Atropine acts in the ventral striatum to reduce raclopride-induced catalepsy.
While muscarinic receptor antagonists are used to reduce motor side effects associated with the use of antipsychotic drugs, their site of action remains unclear. The study investigated the site of action of the non-selective muscarinic receptor antagonist atropine on catalepsy induced by the selective dopamine D2 receptor antagonist, raclopride. Initially, catalepsy and striatal muscarinic receptor occupancy was assessed 2 h following subcutaneous injection of raclopride and either atropine or vehicle. Catalepsy was significantly reduced by doses of atropine that occupied more than 69% of muscarinic receptors. Next, atropine was injected bilaterally into the ventral striatum, which produced a significant reduction in catalepsy, while injections into the dorsal striatum and substantia nigra had no effect. The site of atropine's action was localised to a discrete area of the ventral striatum through the use of quantitative autoradiographic techniques. These findings provide further evidence for the importance of the ventral striatum in the expression of behaviours.
Alcock
S J
SJ
Department of Clinical Pharmacology and Center for Neuroscience, The Flinders University of South Australia, Bedford Park, Adelaide, South Australia 5042, Australia.
Hemsley
K M
KM
Crocker
A D
AD
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D020891:Raclopride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018727:Muscarinic Antagonists; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D020891:Raclopride; D001285:Atropine