B. Tenconi

Perinatal morphine exposure alters peptidergic development in the striatum

It has been reported that perinatal exposure to opiates affects mRNA synthesis, body growth and brain development in mammals, including humans. We have observed that morphine administration in drinking water during the perinatal period alters peptide development in the striatum of the rat. There is a marked increase in substance P and met‐enkephalin content, the latter is maintained even at 30 days postnatally. The transient increase or earlier maturation of substance P content is correlated by a more precocious axon terminal organization as revealed by immunocytochemical staining. The increased metenkephalin content is correlated by a higher abundance of preproenkephalin A mRNA and this correlation is particularly evident at 15 days postnatally. At earlier times both northern blotting and in situ hybridization techniques fail to show any significant difference between control and morphine exposed rats, likely because the peptide content is not very different in the two groups or at least the gap is not as wide as at later times.

Modified ontogenesis of enkephalin and sunstance P containing neurons after perinatal exposure to morphine

The development of met-enkephalin (ME) and substance P (SP) neurons has been studied in rats exposed to morphine during the perinatal period up to day 30 of life. Both peptides levels were measured by specific radioimmunoassays. ME developmental pattern is markedly affected by morphine in the pons-medulla oblongata, while SP does not seem to be influenced. It is suggested that the well known inhibitory effects of opiates on brain growth and maturation might take place by altering the developmental pattern of the endogenous opioid system.

Reactive Sprouting (Pruning Effect) is Altered in the Brain of Rats Perinatally Exposed to Morphine

Recent publications have suggested that the endogenous opioid system may be involved in the natural process of brain growth and development (1). When opioids such as morphine, heroin, or methadone are supplied exogenously to man and laboratory animals, there is a reduced somatic and neuronal development (1, 2, 3, 4). In addition if opioids are added to the culture media of neurons and cell lines, the process of growth and differentiation is altered (3, 4). These effects are apparently mediated by the opioid receptor since the administration of specific antagonists prevents the opioid-induced alterations (3, 4). Also opioid antagonists as naltrexone alter brain and body development when administered to pregnant mothers (1). The diffusion of opiates from the mother blood stream to the fetus brain occurs without apparent difficulties (3, 4). The “opiate foetal syndrome”, encountered in children of mothers addicted to opiates, is apparently becoming widespread with an incidence superior to other neonatal problems such as those caused by alcoholic mothers, or cancer and Down syndrome (3, 4). It is unclear to what extent the brain of neonates from opiate addicted mothers is altered, and furthermore no molecular and cellular clues are available for understanding such damage.

Role of Factors Intrinsic and Extrinsic to CNS Regulating IntraSpinal Degenerative-Atrophy Following Sciatic Nerve Injury

Morphological, immunocytochemical, biochemical and electrophysiological correlates have indicated that the laminae I and II of the spinal cord dorsal horn constitute a complex system playing an important role in endogenous pain control mechanisms (1). The area contains a variety of neuroactive peptides which, as shown by immunocytochemical studies are distintly located in the axon terminals of the peripheral sensory imputs, in a wide population of local interneurons and in the central descending pathways (1,2,3,4,5). Such a complex anatomical organization displays a remarkable capacity of rearrangements. Peripheral nerve lesions cause profound changes in the sensory maps of the dorsal horn (6), suggesting alterations of both sensory imputs and local interneurons. It was, indeed, shown that section of the sciatic nerve induces a significant drop of substance P sensory imput and of met-enkephalin contained in dorsal horn interneurons (5, 7).