Effects of U-50,488H withdrawal on catecholaminergic neurones of the rat ventricle.
1. In the present study the changes in noradrenaline (NA) and dopamine (DA) content and turnover during naloxone-induced withdrawal were analysed in the right ventricle of rats chronically treated with the kappa-agonist U-50,488H. 2. Rats were rendered tolerant by administration of U-50,488H twice a day for 4 days. On the day of death the animals were injected with saline or naloxone (3 mg kg(-1), s.c.) to precipitate a withdrawal syndrome. 3. After naloxone administration to U-50,488H- treated rats we found neither behaviour signs of physical dependence nor changes in the tissue content of noradrenaline (NA). However, naloxone induced a decrease in both cardiac normetanephrine (NM) levels and NA turnover. 4. Similarly, naloxone enhanced the dopamine content and decreased the 3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover. 5. Importantly and in contrast to mu-agonists, the present results demonstrate that U-50,488H withdrawal produced a decrease in the NA and dopamine turnover, without behavioural signs of physical dependence.
Department of Physiology and Pharmacology, University School of Medicine, Murcia, Spain.
M V
MV
Milanés
M L
ML
Laorden
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009647:Normetanephrine; D015102:3,4-Dihydroxyphenylacetic Acid; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004298:Dopamine; D009638:Norepinephrine