Neuropharmacology. 1993 May;32(5):429-37.
Buspirone increases social investigation in pair-housed male mice; comparison with the effects of chlordiazepoxide.

Gao B, Cutler MG.

Department of Biological Sciences, Glasgow Caledonian University, U.K.

Effects of buspirone (1, 5 and 10 mg/kg, i.p.) on the behaviour of adult male CD1 mice have been compared with those of chlordiazepoxide (1, 4 and 8 mg/kg, i.p.). Commencing at 30 min after injection, the behaviour of each mouse was examined by ethological procedures during 5 min social encounters with an untreated partner in the animal's home cage and in the more aversive situation of an unfamiliar neutral cage. In both test environments, buspirone at 1 and 5 mg/kg and chlordiazepoxide (CDP) at 1 and 4 mg/kg increased social investigation and some of its constituent elements, while decreasing non-social activity and the element, "explore" (and for CDP, of "scanning" also). In both test environments, the increase of social investigation by buspirone and CDP was less marked at 10 and 8 mg/kg, respectively. For CDP, although not for buspirone, this effect was related to dose-dependent increases of immobility coupled with reductions of exploratory non-social activity and scanning below those occurring at the intermediate dose level. Buspirone at 5 mg/kg increased social investigation to a greater extent in the home cage (P < 0.01) than in the unfamiliar neutral cage (P < 0.05), whereas CDP was approximately equipotent in the two test situations. In the neutral cage, buspirone at all dose levels showed an additional effect of increasing the time spent by the mice in digging, whereas chlordiazepoxide dose-dependently increased aggression. These results indicate anxiolytic activity by both compounds after acute administration, and identify certain differences in the profile of their other effects on social behaviour.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8321425&dopt=Abstract buspirone Buspar




Pharmacol Toxicol. 1993 Jun;72(6):398-406.
Effects of 5-HT1A receptor agonists on patterns of rat motor activity in relation to effects on forebrain monoamine synthesis.

Ahlenius S, Hillegaart V, Salmi P, Wijkstrom A.

Department of Behavioral Pharmacology, Preclinical Research & Development Laboratories, Astra Arcus AB S-151, Sodertalje, Sweden.

The effects of the 5-HT1A receptor agonists 8-OH-DPAT (0.15-2.5 mumol kg-1 subcutaneously), flesinoxan (0.6-10.0 mumol kg-1 subcutaneously) and buspirone (1.9-30.0 mumol kg-1 subcutaneously) on spontaneous motor activity in male Sprague-Dawley rats was examined in a photocell-equipped open-field arena. Following motor activity observations, the cerebral aromatic L-amino acid decarboxylase inhibitor NSD-1015 (100 mg kg-1 intraperitoneally) was administered and 30 min. later the animals were decapitated for subsequent analysis of the accumulated forebrain DOPA and 5-HTP levels, as an estimate of the rate of monoamine synthesis. 8-OH-DPAT and flesinoxan produced a similar and characteristic pattern of changes of the spontaneous motor activity in normal animals i.e. a moderate decrease in locomotor activity, a marked suppression of rearing and an increase in the relative amount of forward locomotion and of activity in the periphery of the open-field arena. This behavioural profile was closely related to a decrease in forebrain 5-HTP accumulation, indicating 5-HT receptor stimulation. In agreement with these observations buspirone also produced an increase in peripheral activity and a suppression of rearing. In contrast to effects by 8-OH-DPAT and flesinoxan, however, buspirone produced a further reduction of locomotor activity and reduced the forward locomotion. This difference in behavioural profile between buspirone and the other two compounds is probably explained by its DA receptor blocking properties, as indicated by an increased DOPA accumulation in the neostriatum. At least partially, 8-OH-DPAT, flesinoxan and buspirone, all antagonized reserpin




Acta Psychiatr Scand. 1993 Jul;88(1):1-11.
The relative efficacy of high-dose buspirone and alprazolam in the treatment of panic disorder: a double-blind placebo-controlled study.

Sheehan DV, Raj AB, Harnett-Sheehan K, Soto S, Knapp E.

Institute for Research in Psychiatry, University of South Florida College of Medicine, Tampa.

This 8-week double-blind placebo-controlled trial investigated the relative efficacy and safety of alprazolam and buspirone in the treatment of panic disorder. Alprazolam (mean +/- SD dose 5.2 +/- 2.6 mg) produced a rapid and sustained improvement in panic attacks, anxiety, phobias, and disability and was superior to buspirone (mean +/- SD dose 61 +/- 26.5 mg) and placebo on all of these measures on completer (n = 85) and endpoint analysis (n = 92). Although higher doses of buspirone were used in this study than in previous trials, buspirone was not superior to placebo on any of the outcome measures. The results were disappointing in light of buspirone's benign side effect profile and low abuse potential.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8372689&dopt=Abstract buspirone Buspar




J Am Vet Med Assoc. 1993 Jul 15;203(2):254-8.
Effectiveness of buspirone on urine spraying and inappropriate urination in cats.

Hart BL, Eckstein RA, Powell KL, Dodman NH.

Department of Physiological Sciences, University of California, Davis 95616.

