again, anti-conflict efficacy was only marginal. These results suggest that buspirone might be less effective than the benzodiazepines in the management of anxiety.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3615539&dopt=Abstract buspirone Buspar




Aviat Space Environ Med. 1987 Oct;58(10):989-91.
Buspirone blocks motion sickness and xylazine-induced emesis in the cat.

Lucot JB, Crampton GH.

Department of Pharmacology and Toxicology, Wright State University, Dayton, Ohio 45435.

Cats were tested for motion sickness following s.c. pretreatment with four doses of buspirone. Buspirone blocked motion sickness with an ED50 of 0.46 mg . kg-1 base. Buspirone pretreatment (4.0 mg . kg-1 base) also significantly blocked vomiting in cats later injected with 0.66 mg . kg-1 (base) s.c. of the emetic drug xylazine. The results are interpreted as showing that buspirone is acting at the vomiting center, the point of convergence for the separate mechanisms subserving chemically-induced emesis and motion sickness.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3675471&dopt=Abstract buspirone Buspar




Br J Clin Pharmacol. 1987 Oct;24(4):547-50.
Buspirone pharmacokinetics in patients with cirrhosis.

Dalhoff K, Poulsen HE, Garred P, Placchi M, Gammans RE, Mayol RF, Pfeffer M.

Department of Medicine A, Rigshospitalet, Copenhagen, Denmark.

The pharmacokinetics of a single oral dose of buspirone (20 mg) were determined in 12 patients with cirrhosis and 12 normal subjects. The mean AUC of buspirone was 55 +/- 38 s.d. ng ml-1 h in cirrhotics and 3.5 +/- 2.4 s.d. ng ml-1 h in normals. The time until maximum concentration (tmax) attained was similar in the two groups (0.6 vs 0.7 h), but mean maximum concentration Cmax was higher in patients (18.8 +/- 16.3 s.d. ng ml-1) than in normals (1.2 +/- 0.8 s.d. ng ml-1). Mean elimination half-life of buspirone was greater in cirrhotics, but this difference was marginally significant statistically (cirrhotics, 6.1 +/- 3.5 s.d. h, normals 3.2 +/- 1.5 s.d. h, P = 0.05). Eight of 12 patients and seven of 12 normal subjects had a second peak in the plasma concentrations of buspirone. In patients this occurred at 10.8 +/- 7.4 s.d. h after the dose, and its mean concentration was 3.1 +/- 6.6 ng ml-1. In normal subjects the second peak occurred at 4.3 +/- 2.1 h after the dose and its mean concentration was 0.5 +/- 0.3 ng ml-1. On the kinetic evidence buspirone should be used with caution in liver disease.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3689635&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1986 Aug;25(2):457-62.
Effect of the anxiolytic drug buspirone on prolactin and corticosterone secretion in stressed and unstressed rats.

Urban JH, Van de Kar LD, Lorens SA, Bethea CL.

Buspirone is an atypical anxiolytic drug that exerts its action at a receptor site other than the GABA-benzodiazepine-chloride ionophore complex. The present study examined the effect of buspirone on plasma prolactin and corticosterone levels in both control and stressed rats. In unstressed rats, buspirone produced dose-dependent increases in plasma prolactin and corticosterone levels. The minimal doses of buspirone which led to significant elevations in plasma prolactin and corticosterone levels were 1.0 and 2.0 mg/kg (IP), respectively. The effect of buspirone on both hormones was maximal 30 minutes after injection. The plasma levels of prolactin and corticosterone were significantly elevated in rats that were stressed using a conditioned fear paradigm. Buspirone produced a dose-dependent attenuation of the stress-induced increase in prolactin secretion. The stress-induced increase in corticosterone secretion was inhibited by the 0.5 mg/kg (IP) dose but not by the 2.0 mg/kg (IP) dose of buspirone, which increased corticosterone secretion both in stressed and unstressed rats. These data suggest that the effect of buspirone on plasma prolactin and corticosterone levels may be mediated by two different mechanisms of action.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3763667&dopt=Abstract buspirone Buspar




J Pharmacol Exp Ther. 1987 Feb;240(2):364-9.
Discriminative stimulus properties of buspirone in the pigeon.

Mansbach RS, Barrett JE.

