Neuronal and astroglial response to pre- and perinatal exposure to delta-9-tetra-hydrocannabinol in the rat substantia nigra

The responses of neurons and astroglial cells to pre- and perinatal exposur e to Delta(9)-tetrahydrocannabinol (Delta(9)-THC) were evaluated in the sub stantia nigra (SN) of male and female rats, at three postnatal ages (PD21, PD30 and PD70), by immunohistochemical detection of tyrosine hydroxylase (T H) in dopaminergic neurons and of glial fibrillary acidic protein (GFAP) in astrocytes. Our results showed that the effects of pre- and perinatal expo sure to Delta(9)-THC on neuronal and astroglial immunoreactivities in the S N (compacta and reticulata) varied with sex, with male rats being more susc eptible than females. Prenatal exposure to Delta(9)-THC decreased TH immuno reactivity in the SN of males on PD21 when compared to both their controls and Delta(9)-THC-exposed females of the same age. Furthermore, the TH expre ssion decreased with age in Delta(9)-THC-exposed males in the SNc pars comp acta, whereas it increased in controls. On the contrary, TH expression was maintained stable in the SN pars compacta of Delta(9)-THC-exposed females f rom PD21. These differences in neuronal development caused by prenatal Delt a(9)-THC exposure were associated with significant differences in GFAP expr ession by astroglial cells in both sexes. On PD21, GFAP immunoreactivity de creased in the SN in Delta(9)-THC-exposed male rats. Although GFAP expressi on increased in Delta(9)-THC-exposed males with age, it did not reach contr ol levels by PD70. On the contrary, significantly increased GFAP expression in the Delta(9)-THC-exposed females on PD21 was observed, compared to thei r controls and also to Delta(9)-THC-exposed male rats; however, the GFAP ex pression shown by Delta(9)-THC-exposed females stabilized from PD21. These Delta(9)-THC induced changes in the glial development could indicate that D elta(9)-THC accelerated the maturation of astrocytes in female rats, wherea s Delta(9)-THC delayed astrocytic maturation in Delta(9)-THC-exposed males. These findings suggest that pre- and perinatal exposure to Delta(9)-THC ca n lead to long-term effects in both neurons and glial cells. Copyright (C) 2000 S. Karger AG, Basel.