Memantine attenuates the increase in striatal preproenkephalin mRNA expression and development of haloperidol-induced persistent oral dyskinesias in rats.
Tardive dyskinesia (TD) is a serious motor side effect of long-term neuroleptic treatment that may persist after drug withdrawal. Alterations in striatal enkephalinergic neurons due to excessive glutamatergic activity is a possible pathogenetic mechanism. We studied the effect of the NMDA antagonist memantine in a rat model of TD, in which vacuous chewing movements (VCM) were induced by 20 weeks of haloperidol administration. The striatal density of preproenkephalin mRNA was measured and the number of neurons estimated. Haloperidol induced persistent VCM that was associated with increased striatal expression of preproenkephalin mRNA. Memantine inhibited the development of haloperidol-induced persistent VCM and attenuated the increase in preproenkephalin mRNA expression. This suggests that glutamate-mediated up-regulation of striatal enkephalin plays a role in the development of haloperidol-induced persistent oral dyskinesias.
Andreassen
Ole A
OA
Department of Psychiatry, University of Oslo and Ullevål University Hospital, Kirkeveien 166, 0407 Oslo, Norway. o.a.andreassen@psykiatri.uio.no
Waage
Jo
J
Finsen
Bente
B
Jørgensen
Hugo A
HA
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000009:adverse effects; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004745:Enkephalins / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000037:antagonists & inhibitors*; D017403:In Situ Hybridization; D008409:Mastication / Q000187:drug effects; D008559:Memantine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior; D013997:Time Factors
D018492:Dopamine Antagonists; D004745:Enkephalins; D018691:Excitatory Amino Acid Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; C033660:preproenkephalin; D006220:Haloperidol; D008559:Memantine