Perinatal morphine exposure alters peptidergic development in the striatum

Abstract

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.

Perinatal morphine II: Changes in cortical plasticity

“…After weaning, the opiate dosage to the pups, now separated from their mothers, was markedly reduced, but no signs of withdrawal such as respiratory depression were observed. As reported previously, body growth was reduced by 20% in animals perinatally exposed to morphine (Tenconi et al, 1992). cortex was similar among all the experimental groups at 7 days; however, it was significantly higher in the salinetreated lesioned animals at 8 weeks of life (Figs.…”

“…These data suggest the direct or indirect implication of the endogenous opioid system in the modulation of growth and development of the nervous system. Previous studies performed in our laboratory showed that perinatal exposure to morphine affects met-enkephalin (ME) and substance P (SP) innervation of the striatum (Tenconi et al, 1992). The peptidergic changes occur also in other brain areas and are accompanied by reduced expression of synapsin I mRNA, suggesting that perinatal morphine treatment affects synaptic development and maturation in the brain (Di Giulio et al, 1995).…”

“…The peptidergic changes occur also in other brain areas and are accompanied by reduced expression of synapsin I mRNA, suggesting that perinatal morphine treatment affects synaptic development and maturation in the brain (Di Giulio et al, 1995). These alterations are reversible with time (Tenconi et al, 1992;Di Giulio et al, 1995) and might not be entirely responsible for the behavioral deficits induced by prenatal opiate exposure (Wilson et al, 1979;Hans et al, 1984). We further examined the effects of opioids on the nervous system by monitoring reactive plasticity of injured neurons following selective lesion of neuronal pathways, Cerebral cortex and spinal cord were depleted of serotonin by means of 5,7-DHT (5,7-dihydroxytryptamine) neonatal intraperitoneal administration; the degenerative process is followed by a gradual recovery of serotonin (5-HT) levels in the denervated areas, which is preceded by a transient 5-HT hyperinnervation of pons-medulla (Gorio et al, 1993).…”

Perinatal morphine treatment inhibits pruning effect and regeneration of serotoninergic pathways following neonatal 5,7‐HT lesions

“…The amount of morphine drunk by the single pups was smaller, but no signs of withdraw1 were observed. We also monitored body growth, which declined in the morphine groups by about 20 percent, confirming the detailed report of Tenconi et al (1992).…”

Glycosaminoglycans in nerve injury: II. Effects on transganglionic degeneration and on the expression of neurotrophic factors

“…and perfused with 4% paraformaldehyde-0.5% glutaraldehyde mixture, then the lumbar cord was dissected out postfixed overnight with the same fixative. Specimens were then sectioned with a Cambridge vibratome and stained following procedures previously published (Di Giulio et al, 1985, 1989.The oligonucleotide complementary of pre-proenkephalin (NEP 502) was labelled at the 3' end with terminal deoxynucleotidyl transferase, as was previously described (Tenconi et al, 1992). For the neurotrophin in situ hybridization studies, we used cDNA probes corresponding to the 0.77 kb fragment of the rat gene for NGF, that was subcloned at the Sma I site of pBluescript (M13 +); and cDNA probes corresponding to the 3.4 kb fragment of the rat gene for p75 fast NGFR subcloned at EcoR I-Hind 111 sites of pUC19.…”