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Background: Cannabis (marijuana) is the most widely used illicit drug in the USA, and consumption among adolescents is rising. Some animal studies show that adolescent exposure to delta 9-tetrahydrocannabinol or synthetic cannabinoid receptor 1 agonists causes alterations in affect and cognition that can persist into adulthood. It is less clear, however, whether similar alterations result from exposure to cannabis via smoke inhalation, which remains the most frequent route of administration in humans. Aims: To begin to address these questions, a rat model was used to determine how cannabis smoke exposure during adolescence affects behavioral and cognitive outcomes in adulthood. Methods: Adolescent male Long-Evans rats were assigned to clean air, placebo smoke, or cannabis smoke groups. Clean air or smoke exposure sessions were conducted daily during adolescence (from P29–P49 days of age ) for a total of 21 days, and behavioral testing began on P70. Results: Compared to clean air and placebo smoke conditions, cannabis smoke significantly attenuated the normal developmental increase in body weight, but had no effects on several measures of either affect/motivation (open field activity, elevated plus maze, instrumental responding under a progressive ratio schedule of reinforcement) or cognition (set shifting, reversal learning, intertemporal choice). Surprisingly, however, in comparison to clean air controls rats exposed to either cannabis or placebo smoke in adolescence exhibited enhanced performance on a delayed response working memory task. Conclusions: These findings are consistent with a growing body of evidence for limited long-term adverse cognitive and affective consequences of adolescent exposure to relatively low levels of cannabinoids.

Numerous preclinical studies show that acute cannabinoid administration impairs cognitive performance. Almost all of this research has employed cannabinoid injections, however, whereas smoking is the preferred route of cannabis administration in humans. The goal of these experiments was to systematically determine how acute exposure to cannabis smoke affects working memory performance in a rat model. Adult male (n = 15) and female (n = 16) Long-Evans rats were trained in a food-motivated delayed response working memory task. Prior to test sessions, rats were exposed to smoke generated by burning different numbers of cannabis or placebo cigarettes, using a within-subjects design. Exposure to cannabis smoke had no effect on male rats’ performance, but surprisingly, enhanced working memory accuracy in females, which tended to perform less accurately than males under baseline conditions. In addition, cannabis smoke enhanced working memory accuracy in a subgroup of male rats that performed comparably to the worst-performing females. Exposure to placebo smoke had no effect on performance, suggesting that the cannabinoid content of cannabis smoke was critical for its effects on working memory. Follow-up experiments showed that acute administration of either Δ9-tetrahydrocannabinol (0.0, 0.3, 1.0, 3.0 mg/kg) or the cannabinoid receptor type 1 antagonist rimonabant (0.0, 0.2, 0.6, 2.0 mg/kg) impaired working memory performance. These results indicate that differences in the route, timing, or dose of cannabinoid administration can yield distinct cognitive outcomes, and highlight the need for further investigation of this topic.

The ability to decide advantageously among options that vary in both their risks and rewards is critical for survival and well-being. Previous work shows that some forms of risky decision making are robustly modulated by monoamine signaling, but it is less clear how monoamine signaling modulates decision making under risk of explicit punishment. The goal of these experiments was to determine how this form of decision making is modulated by dopamine, serotonin, and norepinephrine signaling, using a task in which rats choose between small, “safe” food rewards and large food rewards associated with variable risks of punishment. Preference for the large, risky reward (risk taking) was reduced by administration of a D2/3 dopamine receptor agonist (bromocriptine) and a selective D2 agonist (sumanirole). The selective D3 agonist PD128907 appeared to attenuate reward discrimination abilities, but did not affect risk taking per se. In contrast, drugs targeting serotonergic and noradrenergic signaling had few if any effects on choice behavior. These data suggest that in contrast to other forms of risky decision making, decision making under risk of punishment is selectively modulated by dopamine signaling, predominantly through D2 receptors.