Enhanced acquisition of cocaine self-administration by increasing percentages of C57BL/6J genes in mice with a nonpreferring outbred background.
BACKGROUND
Individual differences in the propensity to acquire drug self-administration may have a substantial genetic basis.


OBJECTIVE
To study the genetic contribution to cocaine self-administration by comparing hybrids of cocaine preferring (C57BL/6J) and nonpreferring (ICR) mice.


METHODS
ICR and C57BL/6J parental strains were compared to hybrids with 75% ICR:25% C57BL/6J, 50% ICR:50% C57BL/6J, and 25% ICR:75% C57BL/6J genetic backgrounds for acquisition of sucrose pellet and intravenous cocaine self-administration in 1-h test sessions. Mice that acquired cocaine self-administration were subsequently tested in a between-session self-administration dose-response procedure.


RESULTS
Increasing presence of C57BL/6J genes increased the percentage of mice that acquired sucrose pellet self-administration in the first test session. In lever-trained mice, only 19% of ICR mice met acquisition criteria for cocaine self-administration after 15 sessions, whereas 76% of C57BL/6J mice met acquisition criteria, although both strains initially sampled a similar number of cocaine injections. Increasing the percentage of C57BL/6J genes in the nonpreferring ICR background to 50 and 75% led to increasing percentages of mice that met acquisition criteria to 31 and 52%, respectively. In mice that acquired self-administration, only mice with 75% C57BL/6J genes showed a typical inverted U-shaped self-administration dose-response curve, whereas the curve was flat across doses for mice with < or = 50 and 100% C57BL/6J genes.


CONCLUSIONS
The findings are consistent with a genetically based dose-dependent enhancement of cocaine reinforcement by C57BL/6J genes. These results suggest that heritable traits impart a substantial genetic load that facilitates the propensity for cocaine addiction among individuals in outbred populations.
Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Eduardo
E
Ruiz-Durántez
Stephanie K
SK
Hall
Cathy
C
Steffen
David W
DW
Self
D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000235:genetics*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006824:Hybridization, Genetic; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D012054:Reinforcement, Psychology; D012646:Self Administration
D000697:Central Nervous System Stimulants; D003042:Cocaine