Reduction in striatal D2 dopamine receptor mRNA and binding following AF64A lesions.
Unilateral lesions by a cholinotoxin, receptor autoradiography, and in situ hybridization techniques were employed to determine if dopaminergic receptors are located on cholinergic interneurons in the caudate-putamen (CPu). Lesion of the CPu with small amounts of the cholinotoxin AF64A resulted in a significant decrease in D2 receptor mRNA and D2 receptor binding. The loss was more pronounced in lateral and central portions of the CPu. Results obtained using [3H] SCH23390 binding to D1 receptors indicated that there was no change in this dopamine receptor subtype in the AF64A-lesioned CPu. A decrease in D2 receptor mRNA and receptor binding in AF64A-lesioned animals indicates that a population of postsynaptic D2 receptors is associated with the cholinergic interneurons. Lack of any change in [3H]SCH23390 binding in the AF64A-lesioned animals suggests that D1 receptors are not located on cholinergic neurons. These results provide evidence to support the selectivity of the lesion when used as indicated.
Narang
N
N
Neuropsychiatric Research Institute, Fargo, ND 58103.
Pundt
L L
LL
Hunt
M E
ME
Alburges
M E
ME
Wamsley
J K
JK
D000818:Animals; D001345:Autoradiography; D001388:Aziridines / Q000633:toxicity*; D001483:Base Sequence; D001552:Benzazepines / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000031:analogs & derivatives* / Q000633:toxicity; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009466:Neuromuscular Blocking Agents / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism
D001388:Aziridines; D001552:Benzazepines; D009466:Neuromuscular Blocking Agents; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C044894:ethylcholine aziridinium; D002794:Choline