Escalation of i.v. cocaine intake in peri-adolescent vs. adult rats selectively bred for high (HiS) vs. low (LoS) saccharin intake

Abstract

Rationale: Adolescence marks a period of increased vulnerability to the development of substance use disorders. High sweet preference is a genetically mediated behavioral trait that also predicts vulnerability to substances of abuse. Previous research has shown that while adolescent rats selectively bred for high (HiS) saccharin intake acquire cocaine self-administration at the same rate as adult HiS rats, adolescent rats bred for low saccharin intake (LoS) acquire cocaine self-administration faster than adult LoS rats.

Objectives: This study was conducted to investigate the interaction of the addiction vulnerability factors of peri-adolescence and saccharin preference on cocaine intake using an animal model of escalation of cocaine consumption over 6-h/day sessions.

Methods: Peri-adolescent and adult HiS and LoS female rats self-administered i.v. cocaine (0.4 mg/kg/inf) during short-access (2-h/day) sessions for 2 days. Next, a long-access (6-h/day) period (LgA) commenced and lasted 16 days. Following LgA, session length was returned to 2-h/day for a second short access phase.

Results: LoS peri-adolescent rats escalated cocaine intake over the LgA period and consumed more drug than LoS adult rats; however, peri-adolescent and adult HiS rats consumed similar amounts of cocaine during this period. Additionally, adult HiS rats self-administered more cocaine than adult LoS rats during the LgA period, while there was no phenotypic difference between the rat lines during peri-adolescence for the LgA period. During the first short-access phase, peri-adolescent rats self-administered more cocaine than adult rats.

Conclusions: These results emphasize the importance of adolescent drug abuse prevention by illustrating that phenotypic protection from addiction may not be expressed until adulthood.

Fig. 1

Mean (±SEM) active lever responses (panel a) and infusions (panel b) during periods of short access before and after the long-access period (pre- and post-LgA). The @ indicates a main effect such that peri-adolescent rats made more responses than adults when data were collapsed across phenotype and short-access period (p<.05). The * indicates that peri-adolescent rats self-administered more cocaine infusions than adults during the pre-LgA period (p<.01)

Fig. 2

Mean (±SEM) active lever responses made during the period of long access (LgA) to cocaine. Responses were compared between HiS adults and peri-adolescents (panel a), HiS peri-adolescents and LoS peri-adolescents (panel b), LoS adolescents and adults (panel c), and HiS adults and LoS adults (panel d). The * indicates that LoS adolescents made significantly more responses during the last block of 4 days compared to LoS adults (p<.01)

Fig. 3

Mean (±SEM) cocaine infusions self-administered during the period of long access (LgA) to cocaine. Infusions were compared between HiS adults and adolescents (panel a), HiS adolescents and LoS adolescents (panel b), LoS adolescents and adults (panel c), and HiS adults and LoS adults (panel d). The * indicates that LoS adolescents self-administered more infusions during the second, third, and fourth block of 4 days than LoS adults (p<.01). The @ indicates a main effect of phenotype such that and that HiS adults earned more infusions than LoS adults during the LgA phase (p<.05). The # indicates that the LoS adolescent group self-administered more cocaine on the last block of 4 days compared to the first, indicating an escalation effect