AF64A lesions of mouse striatum result in ipsilateral rotations to D2 dopamine agonists but contralateral rotations to muscarinic cholinergic agonists.
Behavioral and anatomical evidence supports an interaction between the dopaminergic and cholinergic systems in regulating certain behavioral conditions and motor functions. In this study, we utilized the cholinotoxin, acetylethylcholine mustard aziridinium ion (AF64A), to lesion the mouse corpus striatum in order to examine the role of cholinergic interneurons in striatum on cholinergic- and dopaminergic-mediated rotational behavior. Mice were unilaterally lesioned with AF64A and then challenged with a variety of dopaminergic and cholinergic agonists and antagonists. The results show that mice with AF64A-induced lesions rotate ipsilaterally to challenge doses of the dopamine agonists, apomorphine and pergolide, but rotate contralaterally to challenge injections of the cholinergic agonist, oxotremorine. The gamma aminobutyric acid (GABA) agonist, muscimol, and the M1 agonist, (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride failed to elicit rotational behavior. The D1 dopamine receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride, inhibited rotations induced by apomorphine at concentrations 10-fold lower than those needed to block the effects of pergolide. However, the D2 dopamine receptor antagonist, sulpiride, blocked pergolide-induced rotations at concentrations about 4-fold lower than those needed to inhibit apomorphine-induced rotational behavior. Atropine blocked oxotremorine-induced contralateral rotations but enhanced apomorphine- and pergolide-induced ipsilateral rotations induced in AF64A-lesioned mice. Atropine was 10 times more effective in blocking oxotremorine-induced rotations than was the M3 antagonist, 4-diphenylacetoxy-N-methyl piperidine methiodide, and was 100 times more potent than the M2 and M1 antagonist, N,N'-bis[6-[[(2- methoxyphenyl)methyl]amino]hexyl]-1,8-octanediamine tetrahydrochloride, or the M1 antagonist, pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhou
L W
LW
Department of Pharmacology, Medical College of Pennsylvania/EPPI, Philadelphia.
Zhang
S P
SP
Connell
T A
TA
Weiss
B
B
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001388:Aziridines / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D007839:Functional Laterality; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D010095:Oxotremorine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010479:Pergolide / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012399:Rotation; D013469:Sulpiride / Q000494:pharmacology
D001388:Aziridines; D001552:Benzazepines; D015259:Dopamine Agents; D009466:Neuromuscular Blocking Agents; D010277:Parasympathomimetics; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D010479:Pergolide; D010095:Oxotremorine; D001285:Atropine; D013469:Sulpiride; C044894:ethylcholine aziridinium; D001058:Apomorphine; D002794:Choline