Antidepressant-like effects of agomelatine, melatonin and the NK1 receptor antagonist GR205171 in impulsive-related behaviour in rats.
BACKGROUND
Substance P receptor [neurokinin1 (NK1-R)] antagonists and melatonin(1/2) receptor (MT(1/2)-R) agonists have been claimed to be potential antidepressants (ADs). In animals, these compounds are active in validated models responsive to ADs, such as forced swimming test and chronic mild stress paradigms. Classical AD drugs are also known to be effective in pathologies characterized by an impulse control deficiency. In line with this clinical observation, previous studies demonstrated that classical ADs increased the capacity to wait for food reward in rats subjected to a paradigm aimed at assessing impulsive-related behaviour.


OBJECTIVE
This study was conducted to investigate the effects of two MT(1/2)-R agonists, melatonin and agomelatine, and a NK1-R antagonist, GR205171, on tolerance to delay of food reward in rats.


METHODS
Fasting rats were trained in a T-maze and allowed to choose between two magnitudes of reward: immediate but small reward (two pellets) vs 25-s delayed but large reward (ten pellets). Under this alternative, vehicle-injected rats selected the large-but-delayed reinforcer in less than 40% of the trials.


RESULTS
Like the established ADs clomipramine (8 mg kg(-1), i.p.) and fluvoxamine (4 mg kg(-1), i.p.), melatonin (3 and 10 mg kg(-1), i.p.), agomelatine (10 and 30 mg kg(-1), i.p.) and GR205171 (30 mg kg(-1) but not 10 mg kg(-1), s.c.) significantly increased the number of choices of the large-but-delayed reward. The effect of melatonin (3 mg kg(-1), i.p.) was not counteracted by the MT(1/2)-R antagonist S22153 (40 mg kg(-1), i.p.) that exerted no effect on its own.


CONCLUSIONS
These results suggest that MT(1/2)-R agonists and NK1-R antagonists enhance rats' tolerance to delay of gratification, an effect which may reflect their ability to improve impulse control. Further investigations are necessary to clarify the neurobiological mechanisms responsible for this effect.
INSERM U.677 (ex U.288), Faculty of Medicine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris, Cedex 13, France.
Florence
F
Loiseau
Claudine
C
Le Bihan
Michel
M
Hamon
Marie-Hélène
MH
Thiébot
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001070:Appetitive Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D007175:Impulsive Behavior / Q000523:psychology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009042:Motivation; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044122:Receptor, Melatonin, MT1 / Q000819:agonists*; D044123:Receptor, Melatonin, MT2 / Q000819:agonists*; D012055:Reinforcement Schedule; D013777:Tetrazoles / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology; D009281:Naphthalenes
D000081:Acetamides; D000928:Antidepressive Agents; D008550:Melatonin; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D013777:Tetrazoles; D013876:Thiophenes; C120267:S 22153; C084711:agomelatine; D009281:Naphthalenes; C103207:vofopitant