Anxiolytic-like action of the antidepressant agomelatine (S 20098) after a social defeat requires the integrity of the SCN.
In rats, social defeat by an aggressive opponent induces a state of anxiety, shown by a decrease in time spent on active explorative behaviour, an increase in immobility, a clear decrease in frequency of all active behavioural parameters (enhanced passivity). We tested the hypothesis whether acute or sub-chronic agomelatine would antagonize the negative consequences of a social defeat. As many chronobiological actions of melatonin and its receptor agonist agomelatine require the integrity of the suprachiasmatic nuclei (SCN), we examined whether the anxiolytic-like action of agomelatine 1 day after a social defeat is still present in SCN-lesioned rats. Sub-chronic administration of agomelatine caused a clear reduction of the social defeat induced behavioural consequences. A single agomelatine injection prior to the post-defeat test was less effective and a single melatonin injection was hardly effective. SCN lesion did not affect the anxiety reaction after a social defeat. Thus, sub-chronic agomelatine treatment or a single agomelatine injection reduced a state of anxiety and passivity caused by asocial defeat. The defeat-induced behavioural changes do not depend on the SCN but agomelatine showed its anxiolytic action only in sham-lesioned animals, which indicates that the anxiolytic-like action of agomelatine requires the integrity of the SCN. Mechanisms sustaining this activity are discussed.
Tuma
Jolanda
J
Department of Animal Physiology, University of Groningen, Kerklaan, 30, 9751 NN, Haren, The Netherlands.
Strubbe
Jan H
JH
Mocaër
Elisabeth
E
Koolhaas
Jaap M
JM
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012919:Social Behavior; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes
D000081:Acetamides; D000928:Antidepressive Agents; D006993:Hypnotics and Sedatives; C084711:agomelatine; D009281:Naphthalenes