Central catecholaminergic dysfunction and behavioral disorders following hypoxia in adult rats

Abstract

Wistar male rats, 3–4 months old, were made to breathe for 6 h a sub-lethal hypoxic atmosphere consisting of 8% oxygen and 92% nitrogen. Following this treatment, these rats were subjected to a series of behavioral and biochemical tests starting 30 days and ending at about 180 days after the hypoxic insult. An age-matched control group was subjected to the same series of tests. The following findings were made at the time interval indicated, relative to controls: (1) At 30–35 days, diurnal (3 h) and nocturnal (12 h) locomotor activities decreased by about 25%. (2) At 40–45 days, amphetamine in the dose range of 0.25–1 mg/kg proved less effective in eliciting an increase in motor activity and stereotypic behavior. (3) At about 50 days, apomorphine in the dose range 0.25–0.5 mg/kg caused an increase in stereotypic behavior. (4) At 60–65 days, α-methyl- p-tyrosine at the dose of 50 mg/kg caused a more pronounced hypoactive syndrome and a slower rate of recovery of motor activity. (5) At 75–90 days, performance in the active avoidance test was inferior to that of controls. (6) At 180 days, and one hour after a dose of 200 mg/kg α-methyl- p-tyrosine, the turnover rates of hippocampal norepinephrine and caudate-putamen dopamine were much below control. One may tentatively conclude that one of the effects of hypoxia in adult rats is a lesion producing long-term behavioral disorders which are partly ascribed to dopaminergic and, possibly noradrenergic, dysfunction.