Journal article
D-2 DOPAMINE-RECEPTOR ANTISENSE OLIGODEOXYNUCLEOTIDE INHIBITS THE SYNTHESIS OF A FUNCTIONAL POOL OF D-2 DOPAMINE-RECEPTORS
Molecular pharmacology, v 48(4), pp 730-737
01 Oct 1995
PMID: 7476901
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In vivo administration of an antisense oligonucleotide targeted toward the D-2 dopamine (DA) receptor mRNA (D-2 AS) markedly inhibited D-2 receptor-mediated behaviors but produced only a relatively small reduction in the levels of D-2 DA receptors in mouse striatum. This apparent dissociation between DA receptor-mediated behaviors and the levels of D-2 DA receptors was addressed by inhibiting the total number of D-2 DA receptors by intraperitoneal administration of the selective, irreversibly acting D-2 DA receptor antagonist fluphenazine-N-mustard (FNM) and then determining the effects of D-2 AS, administered intracerebroventricularly, on the rate of synthesis of D-2 DA receptors and on the recovery of D-2 receptor-mediated behaviors. FNM inactivated similar to 90% of D-2 DA receptors within 4 hr of treatment, after which the receptors returned to normal levels by similar to 8 days. D-2 AS treatment significantly inhibited the rate of recovery of D-2 DA receptors in striatum of FNM-treated mice. FNM treatment also produced a number of behavioral alterations, including catalepsy, and the inhibition of stereotypic behavior induced by the D-2/D-3 DA receptor agonist quinpirole. Both of these behaviors returned to normal within 8 days after FNM treatment. D-2 AS treatment delayed the restoration of these FNM-induced behaviors. Thus, it reduced the rate of disappearance of the cataleptic behavior induced by FNM and significantly delayed the restoration of the stereotypic behavior induced by quinpirole. The changes induced by D-2 AS on D-2 receptor-mediated behaviors were reversed on cessation of D-2 AS treatment. A random oligomer given in the same amount and for the same length of time as that of the D-2 AS had no significant effects on either D-2 DA receptor synthesis or DA receptor-mediated behaviors. These studies demonstrate that in vivo administration of D-2 AS decreased the rate of recovery of D-2 DA receptors and inhibited the recovery of D-2 DA receptor-mediated behaviors after irreversible receptor inactivation and suggest that D-2 AS treatment inhibits the synthesis of a functional pool of D-2 DA receptors.
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Details
- Title
- D-2 DOPAMINE-RECEPTOR ANTISENSE OLIGODEOXYNUCLEOTIDE INHIBITS THE SYNTHESIS OF A FUNCTIONAL POOL OF D-2 DOPAMINE-RECEPTORS
- Creators
- Z H QinL W ZhouS P ZhangY M WangB Weiss
- Publication Details
- Molecular pharmacology, v 48(4), pp 730-737
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 8
- Grant note
- MH42148 / NIMH NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01MH042148 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:A1995TA56700022
- Scopus ID
- 2-s2.0-0028971293
- Other Identifier
- 991019184284704721
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- Web of Science research areas
- Pharmacology & Pharmacy