Synergistic effects of tetrahydroaminoacridine and lithium on cholinergic function after excitotoxic basal forebrain lesions in rat.
Effects of lithium and tetrahydroaminoacridine (THA), either alone or in combination, were tested in an animal model of excitotoxic cholinergic deafferentation of the cerebral cortex. Rats received ibotenic acid lesions of cholinergic basal forebrain nuclei resulting in a 30% to 40% depletion of both cortical choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity. Lithium as well as THA, given separately either prior or subsequently to the development of the lesion, had small but significant effects on the recovery of cortical ChAT and AChE activity. Applied in combination, these drugs clearly showed synergistic effects. These potentiating actions might be due to neuroprotective/ neurotrophic mechanisms as well as to effects on acetylcholine turnover and muscarinic receptor-coupled phosphoinositide turnover. Similar approaches of combination therapy might prove useful for the management of mental disorders associated with cholinergic dysfunction.
Arendt
T
T
Department of Neuroanatomy, Paul Flechsig Institute of Brain Research, University of Leipzig, Germany. aret@server3.medizin.uni-leipzig.de
Lehmann
K
K
Seeger
G
G
Gärtner
U
U
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007051:Ibotenic Acid / Q000633:toxicity*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D016548:Prosencephalon / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D013619:Tacrine; D008094:Lithium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase