title: Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats.
abstract: BACKGROUND
  Flibanserin is a serotonin receptor subtype 1A agonist and 2A antagonist that has been approved by the Food and Drug Administration for treating female sexual interest and arousal disorder. Little is known about the abuse potential of flibanserin.
  
  
  OBJECTIVE
  To examine abuse-related effects of flibanserin in rats using an intracranial self-stimulation (ICSS) procedure previously used to evaluate the abuse potential of other drugs.
  
  
  METHODS
  Adult female and male Sprague-Dawley rats with electrodes implanted in the medial forebrain bundle were trained to press a lever 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 and 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 administration (1.0, 3.2 and 10.0 mg/kg). Subsequent studies determined the effects of flibanserin (3.2-18 mg/kg) before and after a regimen of repeated flibanserin administration (5.6 mg/kg/d for 5 days). Effects of the abused stimulant amphetamine (1.0 mg/kg) were examined as a positive control.
  
  
  METHODS
  Flibanserin effects on ICSS frequency-rate curves in female and male rats were examined and compared with the effects of amphetamine.
  
  
  RESULTS
  Baseline ICSS frequency-rate curves were similar in female and male rats. Acute and repeated administrations of flibanserin produced only decreases in ICSS rates, and rate-decreasing effects of the highest flibanserin dose (10 mg/kg) were greater in female than in male rats. In contrast to flibanserin, amphetamine produced an abuse-related increase in ICSS rates that did not differ between female and male rats.
  
  
  CONCLUSIONS
  These results suggest that flibanserin has low abuse potential. In addition, this study suggests that female rats might be more sensitive than male rats to the rate-decreasing effects of high flibanserin doses.
authors.affiliation: Department of Pharmacology and Toxicology and Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: lazenkamf@vcu.edu.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Lazenka
authors.affiliation: Center for Drug Discovery, Research Triangle Institute, Research Triangle Park, NC, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Blough
authors.affiliation: Department of Pharmacology and Toxicology and Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D003216:Conditioning, Operant / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation / Q000187:drug effects*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000473:pathology*; D014481:United States
chemical_list: D001562:Benzimidazoles; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C098107:flibanserin
keywords: Drug Abuse; Female; Intracranial Self-Stimulation; Rat; Serotonin Receptor; Sex Differences
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