The novel anxiolytic buspirone was administered to pigeons in a two-key drug discrimination task in an effort to characterize the stimulus properties of the drug and thereby aid in isolating the pharmacologic basis for its anticonflict effect. Key pecking was maintained by a schedule of reinforcement in which every 30th injection-appropriate response was reinforced by the presentation of food. Subjects were first trained to discriminate buspirone (1.0 mg/kg) from saline, and then generalization tests were conducted using a cumulative dosing procedure. Cumulative doses of buspirone (1.0-3.0 mg/kg), the buspirone analog MJ 13805 (1.0 mg/kg) and the 5-hydroxytryptamine-1A ligand 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.3-1.0 mg/kg) produced in excess of 90% buspirone-appropriate responding, whereas midazolam (0.03-1.0 mg/kg), haloperidol (0.03-1.7 mg/kg), apomorphine (0.03-1.0 mg/kg), clozapine (0.1-3.0 mg/kg), methysergide (0.1-3.0 mg/kg) and the 5-hydroxytryptamine-1B ligand 1-[3-chlorophenyl]piperazine (0.3-10.0 mg/kg) produced little or no buspirone-appropriate responding up to those doses that markedly decreased response rate. These findings support recent behavioral and receptor binding studies suggesting that serotonin receptors, and 5-hydroxytryptamine-1A receptors in particular, may be responsible for mediating the anticonflict effects of buspirone and other atypical anxiolytics. The results also corroborate other behavioral work showing that the anxiolytic effects of buspirone are most likely not mediated by the dopaminergic system.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3806400&dopt=Abstract buspirone Buspar




Alcohol. 1987 Jan-Feb;4(1):49-56.
Buspirone attenuates volitional alcohol intake in the chronically drinking monkey.

Collins DM, Myers RD.

Four macaque monkeys which showed excessive preference for ethyl alcohol solutions in a self-selection paradigm were used as subjects. Earlier these animals had been given intracerebroventricular (ICV) injections of human cerebrospinal fluid, which produced pharmacologically significant effects on the animals' alcohol consumption. The purpose of the present investigation was to determine whether the parenteral administration of a new anxiolytic compound, buspirone, would alter the pattern of alcohol drinking already established in the monkey. Initially the maximally selected concentration of alcohol of 12% was determined on the basis of a standard ad lib alcohol-water preference screen. Each monkey was offered 12% alcohol and water for a basal pre-injection period of 4 days. Then, on each of the next three days, either the saline control vehicle or buspirone, 1.25, 5.0 or 20.0 mg/kg, was injected intramuscularly at 930 and 1630 hours. On these days, behavioral observations were recorded before and after buspirone's administration in order to evaluate the latency as well as recovery from the drug's effect. Subsequently, a four-day post-injection, 12% alcohol-water test was conducted. Although the saline control and 1.25 mg/kg dose of buspirone were without effect on alcohol intake, both the 5.0 and 20.0 mg/kg doses of buspirone attenuated significantly the consumption of alcohol by the monkeys. This reduction in terms of absolute g/kg as well as the proportion of alcohol to water ingested was approximately 30-60% of baseline intakes. Following buspirone treatment, the amount of alcohol consumed returned essentially to previously high levels.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3828064&dopt=Abstract buspirone Buspar




Am J Med. 1986 Mar 31;80(3B):36-40.
Neuroendocrine effects of buspirone in patients with generalized anxiety disorder.

Cohn JB, Wilcox CS, Meltzer HY.

This study investigated a therapeutic regimen of buspirone, a new anxioselective drug, in patients with generalized anxiety disorder. The single-blind study, conducted in 23 outpatients, consisted of 28 days of buspirone treatment followed by four days of placebo treatment. Patients received a single 10-mg dose of buspirone on study day one, which was titrated to 10 mg three times daily by study day seven and which remained at 10 mg three times daily through study day 28. Blood samples were drawn on days one, 14, 28, and 32 for determination of plasma levels of prolactin, growth hormone, and cortisol. The therapeutic effect of buspirone was assessed by standard psychometric rating scales. When titrated to a total daily dose of 30 mg per day (10 mg three times daily), buspirone provided effective antianxiety therapy and had no significant effect on plasma levels of prolactin, growth hormone, or cortisol.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3963033&dopt=Abstract buspirone Buspar