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.