Antidepressant properties of rotigotine in experimental models of depression.
Limited clinical data are available on the use of dopamine agonists for the control of motor function and also for the treatment of depression. This study was performed to evaluate the potential effects of the dopamine receptor agonist rotigotine in rat models of anxiety and depression. After repeated administration at doses of 0.05, 0.5, 1, and 5 mg/kg, rotigotine increased spontaneous motor activity at the 5 mg/kg dose after 3-5 days of treatment. At lower doses, the drug had no effect on locomotor activity. After a single administration, rotigotine had no anxiolytic activity in rats during the elevated plus-maze test or the Geller-Seifter conflict test. In the behavioral despair test (also known as the forced swim test), the 5 mg/kg dose of rotigotine enhanced the mobility of rats. Rotigotine (0.5, 1, and 5 mg/kg/day for 5 days) reversed the active avoidance deficit of helpless rats in the learned helplessness test, as shown by a significant decrease in escape failures after 3 to 4 days (0.5 mg/kg/day), 5 days (1 mg/kg/day), and 3 to 5 days (5 mg/kg/day) of treatment. During open-field testing of rats subjected to olfactory bulbectomy and given a 14-day schedule of rotigotine (0.3 mg/kg every 2 days), hyperactivity reversed according to a U-shaped dose-response curve. These results suggest that rotigotine may have antidepressant properties at doses of 1 mg/kg and lower. Potential effects at doses of 5 mg/kg and higher may be masked by an effect of the compound whereby general locomotor activity is enhanced.
Bertaina-Anglade
Valerie
V
Biotrial, Rennes, France.
La Rochelle
Christophe Drieu
CD
Scheller
Dieter K A
DK
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D006380:Helplessness, Learned; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D000928:Antidepressive Agents; D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine