Nimodipine prevents the in vivo decrease in hippocampal extracellular acetylcholine produced by hypobaric hypoxia.
Hypoxia decreases acetylcholine (ACh) synthesis and release in vitro, and ACh synthesis in vivo; however, its effect on extracellular concentration of ACh in vivo is not known. The calcium channel blocker nimodipine is a cerebrovascular dilator which also increases extracellular ACh in vivo. Therefore, it may provide protection from the effects of hypobaric hypoxia on the cholinergic system either via its effects on vascular function or by direct action on the nervous system. This study examined the effect of hypobaric hypoxia on extracellular ACh and choline levels, as measured by microdialysis, as well as the effects of nimodipine under hypoxia. Microdialysis guide cannulae were implanted into the hippocampal region of male Fischer rats so that probes would sample from the CA1 and DG regions. Animals were then exposed for eight hours to a simulated altitude of 5,500 m (18,000 ft) or tested at sea level for an equivalent duration. HPLC with electrochemical detection was used for analysis of the dialysates. At 5,500 m extracellular ACh levels in the placebo-treated group were significantly lower than the sea level group values. This decrement was reversed by nimodipine administered i.p. immediately preceding altitude ascent (10 mg/kg) and 250 min post-altitude ascent (10 mg/kg). These data suggest that nimodipine may provide protection from the detrimental effects of hypoxia on hippocampal cholinergic function.
Shukitt-Hale
B
B
Military Performance and Neuroscience Division, United States Army Research Institute of Environmental Medicine, Natick, MA 01760-5007.
Stillman
M J
MJ
Levy
A
A
Devine
J A
JA
Lieberman
H R
HR
D000109:Acetylcholine / Q000378:metabolism*; D000532:Altitude Sickness / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D009553:Nimodipine; D000109:Acetylcholine