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 exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC) were evaluated in the substantia nigra (SN) of male and female rats, at three postnatal ages (PD21, PD30 and PD70), by immunohistochemical detection of tyrosine hydroxylase (TH) in dopaminergic neurons and of glial fibrillary acidic protein (GFAP) in astrocytes. Our results showed that the effects of pre- and perinatal exposure to Delta(9)-THC on neuronal and astroglial immunoreactivities in the SN (compacta and reticulata) varied with sex, with male rats being more susceptible than females. Prenatal exposure to Delta(9)-THC decreased TH immunoreactivity 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 expression decreased with age in Delta(9)-THC-exposed males in the SNc pars compacta, whereas it increased in controls. On the contrary, TH expression was maintained stable in the SN pars compacta of Delta(9)-THC-exposed females from PD21. These differences in neuronal development caused by prenatal Delta(9)-THC exposure were associated with significant differences in GFAP expression by astroglial cells in both sexes. On PD21, GFAP immunoreactivity decreased in the SN in Delta(9)-THC-exposed male rats. Although GFAP expression increased in Delta(9)-THC-exposed males with age, it did not reach control levels by PD70. On the contrary, significantly increased GFAP expression in the Delta(9)-THC-exposed females on PD21 was observed, compared to their controls and also to Delta(9)-THC-exposed male rats; however, the GFAP expression shown by Delta(9)-THC-exposed females stabilized from PD21. These Delta(9)-THC-induced changes in the glial development could indicate that Delta(9)-THC accelerated the maturation of astrocytes in female rats, whereas Delta(9)-THC delayed astrocytic maturation in Delta(9)-THC-exposed males. These findings suggest that pre- and perinatal exposure to Delta(9)-THC can lead to long-term effects in both neurons and glial cells.