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Across species, aging is associated with an increased ability to choose delayed over immediate gratification. These experiments used young and aged rats to test the role of the basolateral amygdala (BLA) in intertemporal decision making. An optogenetic approach was used to inactivate the BLA in young and aged rats at discrete time points during choices between levers that yielded a small, immediate vs. a large, delayed food reward. BLA inactivation just prior to decisions attenuated impulsive choice in both young and aged rats. In contrast, inactivation during receipt of the small, immediate reward increased impulsive choice in young rats but had no effect in aged rats. BLA inactivation during the delay or intertrial interval had no effect at either age. These data demonstrate that the BLA plays multiple, temporally distinct roles during intertemporal choice, and show that the contribution of BLA to choice behavior changes across the lifespan.

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.

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27Aging is associated with an increased ability to delay gratification. Moreover, even when matched for 28 performance, young and aged subjects recruit distinct brain circuitry to complete complex cognitive tasks. 29Experiments herein used an optogenetic approach to test whether altered recruitment of the basolateral 30 amygdala (BLA), a brain region implicated in valuation of reward-cost contingencies, contributes to age-31 dependent changes in intertemporal decision making. BLA inactivation while rats deliberated prior to choices 32 between options that yielded either small, immediate or large, delayed rewards rendered both young and aged 33 rats less impulsive. In contrast, BLA inactivation after choices were made (during evaluation of choice outcomes) 34 rendered young rats more impulsive but had no effect in aged rats. These data define multiple, temporally-35 discrete roles for BLA circuits in intertemporal decision making and implicate altered recruitment of BLA in the 36 elevated preference for delayed rewards that is characteristic of advanced age. 37 38 39 Keywords 40 aging, basolateral amygdala, optogenetics, decision making, delay discounting, impulsive choice 41 42 Abbreviations 43 basolateral amygdala (BLA); Fischer 344 x Brown Norway hybrid (FBN); intertrial interval (ITI) 44 45 Impact Statement 46 Basolateral amygdala (BLA) performs multiple, temporally-discrete functions during intertemporal decision 47 making. Differential engagement of BLA contributes to the enhanced ability to delay gratification that is 48 characteristic of advanced ages. 49 50