Mechanism of action of flibanserin in the learned helplessness paradigm in rats

Borsini, Franco; Cesana, Raffaele

doi:10.1016/s0014-2999(01)01495-9

Cited by 21 publications

(23 citation statements)

References 66 publications

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“…These results agree with previous reports which demonstrated that depletion of 5-HT using PCPA does not alter baseline behavior in many antidepressant tests, such as the mouse TST and FST, the modified rat FST, or the learned helplessness paradigm (Borsini and Cesana 2001;Gavioli et al 2004;Mayorga et al 2001;Page et al 1999;Wieland and Lucki 1990). Similarly, destruction of serotonergic neurons with 5,7-DHT did not alter baseline behavior in the rat FST or in the learned helplessness paradigm (Cervo and Samanin 1987;Cervo et al 1991;Lucki et al 1994;Soubrie et al 1986).…”

Section: Discussionsupporting

confidence: 92%

Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test

et al. 2007

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Section: Discussionsupporting

confidence: 92%

Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test

et al. 2007

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“…Likewise, Lieben et al 2006 reported that chronic reduction of central 5-HT concentrations by 5,7-DHT lesion of the DRN did not affect the immobility in the FST. In addition, it has been reported that the depletion of 5-HT using PCPA does not alter baseline behavior in many tests such as the tail suspension test (O'Leary et al 2007) and FST (Wieland and Lucki 1990), the modified rat FST (Page et al 1999), or learned helplessness paradigm (Borsini and Cesena 2001). The findings of the present study are also consistent with those of several clinical studies examining the effect of 5-HT depletion.…”

Section: Discussionsupporting

confidence: 90%

Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on the antidepressant-like action of tramadol in the unpredictable chronic mild stress in mice

et al. 2008

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“…In the only preclinical study published to date, flibanserin did not produce a conditioned place preference in male rats [13], but place conditioning studies have not been conducted in females (the sex for which the drug is approved for treatment of sexual interest/arousal disorder), and flibanserin has not been studied in either sex in drug self-administration or ICSS procedures. However, drugs with related pharmacological mechanisms of action as either 5HT1A agonists or 5HT2A antagonists have been tested in both place conditioning and ICSS procedures, and these studies suggest that 5HT1A agonist effects in particular may contribute to abuse potential.…”

Section: Introductionmentioning

confidence: 99%

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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Mechanism of action of flibanserin in the learned helplessness paradigm in rats

Cited by 21 publications

References 66 publications

Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test

Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test

Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on the antidepressant-like action of tramadol in the unpredictable chronic mild stress in mice

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

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