agrsci.dk

Behavioural and hypothalamic-pituitary-adrenal (HPA) axis responses were investigated in farm mink (Mustela vison) selected for either confident or fearful behaviour for nine generations.Two groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given the serotonin (5-HT) 1A receptor agonist buspirone (1.25 mg/kg/day), whereas two other groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given saline, continuously for 5 weeks via osmotic minipumps. Behavioural reactions towards a novel object and towards humans were tested after 19-25 days, and HPA axis reactivity [adrenocorticotropic hormone (ACTH), cortisol] was measured after 28-31 days of treatment. Confident mink were more exploratory than fearful mink towards humans and a novel object. Confident mink spent more time in contact with the object than did fearful mink during saline-but not during buspirone-treatment. buspirone increased approach-withdrawal conflict behaviour towards a object in fearful mink only. The chronic dose of buspirone did not reduce fear towards humans and did not affect latencies to reaction, number of contacts, number and duration of manipulations, and stereotypic behaviour in a Novel Object test. Different HPA axis responses have emerged between confident and fearful mink, together with a different degree of fear-related behaviour. Fearful mink have a higher cortisol combined with a lower ACTH secretion than confident mink in response to capture and blood sampling. The central serotonergic system may be involved, and even though the precise underlying mechanisms are presently unknown, treatment with a 5-HT

psych.uib.no

BACKGROUND: To what extent fibromyalgia belongs to affective spectrum disorders or anxiety spectrum disorders remains disputed. Buspirone induces a hypothermic response, which most likely is due to 5-HT(1A) autoreceptor stimulation, and growth hormone (GH) release, which probably is related to postsynaptic 5-HT(1A) receptor stimulation. The prolactin response to buspirone has been suggested to be mediated through dopamine (DA) antagonistic effects. OBJECTIVES: Based on the assumption that fibromyalgia is more strongly related to stress and anxiety than affective spectrum disorders, we hypothesized that compared to population controls, fibromyalgia patients should demonstrate an increased prolactin response (DA sensitivity) to buspirone challenge test, but no difference in hypothermic response or GH release (5HT sensitivity). METHOD: A 60-mg dose of buspirone was given orally to 22 premenopausal women with fibromyalgia and 14 age and sex matched healthy control subjects. Core body temperature, growth hormone and prolactin levels were analyzed at baseline and after 60, 90, and 150 min. RESULTS: Fibromyalgia patients showed an augmented prolactin response to buspirone compared to controls. Temperature and growth hormone responses did not differ from controls. CONCLUSIONS: Dopaminergic rather than serotonergic neurotransmission is altered in fibromyalgia, suggesting increased sensitivity or density of dopamine D(2) receptors in fibromyalgia patients. Stress and anxiety is an important modulator of dopaminergic neurotransmission. Our results suggest that fibromyalgia is related to anxiety and associated with disturbance in the stress resp




AAPS PharmSci. 2003;5(2):E14.
Iontophoretic transdermal delivery of buspirone hydrochloride in hairless mouse skin.

Al-Khalili M, Meidan VM, Michniak BB.

Department of Pharmaceutical Sciences, University of South Carolina, Columbia, SC 29208, USA.

The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm2 resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel resulted in a synergistic effect when combined with iontophoresis. Menthol was the most active enhancer, and when combined with iontophoresis it was possible to deliver 10 mg/cm2/day of buspirone hydrochloride.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12866941&dopt=Abstract buspirone Buspar

hotmail.com

OBJECTIVE: To study the role of different antidepressants on exploration, spontaneous motor activity and isolation-induced aggressiveness in mice, further to discuss different mechanisms of their anti-aggression. METHODS: With an aggressive model induced by isolation housing in mice, antagonism of different antidepressants against isolation-induced aggression was evaluated. In the group-housed mice given the same treatment as aggressive test, exploration and spontaneous motor activity were measured. RESULTS: (1) Mianserin (0.5-5 mg/kg-1), buspirone (2.5-10 mg.kg-1) and meclobemide (2.5-10 mg.kg-1) significantly inhibited the exploration in the group-housed mice, but not fluoxetine (2.5-10 mg.kg-1), imipramine (2.5-10 mg.kg-1) and DOI (0.5-2 mg.kg-1); (2) Both mianserin and buspirone, but not fluoxetine, imipramine, meclobemide and DOI, obviously reduced spontaneous motor activity; (3) Fluoxetine, miaserin, imipramine and buspirone significantly and dose-dependently antagonized isolation-induced aggressive behavior, whereas meclobemide failed to attenuate aggression. DOI dual-regulated aggressiveness in isolation mice. CONCLUSION: Our findings suggest that the effects of fluoxetine, mianserin, buspirone, imipramine, meclobemide and DOI on exploration, spontaneous motor activity and isolation-induced aggression in mice are different, which may involve different pharmacological mechanisms underlying their anti-aggression in isolation mice. 5-HT1A and 5-HT2A/2C receptors may mediate isolation-induced aggressive behavior in mice. The involvement of 5-HT receptor subtypes needs further clarification.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12920810&dopt=Abstract buspirone Buspar




J Pharm Pharmacol. 1999 May;51(5):601-7.
Pharmacokinetics of buspirone following oral administration to rhesus monkeys.

Marathe PH, Shen F, Markham P, Greene DS.

Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Princeton, NJ 08540, USA.

