Effect of repeated administration of paroxetine and electroconvulsive shock on the proliferative response of lymphocytes and the synthesis of nitric oxide by macrophages in rats.
OBJECTIVE
We sought to determine whether chronic administration of paroxetine and electroconvulsive shock (ECS), given separately or jointly, changes the proliferative response of T and B lymphocytes stimulated by mitogens and affect the production of nitric oxide (NO) by peritoneal macrophages.


METHODS
The experiment was conducted on male Wistar rats receiving treatment once daily for 12 consecutive days. Control animals were injected intraperitoneally (ip) with sterile distilled water (2 mL/kg) and were subjected to sham ECS. Paroxetine was administered ip in a dose of 10 mg/kg of body weight. ECS (150 mA, 50 Hz, 0.5 seconds) was delivered through ear clips. For combined treatment, paroxetine was given 30 minutes before ECS. The rats were killed 24 hours after the last treatment. Then, the proliferative response of splenocytes was induced by concanavalin A (Con A), lipopolysaccharide (LPS), or pokeweed mitogen and those of thymocytes by Con A and was later assessed by a standard [H]-thymidine incorporation assay. The spontaneous or induced (with LPS) NO synthesis in peritoneal macrophages was assessed as nitrite accumulation in 24-hour culture supernatants using the Griess reaction.


RESULTS
Only chronic treatment with ECS alone significantly increased the proliferative response of splenocytes to stimulation with Con A or LPS. The response of thymocytes was not changed in any group tested. Both the spontaneous NO synthesis and that induced with LPS in macrophages were significantly decreased only in rats receiving ECS.


CONCLUSIONS
We suggest that the ECS-induced suppression of NO synthesis by macrophages, resulting from the noradrenergic component of ECS action, may be responsible for the enhanced proliferative response of lymphocytes. Our data are in line with the results of other authors indicating that paroxetine and/or ECS modulate the immune system indirectly via the neuroendocrine system. The relatively high efficacy of ECS in the therapy for depression may be attributable to the ECS-evoked long-lasting changes in the immune system, which supports the macrophage theory of depression.
Roman
Adam
A
Laboratory of Intracellular Signaling, Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. roman@if-pan.krakow.pl
Nalepa
Irena
I
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004334:Drug Administration Schedule; D004597:Electroshock; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009929:Organ Size / Q000187:drug effects; D017374:Paroxetine / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology
D018687:Antidepressive Agents, Second-Generation; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D017374:Paroxetine