Abstract
Previous studies have established that neuroleptic-induced catalepsy in mice is a highly heritable trait. The current study focuses on the detection of quantitative trait loci (QTL) for haloperidol-induced catalepsy in a BALB/cJ × LP/J F2 intercross. One thousand thirty-seven F2 animals were phenotyped and divided into four categories: very responsive (RR), responsive, nonresponsive, and very nonresponsive (NN). The RR and NN phenotypes comprised approximately 18% each of the total and differed in their haloperidol sensitivity by >10-fold. Sex differed significantly between the NN and RR groups (χ2 = 14.0;p < .0002); females comprised 58% of the RR individuals but only 38% of the NN individuals. The difference between the extreme phenotypes in the number of piebald animals was highly significant (χ2 = 30, p < .00001). Eight percent of the RR individuals were piebald compared with 30% of the NN individuals. A genome wide scan confirmed the presence of a QTL (peak LOD = 6.4) on chromosome 14 near the piebald (Ednrb) and 5-hydroxytryptamine2A(Htr2a) loci. Although the parental BALB/cJ and LP/J strains differed significantly in striatal 5-hydroxytryptamine2A receptor binding, no marked differences were detected between the phenotypic extremes. A second QTL was detected on chromosome 14 (peak LOD = 6.9), which was located more proximally and included the Chat locus. No QTLs were detected on chromosomes 1 and 9, thus differentiating this cross from previous results obtained for a C57BL/6J × DBA/2J intercross.
Footnotes
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Send reprint requests to: Dr. Robert Hitzemann, Department of Psychiatry, State University of New York at Stony Brook, Stony Brook, NY 11794-8101. E-mail: rhitzemann{at}mail.psychiatry.sunysb.edu
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↵1 This study was supported in part by Grant MH-51372 from the National Institute of Mental Health, National Institutes of Health; a grant from the Department of Veterans Affairs; and a grant from the National Alliance for Research on Schizophrenia and Depression (NARSAD).
- Abbreviations:
- PPI
- prepulse inhibition
- RI
- recombinant inbred
- QTL
- quantitative trait loci
- C
- BALB/cJ
- LP
- LP/J
- RR
- very responsive
- NN
- very nonresponsive
- R
- responsive
- N
- nonresponsive
- ASR
- acoustic startle response
- 5-HT
- 5-hydroxytryptamine
- PCR
- polymerase chain reaction
- 7-OH-DPAT
- 7-hydroxy-2-dipropylaminotetralin
- CPu
- caudate-putamen
- NAc
- nucleus accumbens
- B6
- C57BL/6J
- D2
- DBA/2J
- Received December 18, 1998.
- Accepted April 20, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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