Further characterization of the long-term effect of RU24722 on tyrosine hydroxylase in the rat locus coeruleus.
Recent data have indicated that the long-lasting increase in tyrosine hydroxylase (TH) protein could be differently expressed in the anterior and posterior locus coeruleus (LC) after a single intraperitoneal injection of RU24722, which has been proposed as a potent activator of catecholaminergic systems. In the present study, we have evaluated the dose and time course responses and the effect of a repeated treatment with RU24722 at 3-day intervals on TH protein level in the anterior and posterior rat LC. The results showed that RU24722 induces a long-lasting increase of TH protein level in the anterior and posterior LC that was maximal 3 days following a single injection of 30 mg/kg. The increase in TH protein was maintained at a constant level after repeated administrations of RU24722 at 3-day intervals. Furthermore, we have investigated whether the effect of the drug on TH protein could be modulated via several hormonal systems. The long-term increase of TH steady-state content after RU24722 was still observed 15 days after castration, adrenalectomy, hypophysectomy, and thyroidectomy. The initial steady-state TH protein level was significantly higher in the anterior LC of thyroid- or hypophysectomized and in the posterior LC of hypophysectomized rats. However, this increase was reversed when animals were housed at 28 degrees C.
Schmitt
P
P
Laboratoire de Neuropharmacologie Moléculaire, UMR 105-CNRS, Lyon, France.
Reny-Palasse
V
V
Bourde
O
O
Garcia
C
C
Pujol
J F
JF
D000311:Adrenal Glands / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D007016:Hypophysectomy; D008125:Locus Coeruleus / Q000201:enzymology*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism; D013965:Thyroidectomy; D013997:Time Factors; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D014749:Vincamine / Q000031:analogs & derivatives* / Q000494:pharmacology
D014749:Vincamine; C044616:vindeburnol; D014446:Tyrosine 3-Monooxygenase