Abstract
Marijuana is a prevalent illicit substance used by adolescents, and several studies have indicated that adolescent use can lead to long-term cognitive deficits including problems with attention and memory. However, preclinical animal studies that observe cognitive deficits after cannabinoid exposure during adolescence utilize experimenter administration of doses of cannabinoids that may exceed what an organism would choose to take, suggesting that contingency and dose are critical factors that need to be addressed in translational models of consequences of cannabinoid exposure. Indeed, we recently developed an adolescent cannabinoid self-administration paradigm in male rats, and found that prior adolescent self-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) resulted in improved working memory performance in adulthood. In addition, the doses self-administered were not as high as those that are found to produce memory deficits. However, given known sex differences in both drug self-administration and learning and memory processes, it is possible that cannabinoid self-administration could have different cognitive consequences in females. Therefore, we aimed to explore the effects of self-administered vs. experimenter-administered WIN in adolescent female rats on adult cognitive function. Female rats were trained to self-administer WIN daily throughout adolescence (postnatal day 34–59). A control group self-administered vehicle solution. The acute effects of adolescent WIN self-administration on memory were determined using a short-term spatial memory test 24 h after final SA session; and the long-term effects on cognitive performance were assessed during protracted abstinence in adulthood using a delayed-match-to-sample working memory task. In a separate experiment, females were given daily intraperitoneal (IP) injections of a low or high dose of WIN, corresponding to self-administered and typical experimenter-administered doses, respectively, or its vehicle during adolescence and working memory was assessed under drug-free conditions in adulthood. While self-administration of WIN in adolescence had no significant effects on short-term spatial memory or adult working memory, experimenter administration of WIN resulted in improved adult working memory performance that was more pronounced in the low dose group. Thus, low-dose adolescent WIN exposure, whether self-administered or experimenter-administered, results in either improvements or no change in adult working memory performance in female rats, similar to previous results found in males.
Highlights
Legal policy in the U.S regarding both medicinal and recreational use of marijuana has become increasingly relaxed over the last decade
Analysis of infusions earned during self-administration by rmANOVA with group (WIN vs. VEH) as the between subjects factor showed that infusion number increased over the course of self-administration, regardless of whether responding was for WIN or for vehicle solution (VEH; main effect of SA day, F(21,336) = 5.41, p < 0.001; no group × day interaction F(21,336) = 0.51, p = 0.97)
Females self-administered an average dose of 0.15–0.16 mg/kg WIN over the last 5 days of self-administration, similar to what we have previously observed in males, where the average daily dose was 0.22 mg/kg (Kirschmann et al, 2017)
Summary
Legal policy in the U.S regarding both medicinal and recreational use of marijuana has become increasingly relaxed over the last decade. Considering that the prevalence of marijuana use among adolescents is between 35 and 40 percent (Moss et al, 2014; Salas-Wright et al, 2016), it is crucial to understand the long-term effects of marijuana exposure during adolescence in order to properly inform any potential policy changes. Adolescence is a period of substantial neuronal development. The development of both the prefrontal cortex, a brain region required for higher-order cognitive processing, and the endocannabinoid system, responsible for modulating various physiological functions as well as the binding of exogenous cannabinoids, occur simultaneously (Spear, 2000; Schneider, 2008). Considering the concurrent changes in neuronal and cannabinoid system development, there is potential for marijuana use to cause cannabinoid-induced interference in the carefully orchestrated development of the adolescent brain, possibly resulting in long-term effects on cognition
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