The most frequent type of behavior problem in cats for which veterinary consultation is sought is problem urination. Urine spraying and urine marking have been treated by use of long-acting progestins and diazepam, a benzodiazepine antianxiety drug. Effectiveness of the nonbenzodiazepine antianxiety drug, buspirone, in suppressing urine spraying and marking in 47 male and 15 female cats was evaluated. The effect of the drug in correcting inappropriate urination in 9 cats also was evaluated. Buspirone resulted in a favorable response (> 75% reduction) in 55% of cats treated for urine spraying or marking. There was no sex difference in effectiveness of the treatment, but cats from single-cat households responded favorably significantly (P < 0.001) less frequently than those from multiple-cat households. The 55% response rate was within the range of treatment effectiveness that has been reported for diazepam, and was greater than that reported for progestin. In contrast to diazepam, with which over 90% of treated cats resumed spraying or marking when the drug was gradually discontinued, only half of the cats treated with buspirone resumed spraying when the drug was discontinued after 2 months of treatment (P < 0.001). This difference between diazepam and buspirone in resumption of urine spraying was attributed to diazepam's induction of physiologic and behavioral dependency, not found with buspirone. Cats that resumed spraying were placed on long-term treatment ranging from 6 to 18 months. Buspirone also did not cause the adverse effects of sedation and ataxia, which commonly are seen with diazepam treatment. In cats treated for inappropriate urination, 56% returned to normal litter box usage.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8407484&dopt=Abstract




Life Sci. 1993;53(15):1217-25.
Effects on open-field behavior of diazepam and buspirone alone and in combination with chronic caffeine.

Hughes RN.

Department of Psychology, University of Canterbury, Christchurch, New Zealand.

Effects of diazepam (1, 2 mg/kg) and buspirone (1.25, 2.5 mg/kg) on locomotor and rearing activity were observed in rats tested in an open field. Both doses of each drug reduced ambulation. However, for buspirone, this effect was confined to females. Walking and rearing was reduced by the higher dose of diazepam and rearing by both doses of buspirone. In rats that had ingested approximately 26 mg/kg/day of chronic caffeine for seven days prior to and immediately before testing, all effects of diazepam observed earlier failed to achieve significance except for ambulation. However, all earlier buspirone effects (including female-only decreased ambulation) were unaffected by the caffeine treatment. It was concluded that buspirone may be preferable to diazepam as an anxiolytic when in the presence of regular caffeine ingestion.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8412479&dopt=Abstract buspirone Buspar




Proc Soc Exp Biol Med. 1993 Apr;202(4):447-50.
Prolactin-releasing effect of buspirone in developing and adult male and female rats.

Hockl PF, Diaz GS, Libertun C.

Laboratorio de Neuroendocrinologia, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.

The prolactin-releasing effects of buspirone, an azaspirodecanedione anxiolytic drug unrelated to the benzodiazepines in structure and pharmacologic properties, was examined in developing and adult male and female rats. The possibility that effects of this drug on hormone release could be modulated by neonatal brain sexual differentiation was also evaluated. A single injection of buspirone, 2 or 10 mg/kg body wt, increased serum prolactin (PRL) levels in both sexes; the increase was significant from Day 12 onward. The PRL-releasing effect increased with age. No significant sexual differences were observed in younger rats, but in peripubertal and adult animals, the hyperprolactinemic response was higher in the female. Neonatal androgenization of females or orchidectomy of males failed to modify the PRL-releasing action of buspirone. Serum titers of luteinizing hormone and follicle-stimulating hormone were not modified by buspirone at any age. The present results show for the first time the ontogeny of the PRL-releasing effect of buspirone in male and female rats, and provide evidence that the response is higher in the female and that the effect does not depend on brain sexual differentiation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8456109&dopt=Abstract buspirone Buspar




Brain Res Bull. 1993;30(5-6):547-50.
Buspirone-induced carbohydrate feeding is not influenced by route of administration and nutritional status.

Li ET, Luo S.

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.

Rats were habituated to ad lib food intake from two isoenergetic diets that differed in carbohydrate and protein content. To examine the route of administration effect, buspirone (0.6, 1.0, and 1.4 mg/kg) was injected into satiated rats either subcutaneously or intraperitoneally. Overall, no route of administration effect was observed; however, when results of the lowest dose were analyzed separately, the subcutaneous route was more effective than the intraperitoneal route. Regardless of route of administration, buspirone increased food intake over the first 2 h of food presentation in a dose-dependent manner. Moreover, the increase was entirely attributed to increases in intake from the high carbohydrate diet. In the subsequent experiment, the effect of buspirone (0.6 mg/kg) was examined in both satiated (early light period) and nonsatiated rats (early dark period). Both groups responded to buspirone with an increase in carbohydrate intake. Despite differences in baseline intake, the absolute increase was similar between satiated and nonsatiated rats. These data suggest that both sensitivity and selectively of buspirone-induced feeding are neither influenced by route of administration nor nutritional status of rats.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8457904&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1992 Sep;43(1):167-71.
Buspirone produces a dose-related impairment in spatial navigation.

McNaughton N, Morris RG.

Department of Psychology, University of Otago, Dunedin, New Zealand.

Classical anxiolytic drugs and hippocampal lesions have common behavioural effects that include loss of place navigation in the water maze. The novel anxiolytic drug buspirone, unlike classical anxiolytic drugs, does not interact with GABA and is not muscle relaxant, sedative, hypnotic, anticonvulsant, or addictive. Buspirone affects hippocampal electrophysiology in a similar fashion to classical anxiolytics and so we predicted it would have similar effects on spatial navigation. Rats injected with buspirone (0.1-10.0 mg/kg, IP) showed a loss of acquisition of spatial navigation in the water maze that has a similar dose dependence to that reported for the effects of buspirone on the hippocampus. This finding demonstrates that the effects of anxiolytics on spatial navigation are not due to their side effects and supports the view that changes in hippocampal function may underlie some components of clinical anxiolytic action.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1409800&dopt=Abstract buspirone Buspar