Behavioral Effects of Flibanserin (BIMT 17)

Borsini, Franco; Brambilla, Alessandro; Grippa, Nicoletta; Pitsikas, Nikolaos

doi:10.1016/s0091-3057(99)00072-6

Cited by 18 publications

(21 citation statements)

References 62 publications

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“…Flibanserin doses of 1–10 mg/kg IP produced a dose-and time-dependent depression of ICSS in this study, and these findings agree with previous reports that flibanserin displays similar potency to decrease rates of various other behaviors in rodents [6, 44]. For example, flibanserin doses of 8–16 mg/kg (IP) or 45 mg/kg (PO), which produced similar plasma flibanserin levels, decreased measures of spontaneous locomotion in female and male rats [6, 44].…”

Section: Discussionsupporting

confidence: 93%

“…The present results are not likely to reflect evaluation of an inadequate flibanserin dose range, because flibanserin was tested across a 10-fold dose range from low doses that produced no effect to high doses that only depressed ICSS, and flibanserin doses tested here also produce a range of other behavioral effects in rats (e.g. [43, 44]). Moreover, previous pharmacokinetic studies suggest that the flibanserin doses tested here would be associated with plasma levels spanning levels produced in humans by the recommended therapeutic dose of 100 mg PO [34, 43].…”

Section: Discussionmentioning

confidence: 92%

“…For example, flibanserin doses of 8–16 mg/kg (IP) or 45 mg/kg (PO), which produced similar plasma flibanserin levels, decreased measures of spontaneous locomotion in female and male rats [6, 44]. Moreover, this preclinical evidence for flibanserin effectiveness to decrease rates of operant responding and locomotor activity may be related to evidence for flibanserin-induced fatigue, somnolence and sedation in humans [8, 34].…”

Section: Discussionmentioning

confidence: 99%

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Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

Lazenka

Blough

Negus

2016

The Journal of Sexual Medicine

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INTRODUCTION Flibanserin is a serotonin receptor subtype 1A (5HT1A) agonist and 2A (5HT2A) antagonist that has been approved by the Food and Drug Administration for treating female sexual interest/arousal disorder. Little is known about the abuse potential of flibanserin. AIM This study examined abuse-related effects of flibanserin in rats using an intracranial self-stimulation (ICSS) procedure that has been used previously to evaluate abuse potential of other drugs. METHODS Adult female and male Sprague-Dawley rats with electrodes implanted in the medial forebrain bundle were trained to lever press for electrical brain stimulation under a “frequency-rate” ICSS procedure. In this procedure, increasing frequencies of brain stimulation maintain increasing rates of responding. Drugs of abuse typically increase (or “facilitate”) ICSS rates and produce leftward/upward shifts in ICSS frequency-rate curves, whereas drugs that lack abuse potential typically do not alter or only decrease ICSS rates. Initial studies determined the potency and time course of effects on ICSS produced by acute flibanserin (1.0, 3.2 and 10.0 mg/kg). Subsequent studies determined effects of flibanserin (3.2–18 mg/kg) before and after a regimen of repeated flibanserin administration (5.6 mg/kg/day x 5 days). Effects of the abused stimulant amphetamine (1.0 mg/kg) were examined as a positive control. MAIN OUTCOME MEASURE Flibanserin effects on ICSS frequency-rate curves in female and male rats were examined and compared to effects of amphetamine. RESULTS Baseline ICSS frequency-rate curves were similar in female and male rats. Both acute and repeated administration of flibanserin produced only decreases in ICSS rates, and rate-decreasing effects of the highest flibanserin dose (10 mg/kg) were greater in females than males. In contrast to flibanserin, amphetamine produced an abuse-related increase in ICSS rates that did not differ between females and males. CONCLUSIONS These results suggest that flibanserin has low abuse potential. Additionally, this study suggests that females may be more sensitive than males to rate-decreasing effects of high flibanserin doses.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

Lazenka

Blough

Negus

2016

The Journal of Sexual Medicine

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“…at stressful situations [11]. This may be reflected in the dose-dependent effect of 5-HT1A agonist on anxiety measured in unconditioned anxiety tests: low doses of were anxiolytic, while high doses were anxiogenic [1,7,19]. Low doses may result in different 5-HT release pattern and extracellular level and consequently different activation of 5-HT receptor subsets which is manifested in decreased anxiety [17,27].…”

