Dopamine depletion attenuates amphetamine-induced increases of cortical acetylcholine release.
The extent to which the d-amphetamine (2.0 mg/kg)-induced increase in cortical acetylcholine release is mediated by dopamine and/or noradrenaline was assessed using in vivo microdialysis in freely moving rats. Unilateral 6-hydroxydopamine lesions of the mesotelencephalic dopaminergic system, which depleted forebrain dopamine by 99% on the lesioned side, significantly attenuated the effect of d-amphetamine on cortical acetylcholine release compared to a surgical control group (160% baseline vs. 270%), suggesting that dopamine at least in part mediates this effect of d-amphetamine. In contrast, bilateral 6-hydroxydopamine lesions of the dorsal noradrenergic bundle which depleted forebrain noradrenaline by at least 95% had no effect on d-amphetamine-stimulated cortical acetylcholine release. These results point to an important role for forebrain dopamine in the regulation of cortically projecting cholinergic neurons and fail to support the hypothesis that the ascending noradrenergic projections of the locus coeruleus are significantly involved.
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
J C
JC
Day
C S
CS
Tham
H C
HC
Fibiger
D000109:Acetylcholine / Q000378:metabolism*; D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism
D012701:Serotonin; D016627:Oxidopamine; D000661:Amphetamine; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine