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.
Ruiz-Durántez
Eduardo
E
Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Hall
Stephanie K
SK
Steffen
Cathy
C
Self
David W
DW
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