S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat.
S-adenosyl-L-methionine (SAM) has shown efficacy in speeding the onset of the antidepressant effect of imipramine in depressed patients. This effect may be related to their interactions at the serotonin(1A) (5-HT(1A)) receptors. Acute imipramine up-regulated the frontal cortex 5-HT(1A) receptors (B(max), 51.5 +/- 8.4 fmol/mg protein) vs. saline (B(max), 27.5 +/- 5.9 fmol/mg protein), and did not show antidepressant effect. Acute SAM and imipramine+SAM did not modify frontal cortex 5-HT(1A) receptors, and showed antidepressant effects (decrease of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the chronic treatments showed antidepressant effects and up-regulated the hippocampus 5-HT(1A) receptors. SAM prevents the 5-HT(1A) receptor up-regulation induced by acute imipramine in the frontal cortex. This mechanism may contribute to imipramine's antidepressant effect.
Bellido
Inmaculada
I
Department of Pharmacology and Clinical Therapeutics, School of Medicine, University of Malaga, Malaga, Spain. ibellido@uma.es
Gomez-Luque
Aurelio
A
Plaza
Antonio
A
Rius
Francisca
F
Ortiz
Pablo
P
Sanchez de la Cuesta
Felipe
F
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000819:agonists*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004347:Drug Interactions / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007099:Imipramine / Q000819:agonists*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D012436:S-Adenosylmethionine; D007099:Imipramine