Enhancement of hippocampal cholinergic neurotransmission through 5-HT1A receptor-mediated pathways by repeated lithium treatment in rats.
Hippocampal cholinergic neuronal activity is reported to be regulated, at least partly, through serotonin1A (5-HT1A) receptors. Chronic lithium treatment has been shown to alter both behavioral and neurochemical responses mediated by postsynaptic 5-HT1A receptors. We investigated whether long-term lithium treatment affects central cholinergic neurotransmission through 5-HT1A receptor-mediated pathways. Changes in acetylcholine (ACh) release induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, in the rat hippocampus were measured using a microdialysis technique and a radioimmunoassay for ACh. Administration of lithium for 21 days resulted in a serum lithium concentration of 1.03 mM and caused little change in density or affinity of [3H]8-OH-DPAT binding sites in the hippocampus. The local application of 8-OH-DPAT into the hippocampus of lithium treated rats increased the ACh efflux in both the absence and the presence of physostigmine, a cholinesterase (ChE) inhibitor, in the perfusion fluid. The basal ACh efflux of lithium treated rats was not different from that of the control rats under normal conditions, but was significantly higher than that of the controls when ChE was inhibited. These results demonstrate that chronic lithium treatment increases spontaneous ACh release in the hippocampus under conditions of ChE inhibition, but not under normal conditions, and enhances cholinergic neurotransmission through 5-HT1A receptor-mediated pathways, and suggest that activation of 5-HT1A receptor function by lithium is related to the enhancement of hippocampal cholinergic neurotransmission.
Fujii
T
T
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Nakai
K
K
Nakajima
Y
Y
Kawashima
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004032:Diet; D006624:Hippocampus / Q000502:physiology*; D008094:Lithium / Q000097:blood / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D002800:Cholinesterase Inhibitors; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008094:Lithium; D010830:Physostigmine; D000109:Acetylcholine