The antidepressant agomelatine inhibits stress-mediated changes in amino acid efflux in the rat hippocampus and amygdala.
Agomelatine is a potent melatonergic (MT1 and MT2) receptor agonist and 5HT(2C) antagonist that is an effective antidepressant in animal models of depression and in patients suffering from depression. Our recent studies revealed that acute restraint stress increases extracellular levels of glutamate and GABA and that these increases in amino acid efflux are inhibited by some but not all antidepressants. In view of the increasing evidence supporting a role of amino acids in the pathology of depression, the current study examined whether acute stress-mediated changes in glutamate and GABA neurotransmission are modulated by agomelatine. In agreement with our previous work, acute stress increases extracellular glutamate levels in the basolateral nucleus of the amygdala (BLA). Similarly, acute stress increases glutamate efflux in the central nucleus of the amygdala (CeA). In the hippocampus, acute stress increases glutamate efflux and elicits an oscillatory pattern of GABA efflux. Agomelatine administration (40mg/kg ip) prior to acute stress inhibited stress-mediated increases in glutamate efflux in the hippocampus, BLA and CeA. These results demonstrate that acute agomelatine administration effectively inhibits acute stress-mediated changes in extracellular glutamate in the rat hippocampus and amygdala. While acute stress did not modulate GABA efflux in these regions, agomelatine treatment induced an overall reduction of GABA levels in the hippocampus. These data suggest that agomelatine modulates amino acid efflux in limbic structures implicated in major depressive disorder.
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Rd, Columbia, SC 29208, USA.
Lawrence P
LP
Reagan
Leah R
LR
Reznikov
Ashlie N
AN
Evans
Cecilia
C
Gabriel
Elisabeth
E
Mocaër
Jim R
JR
Fadel
D000081:Acetamides / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D009281:Naphthalenes
D000081:Acetamides; D000928:Antidepressive Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C084711:agomelatine; D009281:Naphthalenes