High opioid doses inhibit whereas low doses enhance neuritogenesis in PC12 cells

Abstract

Exposure to opiates affects brain development, cell growth as well as in vitro cell differentiation. Perinatal treatment with morphine has been reported to impair neuronal plasticity after neonatal lesion with 5,7-dihydroxytryptamine (5,7-DHT). This study has investigated the use of μ, δ and k opioid receptor ligands to examine the selective receptor mediated inhibition of PC12 neurite formation. Morphine and d-Ala 2, d-Leu 5-enkephalin (DADLE) had a comparable inhibitory potency with a maximal effect at 1 mM concentration, while both naltrexone and naltrindole antagonized their effect at only 10 nM. d-Ala 2-MePhe 4,Gly-ol 5-enkephalin (DAMGO) showed only a transient inhibitory effect. The administration of 10 nM guanosine 5′- O-(3-thiotriphosphate) (GTP-γ-S) prevented morphine inhibition. It is suggested that opiate inhibition of neuritogenesis may be mediated by a receptor with δ-like characteristics coupled to G proteins. On the other hand, the activation of this receptor with morphine at a very low concentration (1 pM) actually enhanced nerve growth factor (NGF) neurite promoting activity.