Altered expression of autonomic neurotransmitter receptors and proliferative responses in lymphocytes from a chronic mild stress model of depression: effects of fluoxetine.
We studied beta-adrenergic and muscarinic cholinergic receptor (MR) expression and proliferative response in lymphocytes from animals under chronic mild stress (CMS) model of depression (CMS animals). Animals were subjected to CMS (periods of food or water deprivation, changes in lighting conditions, tilted cage, etc.) for 12 weeks. CMS lymphocytes showed an altered mitogen-induced proliferation. CMS-B and -T lymphocytes showed an increment on beta-adrenoceptor number and on intracellular responses to a beta-agonist. CMS-T cells showed higher MR expression and lower cGMP responses than normal lymphocytes. MR were not detectable in normal B cells while CMS-B cells showed both MR expression and cGMP response. Beta and muscarinic stimulation influenced lymphocyte proliferative responses, in accordance with cAMP and cGMP responses. After 12 weeks of the CMS procedure, animals were treated with fluoxetine while the CMS procedure continued. Fluoxetine treatment reverted the alterations induced by CMS. These findings suggest a possible mechanism for the immune alterations found in depressive disorders and for the effect of fluoxetine treatment on immune response.
Edgar
Valeria Ayelli
VA
CEFYBO-CONICET, Serrano 669, Buenos Aires, 1414, Argentina.
Cremaschi
Graciela A
GA
Sterin-Borda
Leonor
L
Genaro
Ana María
AM
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016516:CD4-CD8 Ratio; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000096:biosynthesis*; D011976:Receptors, Muscarinic / Q000032:analysis / Q000096:biosynthesis*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D018687:Antidepressive Agents, Second-Generation; D007457:Iodine Radioisotopes; D008934:Mitogens; D018727:Muscarinic Antagonists; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D005473:Fluoxetine; D014316:Tritium; C047975:cyanopindolol; D011813:Quinuclidinyl Benzilate; D010869:Pindolol; D000242:Cyclic AMP; D006152:Cyclic GMP