Atropine reduces raclopride-induced muscle rigidity by acting in the ventral region of the striatum.
Parkinson-like extrapyramidal motor side effects associated with the use of antipsychotic drugs, such as increased muscle rigidity, are thought to result from blockade of striatal dopamine D2 receptors. While anticholinergic medications (muscarinic receptor antagonists) ameliorate extrapyramidal side effects, the mechanisms underlying their effectiveness remain unclear. We investigated the site of action of atropine, a non-selective muscarinic receptor antagonist, in reducing increased muscle rigidity, assessed as increases in tonic electromyographic (EMG) activity, induced by the selective dopamine D2 receptor antagonist, raclopride. Atropine significantly reduced raclopride-induced EMG increases in rat hindlimb muscles, when injected into the ventral striatum, but not the dorsal striatum or the substantia nigra. Atropine's site of action was localised to a small area of muscarinic receptors within the ventral part of the striatum, using quantitative autoradiography. These findings provide new information about the regulation of motor control by muscarinic receptor antagonists and additional evidence about the functional heterogeneity of the striatum.
Hemsley
Kim M
KM
Department of Clinical Pharmacology and Centre for Neuroscience, The Flinders University of South Australia, Bedford Park, South Australia 5042, Australia.
Crocker
Ann D
AD
D000818:Animals; D001285:Atropine / Q000627:therapeutic use*; D001479:Basal Ganglia / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D018492:Dopamine Antagonists / Q000009:adverse effects; D065127:Dopamine D2 Receptor Antagonists; D004576:Electromyography / Q000187:drug effects; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D009127:Muscle Rigidity / Q000139:chemically induced* / Q000517:prevention & control*; D020891:Raclopride / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013997:Time Factors
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018727:Muscarinic Antagonists; D017448:Receptors, Dopamine D2; D020891:Raclopride; D001285:Atropine