Acute morphine effects on respiratory activity in mice with target deletion of the tachykinin 1 gene (Tac1-/-).
Search for physiological mechanisms which could antagonize the opioid-induced respiratory depression is of important clinical value. In this study, we investigated the acute effects of morphine on respiratory activity in genetically modified newborn (P2) mice with target deletion of the (Tac1 -/-) gene lacking substance P (SP) and neurokinin A (NKA). In vivo, as shown with whole-body flow barometric plethysmography technique, morphine induced significantly attenuated minute ventilation during intermittent hypoxia in control animals. In contrast, knockout mice revealed significant increase in minute ventilation. In vitro, in brainstem preparation, knockout mice demonstrated greater changes in burst frequency during intermittent anoxia challenge. The data suggest that hereditary deficiency in tachykinins, SP and NKA results in more robust hypoxic response in newborn Tac1-/- mice during respiratory depression induced by morphine.
Shvarev
Yuri
Y
Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden. Yuri.Shvarev@ki.se
Berner
Jonas
J
Bilkei-Gorzo
Andras
A
Lagercrantz
Hugo
H
Wickström
Ronny
R
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017353:Gene Deletion; D000860:Hypoxia / Q000235:genetics / Q000503:physiopathology; D066298:In Vitro Techniques; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D015288:Neurokinin A / Q000172:deficiency / Q000235:genetics; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D013373:Substance P / Q000172:deficiency / Q000235:genetics; D015320:Tachykinins / Q000172:deficiency* / Q000235:genetics*
D015320:Tachykinins; D013373:Substance P; D009020:Morphine; D015288:Neurokinin A