In vivo release of catecholamines in the locus coeruleus.
To investigate the release of endogenous dopamine, noradrenaline and adrenaline in the locus coeruleus, this brain area was superfused with artificial cerebrospinal fluid (CSF) through push-pull cannulae and the release of catecholamines was determined in the superfusate radioenzymatically. Collection of superfusates in time periods of 10 min revealed that release rates of the three catecholamines fluctuated, thus pointing to the existence of ultradian rhythms with following mean periods (minutes per cycle): noradrenaline 52 +/- 4, dopamine 37 +/- 2, adrenaline 36 +/- 2. The rhythm frequency of noradrenaline was significantly lower than the frequencies of dopamine and adrenaline. When the locus coeruleus was superfused with neuroactive drugs, superfusates were collected in time periods of 3 min. Superfusion with tetrodotoxin (1 mumol l-1) for 12 min elicited a prompt and sustained decrease (-70%) in the release rates of dopamine and adrenaline. The release rate of noradrenaline was also reduced, although to a lesser extent (-40%). Superfusion with veratridine (50 mumol l-1) led to an immediate and very pronounced enhancement in the release rates of dopamine, noradrenaline and adrenaline. The veratridine-induced increase in catecholamine outflow was decreased strongly by simultaneous superfusion with tetrodotoxin. The findings suggest that the release of endogenous catecholamines in the locus coeruleus fluctuates according to ultradian rhythms. Changes in the release on superfusion with veratridine and tetrodotoxin demonstrate the neuronal origin of the three catecholamines. The observed differences in the release characteristics between noradrenaline on the one hand and dopamine and adrenaline on the other might indicate that noradrenaline is partly released from somatodendritic sites of the noradrenergic cell bodies in the locus coeruleus.
Singewald
N
N
Institut für Pharmakologie und Toxikologie, Universität Innsbruck, Austria.
Schneider
C
C
Pfitscher
A
A
Philippu
A
A
D000818:Animals; D002404:Catheterization; D002415:Cats; D002555:Cerebrospinal Fluid; D004298:Dopamine / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism*; D005260:Female; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D013779:Tetrodotoxin; D014701:Veratridine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine