Nitroglycerin-induced activation of monoaminergic transmission in the rat.
When administered to migraine patients, nitroglycerin induces a spontaneous-like migraine attack, with a latency of several hours. Nitroglycerin acts directly and/or indirectly on the central nervous system, through the release of nitric oxide (NO). Systemic administration of the drug to the rat causes neuronal activation in selected subcortical areas, particularly in monoaminergic nuclei of the brainstem. In this study, we sought to investigate whether this activation correlates with changes in monoaminergic neurotransmission. For this purpose, we evaluated the tissue levels of catecholamines and serotonin in the hypothalamus, mesencephalon, pons and medulla of rats treated with systemic nitroglycerin or vehicle, at different time points (1, 2 and 4 h). We also evaluated the peripheral sympathetic response to the drug by measuring the concentrations of plasma catecholamines. Nitroglycerin caused an early (1 h) increase in cerebral (pons) and plasma levels of norepinephrine, followed by a delayed (4 h) decrease in medullary and pontine levels of serotonin. The initial noradrenergic activation may reflect the autonomic response to the rapid cardiovascular effects of the drug, while the delayed response may result from the interaction of nitroglycerin-released NO and 5-HT in central areas devoted to the modulation of nociception. These data might therefore help to clarify the mechanisms underlying the delayed migraine attack observed in migraine sufferers after systemic administration of nitroglycerin.
Tassorelli
C
C
IRCCS Neurological Institute, C. Mondino Foundation, Pavia, Italy. cristina.tassorelli@mondino.it
Blandini
F
F
Costa
A
A
Preza
E
E
Nappi
G
G
D000818:Animals; D015306:Biogenic Monoamines / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000097:blood / Q000378:metabolism; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D015306:Biogenic Monoamines; D012701:Serotonin; D005996:Nitroglycerin; D004298:Dopamine; D009638:Norepinephrine