Modulation of brain stem monoamines and gamma-aminobutyric acid by NK1 receptors in rats.
To understand the role of substance P in stress, anxiety and depression, we have investigated in rats the relationship between NK1 receptors and monoamines or GABA, and between substance P and serotonin (5-HT) in brain stem neurons by immunohistochemical double-staining techniques. In the periaqueductal gray and dorsal raphe nucleus, there was no colocalization between NK1 and 5-HT or between NK1 and tyrosine hydroxylase (a marker for adrenaline and dopamine neurons). However, many GABA-positive neurons (> 50%) were NK1 positive, and some substance P-positive neurons were 5-HT positive as well. Almost all locus coeruleus noradrenaline neurons were NK1 positive. Therefore, substance P may promote stress by activating noradrenaline neurons directly and inhibiting 5-HT neurons indirectly via GABA neurons.
Ma
Qing-Ping
QP
Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, UK. qingping_ma@merck.com
Bleasdale
Catherine
C
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D007150:Immunohistochemistry; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010487:Periaqueductal Gray / Q000166:cytology / Q000378:metabolism*; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015306:Biogenic Monoamines; D018040:Receptors, Neurokinin-1; D012701:Serotonin; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine