Biomaterial Database

CNS levels of mu opioid receptor (MOR-1) mRNA during chronic treatment with morphine or naltrexone. 1995

M Brodsky, and K Elliott, and A Hynansky, and C E Inturrisi

Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA.

The CNS levels of mu opioid receptor (MOR-1) mRNA were determined by solution hybridization in rats treated chronically with morphine or naltrexone. Morphine treatment (2 x 75 mg pellets were implanted SC on Day 1 and 2 more on Day 4) resulted in the development of tolerance to morphine's antinociceptive (analgesic) effect, as assessed by the hot plate procedure on treatment Day 7. Following the hot plate test, selected CNS regions were obtained by microdissection. The levels of MOR-1 mRNA in pg/microgram RNA ranged from 0.7 in sensorimotor cortex to 15.3 in medial thalamus. MOR-1 mRNA levels were not altered in the dorsal horn of spinal cord, nucleus raphe magnus, periaqueductal grey, hypothalamus, medial thalamus, or sensorimotor cortex. In a separate experiment, a 2 day exposure to naltrexone (2 x 30 mg pellets) had no effect on CNS levels of MOR-1 mRNA; however, after an 8 day exposure a decrease was detected in the nucleus raphe magnus (by 28%), hypothalamus (by 21%), and medial thalamus (by 27%). Chronic exposure to morphine or naltrexone did not result in alterations in the size of full-length MOR-1 mRNA from rat brain, or in the size of the region protected by the MOR-1 riboprobe (i.e., the entire coding region). Thus, the neuroadaptive processes associated with the development of analgesic tolerance to morphine do not involve concurrent changes in the steady-state levels of MOR-1 mRNA. Chronic treatment with naltrexone appears to produce a region-specific downregulation of MOR-1 mRNA levels, which may be secondary to the naltrexone-induced increase in mu receptor binding.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009020	Morphine	The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.	Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009271	Naltrexone	Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.	Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D009693	Nucleic Acid Hybridization	Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)	Genomic Hybridization,Acid Hybridization, Nucleic,Acid Hybridizations, Nucleic,Genomic Hybridizations,Hybridization, Genomic,Hybridization, Nucleic Acid,Hybridizations, Genomic,Hybridizations, Nucleic Acid,Nucleic Acid Hybridizations
D002490	Central Nervous System	The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.	Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004361	Drug Tolerance	Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.	Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012680	Sensitivity and Specificity	Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)	Specificity,Sensitivity,Specificity and Sensitivity