Abstract
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.
| Language | English |
|---|---|
| Pages | 117-123 |
| Number of pages | 7 |
| Journal | European Journal of Pharmacology |
| Volume | 434 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 11 Jan 2002 |
Keywords
- (EMG) Electromyogram
- Antipsychotic drug
- Muscarinic receptor antagonist
- Muscle rigidity
- Striatum
ASJC Scopus subject areas
- Pharmacology
Cite this
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Atropine reduces raclopride-induced muscle rigidity by acting in the ventral region of the striatum. / Hemsley, Kim M.; Crocker, Ann D.
In: European Journal of Pharmacology, Vol. 434, No. 3, 11.01.2002, p. 117-123.Research output: Contribution to journal › Article
TY - JOUR
T1 - Atropine reduces raclopride-induced muscle rigidity by acting in the ventral region of the striatum
AU - Hemsley, Kim M.
AU - Crocker, Ann D.
PY - 2002/1/11
Y1 - 2002/1/11
N2 - 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.
AB - 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.
KW - (EMG) Electromyogram
KW - Antipsychotic drug
KW - Muscarinic receptor antagonist
KW - Muscle rigidity
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=0037059431&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(01)01441-8
DO - 10.1016/S0014-2999(01)01441-8
M3 - Article
VL - 434
SP - 117
EP - 123
JO - European Journal of Pharmacology
T2 - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -