Cocaine-induced seizure thresholds

Quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains

Heather S. Hain, John Jr Crabbe, Susan E. Bergeson, John Belknap

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Seizures are a well known consequence of human cocaine abuse, and in rodent models, sensitivity to cocaine seizures has been shown to be strongly influenced by genotype. For example, several studies have reported significant differences between the C57BL/6 (B6) and DBA/2 (D2) inbred mouse strains in their sensitivity to cocaine-induced seizures. This prompted our use of the BXD recombinant inbred (RI) strain set and an F2 population derived from the B6 and D2 progenitor strains for further genetic analyses and for gene mapping efforts in this study. Cocaine was infused into the lateral tail vein, and the doses needed to induce a running bouncing clonic seizure and a tonic hindlimb extensor seizure were recorded for each mouse. In the BXD RI set, a genome-wide search was carried out for QTLs (quantitative trait loci), which are sites on a chromosome containing genes that influence seizure susceptibility. An F2 population (B6D2F2, n = 408) was subsequently used as a second, confirmation step. Based on both RI and F2 results three QTLs emerged as significant (P <.00005): one for clonic seizures on chromosome 9 (distal), and two for tonic seizures on chromosomes 14 (proximal to mid) and 15 (distal). Two additional QTLs emerged as suggestive (P <.0015), both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific with much larger effects on the phenotype seen in females than in males.

Original languageEnglish (US)
Pages (from-to)180-187
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume293
Issue number1
StatePublished - Apr 2000

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Inbred DBA Mouse
Quantitative Trait Loci
Cocaine
Seizures
Population
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 14
Cocaine-Related Disorders
Inbred Strains Mice
Chromosome Mapping
Hindlimb
Running
Tail
Veins
Rodentia
Chromosomes
Genotype
Genome
Phenotype

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cocaine-induced seizure thresholds : Quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains. / Hain, Heather S.; Crabbe, John Jr; Bergeson, Susan E.; Belknap, John.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 293, No. 1, 04.2000, p. 180-187.

Research output: Contribution to journalArticle

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