Changes in right atrial catecholamine content in naïve rats and after naloxone-induced withdrawal.
In this study, we determined if changes in heart catecholamine content during naloxone-induced withdrawal correlated with modifications in heart rate. In addition, we determined plasma concentrations of corticosterone as an index of the hypothalamo-pituitary-adrenal (HPA) axis. The effects of naloxone on norepinephrine, epinephrine or dopamine content and turnover, plasma concentrations of corticosterone and the mechanical response of the right atria of the rat were studied. Male rats were implanted with placebo or morphine pellets for 7 days. On the day of sacrifice, animals were injected with saline or naloxone 1 mg kg-1 s.c. to precipitate a withdrawal syndrome. Administration of naloxone to morphine-treated (tolerant) animals induced a decrease in atrial content of norepinephrine, epinephrine and dopamine (290.2 (11.9) ng g-1, 15.6 (2.1) ng g-1 and 9.52 (0.5) ng g-1, respectively) and an increase (1.38 (0.2) ng g-1 in the dihydroxy phenyl acetic acid/dopamine (DOPAC/DA) ratio. Administration of naloxone to morphine-treated animals enhanced plasma concentrations of corticosterone (435.8 (27.6) ng ml-1). In the isolated right atria, L-naloxone induced an increase in atrial rate in preparations from morphine-treated rats whereas in placebo-pelleted (naïve) rats, L-naloxone induced a decrease. In contrast, administration of D-naloxone (inactive isomer) produced a decrease in atrial rate in preparations from placebo or morphine-treated rats. We conclude that this study has provided evidence that naloxone-induced withdrawal was characterized by activation of catecholaminergic neurones in the heart that was accompanied by an increase in atrial rate.
Rabadán
J V
JV
Department of Physiology and Pharmacology, University School of Medicine, Murcia, Spain.
Milanés
M V
MV
Laorden
M L
ML
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009270:Naloxone / Q000009:adverse effects*; D009292:Narcotic Antagonists / Q000009:adverse effects*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D002395:Catecholamines; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; D003345:Corticosterone