TY - JOUR
T1 - Differential effects of antipsychotics on haloperidol-induced vacuous chewing movements and subcortical gene expression in the rat
AU - McCullumsmith, Robert E.
AU - Stincic, Todd L.
AU - Agrawal, Smriti M.
AU - Meador-Woodruff, James H.
N1 - Funding Information:
This work was supported by a grant from Lilly Research Laboratories, Eli Lilly and Company. The authors thank Alan Hogg and Pat Smolarski for their technical assistance.
PY - 2003/9/12
Y1 - 2003/9/12
N2 - The behavioral and neurochemical effects of switching from typical to atypical medications have not been evaluated in the rodent models of tardive dyskinesia. Thus, we treated rats with haloperidol-decanoate for 12 weeks, and assessed the effects of additional treatment with olanzapine, haloperidol, clozapine, or vehicle on vacuous chewing movements and expression of transcripts for dopamine receptors, tyrosine hydroxylase, δ-opioid receptor, prodynorphin, preproenkephalin, glutamic acid decarboxylase-65 (glutamic acid decarboxylase (GAD)-65) and GAD-67 and N-methyl-D-aspartate (NMDA) receptor subunits in the striatum and its efferent pathways. Haloperidol-decanoate induced vacuous chewing movements extinguished following an additional 4 weeks of treatment with vehicle, olanzapine or haloperidol, but not clozapine. Post-treatment, vacuous chewing movements in the clozapine group were significantly higher than the vehicle, olanzapine and haloperidol groups. GAD-67 mRNA expression in the globus pallidus was decreased following additional treatment with olanzapine or haloperidol, but not clozapine. Changes in expression of other transcripts were not detected. These findings demonstrate important differences in the effects of typical and atypical antipsychotics on chronic vacuous chewing movements.
AB - The behavioral and neurochemical effects of switching from typical to atypical medications have not been evaluated in the rodent models of tardive dyskinesia. Thus, we treated rats with haloperidol-decanoate for 12 weeks, and assessed the effects of additional treatment with olanzapine, haloperidol, clozapine, or vehicle on vacuous chewing movements and expression of transcripts for dopamine receptors, tyrosine hydroxylase, δ-opioid receptor, prodynorphin, preproenkephalin, glutamic acid decarboxylase-65 (glutamic acid decarboxylase (GAD)-65) and GAD-67 and N-methyl-D-aspartate (NMDA) receptor subunits in the striatum and its efferent pathways. Haloperidol-decanoate induced vacuous chewing movements extinguished following an additional 4 weeks of treatment with vehicle, olanzapine or haloperidol, but not clozapine. Post-treatment, vacuous chewing movements in the clozapine group were significantly higher than the vehicle, olanzapine and haloperidol groups. GAD-67 mRNA expression in the globus pallidus was decreased following additional treatment with olanzapine or haloperidol, but not clozapine. Changes in expression of other transcripts were not detected. These findings demonstrate important differences in the effects of typical and atypical antipsychotics on chronic vacuous chewing movements.
KW - Clozapine
KW - Haloperidol
KW - Neuroleptic
KW - Olanzapine
KW - Oral dyskinesia
KW - Striatum
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U2 - 10.1016/j.ejphar.2003.08.018
DO - 10.1016/j.ejphar.2003.08.018
M3 - Article
C2 - 14519413
AN - SCOPUS:1642308000
SN - 0014-2999
VL - 477
SP - 101
EP - 112
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -