Antidepressant effects of citalopram and CRF receptor antagonist CP-154,526 in a rat model of depression.
Due to the interest in the antidepressant potential of nonpeptide corticotropin-releasing factor (CRF)(1) receptor antagonists, the present investigation examined the antidepressant-like effects of the CRF(1) receptor antagonist CP-154,526 on the exaggerated swim test immobility in the Flinders Sensitive Line (FSL) rat, a genetic animal model of depression. Chronic treatment with CP-154,526 (10 mg/kg; 2x day) for 14 days increased swimming in the Flinders Sensitive Line rats. Citalopram (5 and 10 mg/kg; 2x day) and desipramine (5 mg/kg; 1x day) also significantly increased swimming in the Flinders Sensitive Line rats, as expected. However, neither CP-154,526 nor citalopram (10 mg/kg) altered swimming times in the control Flinders Resistant Line (FRL) rats. Citalopram (10 mg/kg) and CP-154,526 also increased the abnormally low level of social interaction behavior in the Flinders Sensitive Line rats. These findings indicate that citalopram and CP154,526, a CRF(1) receptor antagonist, have both antidepressant and anxiolytic effects that can be detected in an experimental model of depression only and not in "normal" control animals.
Overstreet
David H
DH
Center for Alcohol Studies, CB #7178, 3009 Thurston-Bowles Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178, USA. dhover@med.unc.edu
Keeney
Adam
A
Hogg
Sandra
S
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012919:Social Behavior; D013550:Swimming
D000928:Antidepressive Agents; C101628:CP 154526; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D015283:Citalopram