Effect of normobaric hyperoxia on two indexes of synaptic function in Fisher 344 rats.
The physiological response of two central nervous system neurotransmitter receptors to oxidative stress was studied using the rat model of hyperoxia. We show that hyperoxia leads to a decline in the ability of isoproterenol (ISO) to augment GABAergic responses in cerebellar Purkinje neurons in vivo. This effect is reversed by the N-tert-butylalpha-phenylnitrone (PBN). We also show that hyperoxia produces a decline in the ability of oxotremorine (OXO) to stimulate dopamine (DA) release in striatal slices. This effect is accompanied by an increase in hydroxyl radical levels in the CNS reflected in an increase in 2,3-DHBA, suggesting that the change is the result of an increased level of oxidative stress. We also show a time dependent effect of hyperoxia on both beta-adrenergic and muscarinic receptor function. We examined the interaction between age and hyperoxia exposure and found that in 12-month-old rats there is a decline in the baseline response prior to oxygen exposure that may interfere with observing a subsequent effect of hyperoxia. Differential effects were observed between the cerebellum and striatum with respect to the interaction of age and time of oxygen exposure. Overall, the data suggest that age and hyperoxia may be acting via a common mechanism because there was no synergistic effect of the two conditions.
Bickford
P C
PC
Department of Pharmacology, University of Colorado Health Sciences Center, Department of Veterans Affairs Medical Center, Denver, 80262, USA. Paula.Bickford@uchsc.edu
Chadman
K
K
Williams
B
B
Shukitt-Hale
B
B
Holmes
D
D
Taglialatela
G
G
Joseph
J
J
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D018496:Hyperoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010095:Oxotremorine / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D017665:Hydroxyl Radical; D005680:gamma-Aminobutyric Acid; D010095:Oxotremorine; D007545:Isoproterenol; D004298:Dopamine