Abstract
Genetic correlations were found between high-affinity neurotensin receptor (NTRH) densities and NT-immunoreactivity (NT-ir) levels in specific brain regions and sensitivity to hypnotic and hypothermic effects of ethanol in LSXSS recombinant inbred strains of mice. Simple sequence length polymorphisms were used to identify quantitative trait loci (QTL) influencing hypnotic and hypothermic sensitivity to ethanol, NTRH and low-affinity neurotensin receptor densities and NT-ir levels in LSXSS recombinant inbred strains. Common QTL for NTRH receptor densities, NT-ir levels and these ethanol actions were identified. One of the QTL (chromosome 2, 80 cM) for NTRH density and hypnotic sensitivity is linked to the NTRH gene, Ntsr. Also, QTL for NTRH density were found in common with confirmed QTL for hypnotic sensitivity on chromosomes 1 (43 cM), 11 (57 cM) and 15 (56 cM) and with an unconfirmed QTL on chromosome 3 (19 cM). Two common QTL for NT-ir levels, but not NTRH or low-affinity neurotensin receptor receptors, and ethanol-induced hypothermia were observed on chromosomes 4 (43 cM) and 6 (41 cM). Two common QTL for NT-ir levels and sleep time were identified on chromosomes 3 (19 cM) and 9 (55 cM). Common QTL indicate that genes regulating NT receptor and/or NT-ir expression may be the same as those regulating sensitivity to ethanol.
Footnotes
-
Send reprint requests to: Dr. V. Gene Erwin, School of Pharmacy, UCHSC, Box 238, 4200 East 9th Ave., Denver, CO 80262.
-
↵1 This work was supported, in part, by USPHS Grants AA 03527, AA 08940 and AA 07330.
-
↵2 Current address: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309.
- Abbreviations:
- NT
- neurotensin
- NTRH and NTRL
- high- and low-affinity neurotensin receptor, respectively
- NT-ir
- neurotensin-immunoreactivity
- QTL
- quantitative trait loci
- RI
- recombinant inbred
- cM
- centiMorgan
- VMB
- ventral midbrain
- STR
- striatum (includes nucleus accumbens, NA, and caudate putamen)
- HYP
- hypothalamus
- ST
- sleep time (duration of loss of righting response after 4.2 g/kg ethanol) and BECRR, blood ethanol concentration at regaining righting response
- FC
- frontal cortex
- SSLP
- simple sequence length polymorphism
- Received February 19, 1996.
- Accepted October 21, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
