Perinatal morphine treatment inhibits pruning effect and regeneration of serotoninergic pathways following neonatal 5,7-HT lesions.
Lesion of the serotoninergic system in neonate rats is an ideal model for assessing the activity of chemical substances capable of affecting neuronal plasticity and regeneration (Jonsson et al., Dev Brain Res 16: 171-180, 1984). Treatment of newborn rats within 6 hr from birth with the selective neurotoxin 5,7-dihydroxytryptamine causes degeneration of the most distal serotoninergic axons. In our experimental conditions we have observed that after such neurotoxic treatment there is spinal cord denervation, which is particularly remarkable in the lumbar segment. This degenerative event is followed by gradual regeneration of the lesioned axons, with good reinnervation of the entire cord within 8 weeks. The degeneration-regeneration process is correlated with a transient hyperinnervation of the pons-medulla and hypothalamus by the short collaterals (pruning effect), as evidenced by increased serotonin content. Perinatal morphine exposure markedly impairs serotonin regeneration in the spinal cord. In addition, opiate treated rats are more susceptible to lesions, as shown by the neurotoxin induced denervation of the cortex, pons-medulla, and hypothalamus, which does not occur in lesioned controls. Therefore, our observations suggest that perinatal exposure to morphine affects the plasticity and regeneration of the developing serotoninergic system by increasing its susceptibility to neurotoxic lesions and reducing its regenerative capacity.
Gorio
A
A
Department of Medical Pharmacology, Faculty of Medicine, University of Milano, Italy.
Di Giulio
A M
AM
Germani
E
E
Bendotti
C
C
Bertelli
A
A
Mantegazza
P
P
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D013462:Sulfur Radioisotopes
D013462:Sulfur Radioisotopes; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D009271:Naltrexone; D009020:Morphine