The effects of acute morphine treatment on the incorporation of [3H]L-lysine by normal and regenerating facial nucleus neurons.

Although opiates significantly alter RNA and protein synthesis in a variety of neuronal cell types, their effect on the biosynthetic activity of regenerating neurons has not been investigated. In the present study, the effect of morphine on the incorporation of [3H]L-lysine into proteins of facial nucleus neurons was examined by light microscopic radioautography. Silver grains present within various compartments of normal and regenerating (3-, 7-, 14- and 21 days post-axotomy) neurons from saline-treated Wistar rats were compared with the amount present in similar cells from animals receiving 40 mg/kg morphine sulfate i.v. At 14- and 21-days post-axotomy, regenerating neurons were larger and the grain count in the emulsion over these cells was greater than that observed in normal (unoperated) neurons. In normal facial neurons, the accumulation of lysine into the nucleus and nucleolus was significantly lower 60 min after morphine administration. However, morphine's inhibition of lysine incorporation was even more pronounced in regenerating neurons. In these cells, nuclear lysine uptake was depressed at 3 and 7 days, while maximum inhibition of cytoplasmic incorporation occurred at 14-days post-axotomy. Morphine administration decreased nucleolar lysine incorporation at all survival intervals.

Prenatal exposure to methadone HCL in relationship to body and brain growth in the rat.

Offspring from methadone-treated Wistar rats (last trimester of pregnancy), as compared to ad lib and pair fed controls, showed a reduction of body growth which continued throughout the 28-day period during which animals were observed after birth. Brain growth, as indicated by weight, cortical thickness and number of cells in the neocortex also showed a reduction in growth, which was apparent only during the first 14 days, after which there were no differences between the groups. However, in the hippocampus, neuronal density changes/unit area continued throughout the 28-day period in the methadone exposed group and to a lesser extent in the PF group suggesting that this area of brain did not return to normal dimensions or degree of maturation by the end of the third week. Since it has been suggested that any deficit in growth associated with prenatalmethadone-exposure might be due to a reduction in food intake, a group pair-fed to the amount of food consumed by the methadone group was included in the study. Generally, the data from the PF group was intermediate between that obtained from the ad lib fed controls and the methadone-exposed animals. Thus, while some of the growth reduction observed in the methadone-exposed pups could have been due to the impaired nutritional status of their mothers during the last third of pregnancy, a part of the reduced growth must be attributed to the drug treatment, since the reduced growth exceeded that observed in the pair-fed group.

Strain differences in the response to morphine on incorporation of 3H-lysine into rat brain protein.

The effect of morphine on the specific activity (SA) of lysine in the plasma free amino acid (FAA) fraction and in the cerebral cortical FAA and protein fractions, as well as on the specific accumulation and incorporation, was determined in male Sprague-Dawley and Wistar rats at various time intervals after intravenous injection of drug and amino acid into unanesthetized animals. The lysine SA was higher in Sprague-Dawley than in Wistar rats in the plasma and brain FAA fraction and in the protein fraction. In the SD strain, morphine decreased the SA of plasma FAA significantly, but had only slight effects in the Wistar strain. In the cortical gray matter, morphine elevated the SA of lysine significantly in both strains, although the rate of decrease of SA with increasing time after injection was different in the two strains. SA of the lysine in cerebral cortical protein increased in both strains with time, but did so more rapidly in the Sprague-Dawley strain. When the data for the free amino acids were expressed in terms of specific accumulation, the observed rates were higher in the Sprague-Dawley animals and reached a point of maximal concentration, which was not observed in animals of the Wistar strain. Morphine elevated the levels of specific accumulation of lysine into the cortical free amino acid pool in both strains of rat. However, specific incorporation of lysine into the cerebral gray cortical protein in control animlas was essentially similar in both strains. Despite the similarity in specific incorporation of lysine into brain protein in both strains of control rat, morphine treatment caused a much more marked inhibition of incorporation of lysine in the Wistar rats. Thus, it is concluded that Sprague-Dawley and Wistar rats are not equivalent in relation to the accumulation of an amino acid in the brain FAA pool from the plasma and that the effect of morphine on specific incorporation of lysine into brain protein is greater in Wistar rats.