Escalation of methamphetamine self-administration in adolescent and adult rats

Abstract

Background: Methamphetamine (METH) use has increased substantially in the last 10 years and poses a serious health concern, especially for young populations. Drug abuse primarily begins during adolescence, when uninhibited and excessive and drug intake is a common occurrence; thus, understanding the developmental patterns of addiction during this critical period is an essential step in its prevention. In the present study, the effect of age on the vulnerability to METH abuse was examined using a rat model of bingeing (i.e., escalation).

Methods: Adolescent and adult rats were compared during short (ShA, 2-h) and long-access (LgA, 6-h) to METH self-administration. On postnatal (PN) days 23 (adolescents) and 90 (adults), rats were implanted with i.v. catheters and trained to lever press for infusions of METH (0.05mg/kg) during 2-h sessions. Once the rats reached a steady rate of METH self-administration, they were divided into ShA or LgA groups and allowed to self-administer METH for 15 additional days.

Results: Results indicated that adolescent rats earned significantly more infusions than adults under the LgA condition, but the age groups did not differ during ShA. Adolescents, but not adults, also significantly increased (i.e., escalated) METH self-administration across the 15 days of testing under the LgA condition. Further analysis indicated excessive responding during infusions in the LgA METH-exposed adolescents compared to the other groups, suggesting elevated impulsivity or motivation for drug.

Conclusion: These results demonstrate that adolescents are more vulnerable to the escalation of METH than adults during LgA.

Fig. 1

Mean (±SEM) METH infusions earned by adolescent and adult male rats during fifteen ShA (2 h) or LgA (6 h) sessions. Adolescents earned significantly more METH infusions than adults under LgA sessions (*p < 0.01). However, there were no significant age differences in the ShA groups. Adolescents and adults under the LgA condition escalated METH intake during the last 3 days compared to the first 3 days of testing (^†p < 0.01).

Fig. 2

Mean (±SEM) nonreinforced active lever presses per 1 s of infusion time by adolescent and adult rats with ShA or LgA to i.v. METH. Adolescents (vs. adults) made significantly more nonreinforced responses during LgA sessions (*p < 0.05), but both groups responded equally under ShA conditions.