Late embryonic ritanserin exposure fails to alter normal responses to immune system stimulation in young chicks.
Prior studies in our laboratory have demonstrated that prenatal treatment with the serotonin2 (5-HT2) antagonist ritanserin is effective in blocking some of the lethal, dysmorphic, cardiovascular, and behavioral consequences of excessive direct or indirect stimulation of 5-HT2 receptors in the developing chicken. The efficacious dose range for ritanserin in these studies had very little or no effect on the above measures of toxicity when administered alone. In the present study, we extend our characterization of ritanserin's potential toxicity, or lack thereof, to include the normal behavioral and endocrine responses to immune system stimulation by the endotoxin lipopolysaccharide (LPS). LPS administration induces a syndrome collectively known as sickness behavior, manifest as altered thermoregulatory processes leading to fever, and increased serum concentrations of neuroendocrine hormones, including corticosterone. These survival-promoting responses to LPS were assessed in young chickens that had been treated with doses of ritanserin ranging from 0 to 2.7 mg/kg on embryonic day 17 (E17). When sickness behavior was assessed in 5-7-day-old chicks 1 h post-LPS injection, E17 ritanserin-treated subjects did not differ from controls. At 4-6 h post-LPS, 4-day-old chicks displayed a robust fever, and E17 ritanserin did not affect the magnitude of this response. Similarly, E17 ritanserin treatment failed to affect corticosterone concentrations 2 h post-LPS in 14-day-old chicks. Thus, ritanserin treatment during late embryogenesis, a time when it is effective against direct and indirect acting 5-HT2 agonists, failed to modify the survival promoting and beneficial interactions between the nervous, endocrine, and immune systems that are elicited following immunostimulation.
Schrott
L M
LM
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
Sweeney
W A
WA
Bodensteiner
K E
KE
Sparber
S B
SB
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D002642:Chick Embryo; D002645:Chickens / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D007107:Immune System / Q000187:drug effects* / Q000196:embryology*; D008070:Lipopolysaccharides / Q000633:toxicity; D016713:Ritanserin / Q000633:toxicity*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D014150:Antipsychotic Agents; D008070:Lipopolysaccharides; D012702:Serotonin Antagonists; D016713:Ritanserin; D003345:Corticosterone