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GABA_B receptors in prelimbic cortex and basolateral amygdala differentially influence intertemporal decision making and decline with age.

ABSTRACT: The ability to decide adaptively between immediate vs. delayed gratification (intertemporal choice) is critical for well-being and is associated with a range of factors that influence quality of life. In contrast to young adults, many older adults show enhanced preference for delayed gratification; however, the neural mechanisms underlying this age difference in intertemporal choice are largely un-studied. Changes in signaling through GABA_B receptors (GABA_BRs) mediate several age-associated differences in cognitive processes linked to intertemporal choice. The current study used a rat model to determine how GABA_BRs in two brain regions known to regulate intertemporal choice (prelimbic cortex; PrL and basolateral amygdala; BLA) contribute to age differences in this form of decision making in male rats. As in humans, aged rats showed enhanced preference for large, delayed over small, immediate rewards during performance in an intertemporal choice task in operant test chambers. Activation of PrL GABA_BRs via microinfusion of the agonist baclofen increased choice of large, delayed rewards in young adult rats but did not influence choice in aged rats. Conversely, infusion of baclofen into the BLA strongly reduced choice of large, delayed rewards in both young adult and aged rats. Aged rats further showed a significant reduction in expression of GABA_BR1 subunit isoforms in the prefrontal cortex, a discovery that is consonant with the null effect of intra-PrL baclofen on intertemporal choice in aged rats. In contrast, expression of GABA_BR subunits was generally conserved with age in the BLA. Jointly, these findings elucidate a role for GABA_BRs in intertemporal choice and identify fundamental features of brain maturation and aging that mediate an improved ability to delay gratification.

SUBMITTER: Hernandez CM

PROVIDER: S-EPMC9297337 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Adolescent drug misuse represents a major risk factor for long-term drug use disorders. However, wide individual differences in responses to first-line behavioral therapies targeting adolescent drug misuse limit critical early intervention. Identifying the neural signatures of those adolescents most likely to respond to an intervention would potentially guide personalized strategies for reducing drug misuse. Prior to a 14-week evidence-based intervention involving combinations of contingency management, motivational enhancement, and cognitive behavioral therapy, thirty adolescent alcohol and/or cannabis users underwent fMRI while performing a reward delay discounting (DD) task tapping an addiction-related cognition. Intervention responses were longitudinally characterized by both urinalysis and self-report measures of the percentage of days used during treatment and in post-treatment follow-up. Group independent component analysis (ICA) of task fMRI data identified neural processing networks related to DD task performance. Separate measures of wholesale recruitment during immediate reward choices and within-network functional connectivity among selective networks significantly predicted intervention-related changes in drug misuse frequency. Specifically, heightened pre-intervention engagement of a temporal lobe "reward motivation" network for impulsive choices on the DD task predicted poorer intervention outcomes, while modes of functional connectivity within the reward motivation network, a prospection network, and a posterior insula network demonstrated robust associations with intervention outcomes. Finally, the pre-intervention functional organization of the prospection network also predicted post-intervention drug use behaviors for up to 6 months of follow-up. Multiple functional variations in the neural processing networks supporting preference for immediate and future rewards signal individual differences in readiness to benefit from an effective behavioral therapy for reducing adolescent drug misuse. The implications for efforts to boost therapy responses are discussed.

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GABA_B receptors in prelimbic cortex and basolateral amygdala differentially influence intertemporal decision making and decline with age.

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Dataset Information

GABAB receptors in prelimbic cortex and basolateral amygdala differentially influence intertemporal decision making and decline with age.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

GABA_B receptors in prelimbic cortex and basolateral amygdala differentially influence intertemporal decision making and decline with age.