Persistent alteration of rat brain monoamine levels by carbon monoxide exposure: sex differences and behavioral...

Adult rats of both sexes were exposed to carbon monoxide (CO) at 0.42% in a continuous flow of air. Exposures were terminated at the physiologic endpoint of extreme respiratory distress. Following behavioral testing, 4-6 weeks after exposure, the rats were sacrificed and brain regions were analysed for monoamine content. In frontal cortex dopamine (DA) was increased in both sexes following CO and was correlated with motor activity in the CO-exposed rats but not in controls. Both sexes showed an increase in norepinephrine (NE) in the striatum although not correlated with motor activity. Female rats also were found to have reductions in striatal DA as well as NE and 5-hydroxytryptamine (5-HT) in both midbrain and pons medulla samples. In male control animals motor activity was generally correlated with NE and 5-HT levels in cortex, midbrain and pons-medulla. Exposure to CO disrupted these correlations in all areas. Female controls showed correlations between motor activity and NE in cortex and pons-medulla and DA in striatum and pons-medulla. Exposure to CO also altered this pattern with correlations to DA appearing in cortex and midbrain. A hypothesis is presented which suggests that the degree and persistence of behavioral changes from neurotoxic exposures is related to reductions in redundant control mechanisms resulting from generalized cellular damage in the brain. This permits the expression of the behavioral modality linked to damage to one or more specific neurotransmitter systems depending upon the individual vulnerability of these systems.