Production of panic-like symptoms by lactate is associated with increased neural firing and oxidation of brain redox in the rat hippocampus.
Lactate uses an unknown mechanism to induce panic attacks in people and panic-like symptoms in rodents. We tested whether intraperitoneal (IP) lactate injections act peripherally or centrally to induce panic-like symptoms in rats by examining whether IP lactate directly affects the CNS. In Long-Evans rats, IP lactate (2 mmol/kg) injection increased lactate levels in the plasma and the cerebrospinal fluid. IP lactate also induced tachycardia and behavioral freezing suggesting the production of panic-like behavior. To enter intermediate metabolism, lactate is oxidized by lactate dehydrogenase (LDH) to pyruvate with co-reduction of NAD(+) to NADH. Therefore, we measured the ratio of NADH/NAD(+) to test whether IP lactate altered lactate metabolism in the CNS. Lactate metabolism was studied in the hippocampus, a brain region believed to contribute to panic-like symptoms. IP lactate injection lowered the ratio of NADH/NAD(+) without altering the total amount of NADH and NAD(+) suggesting oxidation of hippocampal redox state. Lactate oxidized hippocampal redox since intrahippocampal injection of the LDH inhibitor, oxamate (50mM) prevented the oxidation of NADH/NAD(+) by IP lactate. In addition to oxidizing hippocampal redox, IP lactate rapidly increased the firing rate of hippocampal neurons. Similar IP pyruvate injections had no effect. Neural discharge also increased following intrahippocampal lactate injection suggesting that increased discharge was a direct action of lactate on the hippocampus. These studies show that oxidation of brain redox and increased hippocampal firing are direct actions of lactate on the CNS that may contribute to the production of lactate-induced panic.
Bergold
Peter J
PJ
Department of Physiology and Pharmacology, SUNY-Downstate Medical Center, Brooklyn, NY 11203, United States. pbergold@downstate.edu
Pinkhasova
Valariya
V
Syed
Maryam
M
Kao
Hsin-Yi
HY
Jozwicka
Anna
A
Zhao
Ning
N
Coplan
Jeremy D
JD
Dow-Edwards
Diana
D
Fenton
André A
AA
D000200:Action Potentials; D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D007267:Injections; D007773:Lactates / Q000097:blood*; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D010084:Oxidation-Reduction; D016584:Panic Disorder / Q000378:metabolism* / Q000503:physiopathology*; D019289:Pyruvic Acid / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D019354:Sodium Lactate / Q000494:pharmacology
D007773:Lactates; D009243:NAD; D019289:Pyruvic Acid; D019354:Sodium Lactate