Differential effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptor antagonists applied to the basal forebrain on cortical acetylcholine release and electroencephalogram desynchronization.
It is known that glutamatergic tracts activated from the pedunculopontine tegmentum represent a major input to the nucleus basalis magnocellularis. To establish the role of different ionotropic glutamate receptors in synaptic transmission in the basal forebrain, the pedunculopontine tegmentum was stimulated in urethane-anesthetized rats and the resulting increases in cortical acetylcholine release and desynchronization of the electroencephalogram were monitored. R(-)-3-(2-carboxypiperazine-4-yl)-propyl-I-phosphonic acid (CPP), an antagonist at N-methyl-D-aspartate-type glutamate receptors, and 6, 7-dinitroquinoxaline-2, 3-dione (DNQX), an antagonist at alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors, were delivered through a microdialysis probe placed in the basal forebrain. The N-methyl-D-aspartate antagonist preferentially inhibited cortical acetylcholine release, while the AMPA antagonist was more powerful in reducing desynchronization. A combination of both N-methyl-D-aspartate and AMPA antagonists abolished the increase in cortical acetylcholine release without reducing desynchronization. The dissociation between increased cortical acetylcholine release and electroencephalogram desynchronization suggests that the activity of corticopetal basal forebrain cholinergic neurons is neither necessary nor sufficient to produce electroencephalogram desynchronization. Rather, the nucleus basalis can probably affect the electroencephalogram by its projections to the thalamus. The reversal of the inhibitory effect of DNQX on the electroencephalogram by CPP may be due to the blockade of N-methyl-D-aspartate receptors on the GABAergic projection from the basal forebrain to the thalamus.
Rasmusson
D D
DD
Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.
Szerb
I C
IC
Jordan
J L
JL
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003344:Cortical Synchronization / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D010879:Piperazines / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C056723:FG 9041; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D000109:Acetylcholine