Effects of melatonin and agomelatine in anxiety-related procedures in rats: interaction with diazepam.
The anxiolytic potential of melatonin and agomelatine, a potent MT(1/2) receptor agonist, and their combined effects with diazepam, were investigated in rats using the punished drinking test, the safety signal withdrawal operant paradigm, the elevated-plus-maze and hypophagia-induced novelty. In the punished drinking test, evening injections of melatonin (80 mg/kg, IP, but not 20 and 40 mg/kg) and agomelatine (40 mg/kg, IP) increased the number of foot shocks received. However, neither melatonin (40-80 mg/kg) nor agomelatine (20-40 mg/kg) released response suppression during the period associated with the safety signal withdrawal and affected rats' behaviour in the elevated-plus-maze. Furthermore, agomelatine (40 mg/kg) did not enhance food consumption in unfamiliar environment. However, the co-administration of melatonin (80 mg/kg) or agomelatine (20-40 mg/kg) with diazepam, at a dose (0.25 mg/kg) inactive on its own, induced an anxiolytic-like effect in the punished drinking test and the elevated plus-maze. These results indicate that, although mostly devoid of anxiolytic-like action per se, melatonin and agomelatine can potentiate the anxiolytic effects of diazepam.
Loiseau
Florence
F
INSERM, U677, Paris, F-75013 France.
Le Bihan
Claudine
C
Hamon
Michel
M
Thiébot
Marie-Hélène
MH
D000081:Acetamides / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000378:metabolism / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009281:Naphthalenes
D000081:Acetamides; D003975:Diazepam; D008550:Melatonin; C084711:agomelatine; D009281:Naphthalenes