Section: The Effect Of Buspironementioning

confidence: 99%

The anxiolytic buspirone shifts coping strategy in novel environmental context of mice with different anxious phenotype

Horváth¹,

Szögi²,

Müller³

et al. 2013

Behavioural Brain Research

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“…As each receptor does not have the same affinity to certain odorous substances, different concentrations of the same substance would activate various neuronal pathways differently [23]. Various endogenous factors such as hormones, cytokines, and neurotransmitters are supposed to be involved in the stress-induced hyperthermia [12,15,21,22], and actually the administration of certain drugs (e.g., adrenaline-beta antagonists, 5-HT1A or 2A receptor antagonists, NOS inhibitors or prostaglandin synthesis blockers) have been reported to suppress this stress-induced hyperthermia [2,10,14,18]. Why the concentration-effect of alphapinene was exerted differently among autonomic parameters has not bee determined, though one possible explanation appears to be based on this hypothesis regarding differing thresholds among neural pathways to a given odor.…”

mentioning

confidence: 99%

Effects of Alpha-Pinene Odor in Different Concentrations on Stress-Induced Hyperthermia in Rats

Akutsu

Kikusui

Takeuchi

et al. 2003

The Journal of Veterinary Medical Science

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ABSTRACT. Stress-induced hyperthermia is observed in animals exposed to stressful conditions. In our previous study, plant-derived fragrances such as green odor and alpha-pinene were shown to suppress this stress response in rats. In the present study, we examined the concentration-dependence of the alpha-pinene effects on stress-induced hyperthermia. Male rats carrying telemetry transmitters were transferred individually to a new cage containing bedding that had been sprayed with 0.3, 0.03, and 0.003% concentrations of alphapinene or control solvent. Following transfer to the novel environment, the body temperature increased significantly, and this response was clearly suppressed when the cage was scattered with 0.03% alpha-pinene only. These results suggest that the effect of alpha -pinene on stress-induced hyperthermia can be observed only at a certain concentration. KEY WORDS: alpha-pinene, concentration effect, hyperthermia.J. Vet. Med. Sci. 65(9): 1023-1025, 2003 When an animal is exposed to stressful situations, autonomic responses including a temporary increase of body temperature, namely stress-induced hyperthermia or emotional fever, have been observed in several species [3,4,[6][7][8][9][24][25][26]. Recent studies have suggested that in phylogeny this stress response involving body temperature has emerged between amphibians and reptiles [5]. In our previous study, it was revealed that an external olfactory stimulation could affect this autonomic stress response. Namely, plant-derived fragrances such as green odor and alphapinene showed ameliorative effects on stress-induced hyperthermia [1]. In addition, by using this model Kikusui et al. could also show an opposite effect in which exposure to alarm pheromones resulted in an aggravation of this hyperthermia [13]. When the odorant concentration was changed, the impression or the effects accompanying that odor to the physiological response and behavior in vivo could be different. For example, the event-related potential P300 was altered its amplitude by emotional change, and the experiment using components of the green odor induced different amplitudes of P300 depending on its concentration [20]. Feeding behavior of goats was suppressed by only higher concentration of trans-2-hexenal [11]. These results suggest that each odorant has a certain concentration at which it is most effective. In the present study we therefore examined concentration-dependence of the effect of alphapinene on stress-induced hyperthermia by preparing both lower (0.003%) and higher (0.3%) concentrations in addition to the concentration (0.03%) that in our previous study was confirmed to be effective.The basic experimental procedures and animals were as described previously [1]. Briefly, male Wistar rats (9 weeks old: Clea Japan, Inc., Tokyo, Japan) weighing approximately 230-300 g were housed in groups of 4 animals per cage with wood shavings (Soft chip: Japan SLC, Inc

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Behavioral Effects of Flibanserin (BIMT 17)

Cited by 18 publications

References 62 publications

Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

The anxiolytic buspirone shifts coping strategy in novel environmental context of mice with different anxious phenotype

Effects of Alpha-Pinene Odor in Different Concentrations on Stress-Induced Hyperthermia in Rats

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