Pharmacokinetics of buspirone and its active metabolite, 1-pyrimidinyl piperazine (1-PP) following oral administration were assessed in rhesus monkeys at doses used in chronic toxicology studies. The study was conducted over four periods in three male and three female rhesus monkeys. In the first three periods, buspirone hydrochloride solution was administered in a randomized manner by oral gavage at doses (expressed as buspirone free base) of 12.5, 25 and 50 mg kg(-1) once a day on days 1 and 7 and twice a day on days 2-6. In the last period, all monkeys received 25 mg kg(-1) buspirone as a single daily dose for 7 days. Serial plasma samples were collected for analysis of buspirone and 1-PP on days 1 and 7 in the first three periods and on day 7 in the last period for assessment of single dose and steady-state pharmacokinetics. Inter-animal variability in the pharmacokinetics of buspirone was high. Examination of Cmin vs time plots revealed that the steady state was attained by day 7 except for one monkey who demonstrated much higher Cmin values. For buspirone, dose proportionality was concluded for both Cmax and AUC on day 1 but not on day 7. The accumulation factor on day 7 for buspirone was nearly 5 for Cmax and 7 for AUC when compared with day 1. For 1-PP, dose proportionality was concluded except for Cmax in male monkeys on day 7. In contrast to buspirone, 1-PP showed less than 2-fold accumulation in Cmax and AUC values on day 7 compared with those on day 1. Exposure at a dose of 25 mg kg(-1) once daily was in between the 125 mg kg(-1) and 25 mg kg(-1) twice-a-day regimens. These results document dose-dependency in the steady-state pharmacokinetics of buspirone in rhesus monkeys.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10411220&dopt=Abstract buspirone Buspar




Eur J Pharmacol. 2003 Sep 23;477(3):205-11.
Buspirone differentially modifies short-term memory function in a combined delayed matching/non-matching to position task.

Pache DM, Fernandez-Perez S, Sewell RD.

Neuropharmacology, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cathays Park, Wales CF10 3XF, Cardiff, UK.

This study investigated the action of 5-hydroxytryptamine (5-HT) mimetics on short-term memory function. The objective was to determine whether two closely related tasks could differentiate between partial 5-HT(1A) receptor activation, full 5-HT(1A) receptor activation and generalised enhanced serotonin (5-HT) activity. Male hooded Lister rats were trained to perform an operant-based combined delayed matching/non-matching to position task. Drugs used were: fluoxetine (3 mg/kg, i.p.), a selective 5-HT reuptake inhibitor; the full 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.3 mg/kg, s.c.); and the partial 5-HT(1A) receptor agonist, buspirone (1 mg/kg, i.p.). Buspirone differentially disrupted response accuracy depending on the style of trial. There was no such difference in the case of 8-OH-DPAT, which impaired accuracy in both delayed matching/non-matching to position task, while fluoxetine affected neither. Thus, the findings suggest that partial 5-HT(1A) receptor activation compromises cognitive function to a greater extent than full 5-HT(1A) receptor activation, although a dopaminergic component cannot be excluded since buspirone possesses some dopamine D2 receptor antagonist activity. Furthermore, it suggests that there is a differential role for 5-HT in these two closely related behavioural tasks.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14522358&dopt=Abstract buspirone Buspar




Eksp Klin Farmakol. 2003 Jul-Aug;66(4):12-6.
[Effect of buspirone on aggressive and anxiety behavior of male mice with various aggressive experience]

[Article in Russian]

Bondar' NP, Kudriavtseva NN.

Department of Neurogenetics of Social Behavior, Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences, pr. akad. Lavrent'eva, 10, Novosibirsk, 630090 Russia.

The effect of the 5-HT1A receptor agonist buspirone on the aggressive and anxious behavior of C57BL/6J male mice with different experience of aggression was studied. In the group of animals with short-time (3 days) winner experience, buspirone (1 mg/kg, i.p.) produced an anxiogenic effect (manifested in the plus-maze test) and reduced the level of aggression (agonist confrontation test). No such effects were observed in the group of animals with a long-time (20 days) aggression experience. It is suggested that the antiaggressive effect of buspirone in the former case is related to the anxiogenic action, while a long experience of aggression reduced the pharmacological sensitivity of 5-HT1A receptors to buspirone in the latter case.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14558344&dopt=Abstract buspirone Buspar

utu.fi

RATIONALE: Preliminary in vitro findings indicated that the novel anxiolytic drug, deramciclane is a substrate for the cytochrome P(450) (CYP) 3A4 isoenzyme. Moreover, its co-administration with buspirone, another anxiolytic drug, is likely in clinical practice. OBJECTIVES: The primary objective of the present study was to evaluate the in vivo effects of deramciclane on CYP3A4 activity as measured by buspirone pharmacokinetics. The secondary objective was to study the possible pharmacodynamic interaction between these two anxiolytic drugs. METHODS: Sixteen healthy subjects received 60 mg deramciclane or matched placebo for 8 days in this randomized, double-blind, cross-over study. On day 8 of both phases, the subjects received a 20-mg single dose of buspirone. Buspirone and its active metabolite, 1-pyrimidylpiperazine (1-PP), concentrations were measured for 24 h. Pharmacodynamic testing and measurement of plasma prolactin concentrations were carried out on day 7 and day 8 to assess the pharmacodynamic consequences of deramciclane and buspirone co-administration. RESULTS: Repeated administration of deramciclane had no effect on CYP3A4 activity as measured by buspirone pharmacokinetics. However, deramciclane administration caused an inhibition of the further, not CYP3A4-dependent, metabolism of 1-PP as evidenced by 84% increase in the AUC ( P<0.001) and 20% increase in the elimination half-life ( P=0.0012) of 1-PP. Deramciclane did not potentiate the buspirone-induced increase in prolactin secretion. No significant differences were found in the psychomotoric testing or the subjective max