Physical Dependence in the Rat Induced by Slow Release Morphine: Dose-Response, Time Course and Brain Biogenic Amines

Abstract

1. Physical dependence was induced in rats by administration of a slow release morphine emulsion (morphine SR), and assessed by scoring abstinence signs and temperature changes after i.p. administration of naloxone (5 mg/kg). Three groups of rats received doses of 75, 100 or 150 mg/kg of morphine SR. Dependence was evaluated in each of these groups after 24, 48 and 72 h. 2. The effect of these treatments at the different times on brain levels of serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine was determined. 3. A ceiling level of dependence was reached 24 h after 75 and 100 mg/kg and 48 h after 150 mg/kg of morphine SR. 4. These different treatments produced no significant effect on the brain levels of noradrenaline, dopamine or serotonin. The levels of 5-hydroxyindoleacetic acid were significantly raised in morphine-dependent rats and the changes correlated well with the changes in abstinence behaviour and temperature after naloxone. 5. The results suggest that a relationship exists between serotonin turnover and physical dependence on morphine.

Dissociation of Increased 5‐hydroxyindoleacetic Acid Levels and Physical Dependence: The Effects of Naloxone

“…Naloxone SR had little effect on the levels of noradrenaline, dopamine, homovanillic acid and serotonin; however, at all three doses used (75, 100 and 150mg/kg) and at the three times after administration (24, 48 and 72 h), naloxone SR elevated the brain levels of 5-hydroxyindoleacetic acid. This finding is similar to the results obtained with morphine SR (Laska & Fennessy, 1976). The increases in 5-hydroxyindoleacetic acid after naloxone SR appear to occur in a dose-related manner which was not the case after morphine SR.…”

“…In the groups of rats treated with naloxone SR for 72h, body weight was measured daily and also for 55h after the injection of naltrexone. The development of physical dependence, using the same strain and sex of rats and under the same conditions, has been reported for morphine SR in doses of 75,100 and 150 mg/kg (Laska & Fennessy, 1976).…”

“…In our present study, doses of 75, 100 and 150 mg/kgnaloxone were administered in the form of a slow release emulsion. These doses were chosen primarily to enable comparison of the effects produced by naloxone SR with those produced by similar doses of morphine SR as previously reported by Laska & Fennessy (1976). Naltrexone has been reported to be an orally active, relatively 'pure' narcotic antagonist which is approximately twice as potent as naloxone in antagonizing morphine analgesia, and is longer acting (Blumberg & Dayton, 1972).…”

“…After 24,48 or 72 h the animals were decapitated, the brains rapidly removed and blotted free of excess blood and frozen in liquid nitrogen. The monoamines noradrenaline, dopamine and serotonin, and also 5-hydroxyindoleacetic acid, were extracted and assayed as previously described (Laska & Fennessy, 1976). In addition, the amount of the acid metabolite of dopamine, homovanillic acid, was determined in the extract by the fluorometric method of Anden, Roos & Werdinius (1963).…”

Central Aminergic Mechanisms Associated With the Clonidine Withdrawal Syndrome

“…Two hours after the last injection, similarly treated groups of rats were decapitated for subsequent spectrophotofluorimetric determination of regional brain concentrations of noradrenaline, dopamine, homovanillic acid, serotonin, 5-hydroxyindoleacetic acid and histamine as described previously (Laska & Fennessy, 1976;Lewis, Fennessy, Laska & Taylor, 1980).…”