Anxiolytic-like effects of escitalopram, citalopram, and R-citalopram in maternally separated mouse pups.
The S-enantiomer of citalopram, escitalopram, is a selective serotonin reuptake inhibitor (SSRI) that appears to be responsible for citalopram's antidepressant and anxiolytic effects. Clinically, escitalopram is reported to have fewer adverse side effects than do other SSRIs. This study compared escitalopram to other antidepressants in a preclinical procedure predicting anxiolytic-like effects of drugs. Carworth Farms Webster (CFW) mouse pups (7 days old) were separated from the dam and maintained at a temperature of 34 degrees C. Forty-five minutes after administering citalopram (0.56-10 mg/kg), escitalopram (0.0056-3 mg/kg), R-citalopram (1-10 mg/kg), paroxetine (0.3-3 mg/kg), fluoxetine (1-30 mg/kg), or venlafaxine (3-56 mg/kg) subcutaneously, the pups were placed individually on a 19.5 degrees C surface for 4 min. Ultrasonic vocalizations (USVs) (30-80 kHz), grid crossing, rolling (i.e., the pup turned on one side or its back), and colonic temperature were recorded. All the drugs reduced USV emission; escitalopram was the most potent (ED(50) 0.05 mg/kg), followed by paroxetine (0.17 mg/kg), citalopram (1.2 mg/kg), fluoxetine (4.3 mg/kg), R-citalopram (6 mg/kg), and venlafaxine (7 mg/kg). The doses that decreased USVs differed from those that increased motor activity. Increased grid crossing occurred after low doses of paroxetine (0.03 or 0.1 mg/kg) and fluoxetine (1 mg/kg), but only after the highest doses of the citalopram enantiomers and venlafaxine (0.3, 10, and 56 mg/kg, respectively). Except for escitalopram and venlafaxine, high doses of the treatments increased rolling. R-Citalopram caused a 10-fold rightward shift in escitalopram's dose-effect curve, suggesting that R-citalopram inhibits escitalopram's anxiolytic-like effects. These data support clinical findings that escitalopram is a potent, well tolerated SSRI with anxiolytic-like effects.
Department of Psychology, Tufts University, Medford, Massachusetts 02155, USA.
Eric W
EW
Fish
Sara
S
Faccidomo
Sandeep
S
Gupta
Klaus A
KA
Miczek
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001010:Anxiety, Separation / Q000188:drug therapy*; D001831:Body Temperature / Q000187:drug effects; D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D008426:Maternal Deprivation; D051379:Mice; D011597:Psychomotor Performance / Q000187:drug effects*; D011738:Pyrilamine / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
D014151:Anti-Anxiety Agents; D015283:Citalopram; D006634:Histamine H1 Antagonists; D011738:Pyrilamine; D017367:Selective Serotonin Reuptake Inhibitors