EEDQ reduces the striatal neurotensin mRNA response to haloperidol.
Haloperidol is believed to induce neurotensin/neuromedin N (NT/ N) gene expression in the dorsolateral striatum (DLST) of the rat brain via dopamine D2 receptor blockade, but is also known to interact with other receptors as well. To further characterize haloperidol's effects, rats were treated with the irreversible monoaminergic receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2 hydroxyquinolone (EEDQ). In situ hybridization was performed for NT/N mRNA. D2-like and sigma receptor autoradiography was performed using 125I-sulpride and 3H-1,3-di-o-tolylguanidine (DTG), respectively. Despite antagonism of D2 receptors, pretreatment with EEDQ failed to significantly reduce the NT/N mRNA response when given 3 days prior to the haloperidol challenge. These data suggest that the acute effects of haloperidol on NT/N mRNA expression in large part result from D2 receptor antagonism. Nonetheless, a contribution of other receptors can not be excluded.
Adams
M R
MR
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Dobie
D J
DJ
Merchant
K M
KM
Unis
A
A
Dorsa
D M
DM
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009496:Neurotensin / Q000235:genetics*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D011804:Quinolines; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; D009496:Neurotensin; C000470:EEDQ; D006220:Haloperidol