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Amphetamines are among the most widely abused drugs. The user population includes a large proportion of women of child-bearing age. The early ontogeny of the axons in the neocortex and other neural structures positions them to influence the development and connectivity of non-aminergic dendrites and axons in these structures. A cascade of abnormalities in neural circuitry may result from the effects of amphetamines on the dopaminergic system. An attempt has been made to investigate the possible changes in the dopaminergic system in neonatal rats (a human third trimester equivalent model) following chronic D-amphetamine exposure. Neonatal rats were administered 5–15 mg/kg D-amphetamine subcutaneously daily from postnatal day 4 to day 10. Several parameters related to the dopaminergic system were measured. The results showed that tyrosine hydroxylase enzyme levels were significantly decreased in the prefrontal cortex, dorsal striatum and nucleus accumbens. Dopamine D1 receptor (DRD1) levels increased in the dorsal striatum whereas dopamine D2 receptor (DRD2) levels significantly decreased in both the prefrontal cortex and the dorsal striatum but significantly increased in the nucleus accumbens. In order to investigate whether these changes occurred at the transcriptional level, DRD1 and DRD2 mRNAs were detected. The results showed that DRD1 mRNA levels were significantly increased in the dorsal striatum whereas DRD2 mRNA levels were significantly increased in all three brain regions. These results indicate that early D-amphetamine exposure altered the dopaminergic system in the developing rat brain. This change may lead to abnormal perinatal stimulation that may yield long-term consequences.

Dopamine D(1) and D(2) receptor protein expression was examined by Western blotting in newborn infants dying from cerebral asphyxia between 31 and 42 weeks' gestation, and matched controls. Frontal, occipital, temporal, and motor cortex tissue samples were obtained at autopsy (median postmortem interval 35 hours) and frozen for storage at -80 degrees C. A total of 2 immunoreactive bands were detected with each primary antibody in infant brain, whereas a single band was present in adult human and rat tissue. Immunoreactivity varied between cortical areas for both receptors, but their regional patterns differed significantly. D(1) protein levels were higher in motor and temporal cortex than in frontal or occipital cortex. D(2) protein showed graded expression frontal > motor > occipital > temporal cortex. Asphyxia cases showed lower expression of the upper D(2) immunoreactive band, but no difference in regional pattern. Lower D(2) receptor expression may attenuate stress responses and underlie increased vulnerability to hypoxia at birth.