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.

Severe chronic alcohol misuse leads to neuropathological changes in human brain, with the greatest neuronal loss in the dorsolateral prefrontal cortex. In this region, GABA_A receptors are selectively upregulated, and show altered subunit expression profiles only in alcoholics without comorbid disease, whereas glutamate_NMDA subunit expression profiles are selectively downregulated only in alcoholics with comorbid cirrhosis of the liver. To determine whether these outcomes might be conditional on synaptic transmitter levels, evoked release was studied in well-characterized synaptosome suspensions preloaded with L-[³H]glutamate and [¹⁴C]GABA and stimulated electrically (±10 V contiguous square waves, 0.4 ms, 100 Hz, 1.5 min) with and without Ca²⁺. Stimulation elicited brief peaks of both radioisotopes that were larger in the presence of Ca²⁺ ions (p < 0.01). A repeat stimulus evoked a second, smaller (p < 0.01) peak. Ca²⁺-dependent L-[³H]glutamate release, but not [¹⁴C]GABA release, was higher overall in alcoholics than in controls (p < 0.05). With comorbid cirrhosis, L-[³H]glutamate release showed a graded response, whereas [¹⁴C]GABA release was lowest in noncirrhotic alcoholics. Release patterns did not differ between cortical regions, or between males and females. Neither age nor postmortem interval was a significant confounder. The released transmitters may differentially alter receptor profiles on postsynaptic cells.

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