Electroencephalographic activation by tacrine, deprenyl, and quipazine: cholinergic vs. non-cholinergic contributions.
Drugs that stimulate central cholinergic transmission can induce activated, high frequency electroencephalographic (EEG) activity in rats. Monoaminergic enhancement also produces EEG activation, either by a direct stimulation of monoaminergic transmission in cortex, or a transsynaptic excitation of cholinergic projection neurons receiving excitatory monoaminergic afferents. We examined the degree of cholinergic involvement in EEG activation produced by monoaminergic and cholinergic drugs in rats. All animals were pretreated with 10 mg/kg reserpine and either 1 or 5 mg/kg scopolamine to abolish EEG activation. The acetylcholinesterase inhibitor tacrine (5-20 mg/kg) restored EEG activation in the low dose scopolamine group, but was less effective against the high scopolamine dose. The monoamine oxidase inhibitor deprenyl and the serotonergic receptor agonist quipazine restored EEG activation, an effect that was largely unaffected by different scopolamine doses. These results confirm that tacrine produces EEG activation by means of cholinergic stimulation. In contrast, activation produced by deprenyl or quipazine does not appear to be mediated by a transsynaptic excitation of cholinergic neurons and likely depends on a direct enhancement of cortical monoaminergic neurotransmission.
Dringenberg
Hans C
HC
Department of Psychology, Queen's University, K7L 3N6, Kingston, Ontario, Canada. dringenb@psyc.queensu.ca
Rubenstein
Megan L
ML
Solty
Heidi
H
Tomaszek
Summer
S
Bruce
Alanna
A
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004569:Electroencephalography; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D016548:Prosencephalon / Q000378:metabolism* / Q000503:physiopathology; D011814:Quipazine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012110:Reserpine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013619:Tacrine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D018727:Muscarinic Antagonists; D012702:Serotonin Antagonists; D012642:Selegiline; D013619:Tacrine; D011814:Quipazine; D012110:Reserpine; D012601:Scopolamine; D000109:Acetylcholine