Long-term effects of exposure to methamphetamine in adolescent rats

Abstract

Background Flexible cognition is a set of processes mediated by the prefrontal cortex (PFC), an area of the brain that continues to develop during adolescence and into adulthood. Adult rodents exhibit impairments specific to reversal learning across various dosing regimens of methamphetamine (mAMPH). For adolescent rodents, ongoing PFC development can be assessed by discrimination reversal learning, a task dependent on frontostriatal integrity. The task may also index an increased vulnerability for mAMPH sampling in adulthood. Methods The purpose of the present study was to investigate the long-term effects of escalating, adolescent mAMPH exposure on reversal learning, a PFC-dependent task (Experiment 1) and the likelihood of later sampling of mAMPH in adulthood (Experiment 2). Results Unlike previous research in adult-treated rats, our results show more generalized learning impairments after adolescent mAMPH exposure to include both attenuated visual discrimination as well as reversal learning. Additionally, we found that rats pre-exposed to mAMPH during adolescence consumed significantly more drug in adulthood. Intake of mAMPH was positively correlated with this learning. Conculsion Taken together, these findings show that even modest exposure to mAMPH during adolescence may induce general learning impairments in adulthood, and an enduring sensitivity to the effects of mAMPH.

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

“…Surprisingly, mAMPH pretreated rats did not display the discrimination or reversal learning impairments we previously observed when animals were treated in later adolescence, beginning in PND 41 (Ye et al 2014). There is now evidence that there are differences in reward sensitivity and addiction vulnerability in early vs. late rat adolescence and that these effects are often sex dependent (Spear 2015).…”

“…There may also be a difference in the aversive properties of mAMPH depending on age of exposure: in one study, a 9 d difference in adolescence had a significant impact on drug response (Vorhees et al 2011). Importantly, Ye et al (2014) only treated and tested male rats, different than in the present study, where male rats were single-housed in the same room as female rats, and tested in chambers that, despite thorough cleaning, frequently had female rats present in them before male testing. Future experiments should systematically control for the effects of these conditions in learning.…”

“…The mAMPH group was treated until day 10 of injections and received SAL for the remaining 5 days of injections. This was done to ensure the treatment reached its maximum escalating dose (3 mg/kg) at day 10, to remain more consistent with the duration of treatment in our previous-published study (Ye et al 2014). However, mAMPH treatment in the present experiment was initiated 5 d earlier than in Ye et al (2014).…”

“…This was done to ensure the treatment reached its maximum escalating dose (3 mg/kg) at day 10, to remain more consistent with the duration of treatment in our previous-published study (Ye et al 2014). However, mAMPH treatment in the present experiment was initiated 5 d earlier than in Ye et al (2014). MPH doses were selected to remain consistent with the range of doses previously published, which are known to produce clinically relevant levels of drug in the plasma (Crawford et al 2011; Gerasimov et al 2000).…”

Effects of adolescent methamphetamine and nicotine exposure on behavioral performance and MAP-2 immunoreactivity in the nucleus accumbens of adolescent mice

“…Adolescent rats show enhanced rates of MA self-administration [17], enhanced MA-induced locomotor activation, and enhanced MA conditioned place preference (CPP) [18] compared to adult rats. MA exposure during adolescence induces long-term impairments in visual discrimination and reversal learning in rats [19]. In mice, MA exposure during early adolescence increases depression-like behavior and decreases vasopressin-immunoreactive neurons in the paraventricular nucleus of the hypothalamus [20].…”