Amphetamine-stimulated cortical acetylcholine release: role of the basal forebrain.
Systemic administration of amphetamine results in increases in the release of acetylcholine in the cortex. Basal forebrain mediation of this effect was examined in three experiments using microdialysis in freely-moving rats. Experiment 1 examined whether dopamine receptor activity within the basal forebrain was necessary for amphetamine-induced increase in cortical acetylcholine by examining whether intra-basalis perfusion of dopamine antagonists attenuates this increase. Systemic administration of 2.0 mg/kg amphetamine increased dopamine efflux within the basal forebrain nearly 700% above basal levels. However, the increase in cortical acetylcholine efflux following amphetamine administration was unaffected by intra-basalis perfusions of high concentrations of D1- (100 microM SCH 23390) or D2-like (100 microM sulpiride) dopamine receptor antagonists. Experiments 2 and 3 determined whether glutamatergic or GABAergic local modulation of the excitability of the basal forebrain cholinergic neurons influences the ability of systemic amphetamine to increase cortical acetylcholine efflux. In Experiment 2, perfusion of kynurenate (1.0 mM), a non-selective glutamate receptor antagonist, into the basal forebrain attenuated the increase in cortical acetylcholine produced by amphetamine. Experiment 3 revealed that positive modulation of GABAergic transmission by bilateral intra-basalis infusion of the benzodiazepine receptor agonist chlordiazepoxide (40 microg/hemisphere) also attenuated the amphetamine-stimulated increase in cortical acetylcholine efflux. These data suggest that amphetamine increases cortical acetylcholine release via a complex neuronal network rather than simply increasing basal forebrain D1 or D2 receptor activity.
Department of Psychology, 31 Townshend Hall, The Ohio State University, Columbus, OH 43210, USA.
H M
HM
Arnold
J
J
Fadel
M
M
Sarter
J P
JP
Bruno
D000109:Acetylcholine / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002707:Chlordiazepoxide / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D002707:Chlordiazepoxide; D000661:Amphetamine; D007736:Kynurenic Acid; D000109:Acetylcholine; D004298:Dopamine