Research: Developmental

Developmental Environmental Exposures as aÌý

Risk Factor for Substance Use Disorders

Adolescence represents a highly sensitive neurodevelopmental window during which the brain is uniquely susceptible to disruption by environmental factors, including drug exposure. Our research program focuses on developmental exposure to caffeine, the most widely consumed psychoactive drug in the world. ÌýEpidemiological data associate high caffeine intake in youth with an elevated risk for developing psychiatric disorders, including anxiety, as well as subsequent illicit substance use later in life. By modeling caffeine exposure in adolescent rats, our laboratory aims to uncover the exact mechanisms by which early-life exposure alters neurodevelopmental trajectories, creating lasting adult vulnerabilities to reward dysfunction, emotional dysregulation, and cognitive alterations.Ìý

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Neurodevelopmental Impacts & Active Investigations

Caffeine acts primarily by blocking adenosine receptors that normally serve to dampen dopamine and glutamate signaling and restrict neural excitability. Our foundational work demonstrated that caffeine consumption specifically during adolescence, but notably not during adulthood, produces long-lasting increases in adult anxiety-like behavior, dysregulation of stress responsivity, and an enhanced sensitivity to the reinforcing effects of cocaine (O'Neill et al., Neuropsychopharmacology, 2015; O'Neill et al., Psychoneuroendocrinology, 2016; Larson et al., J. Psychopharmacology, 2019). This developmental vulnerability is driven by a lasting recalibration of the adenosine, dopamine, and serotonin systems embedded within the brain's primary reward circuits. Collectively, these findings suggest that adolescent caffeine use fundamentally reshapes neural circuitry to increase the long-term risk for stimulant addiction.

To map the broader impact of early-life caffeine intake, we evaluate non-drug behaviors tightly linked to addiction vulnerability. Using a Pavlovian Conditioned Approach task, we discovered that adolescent caffeine biases animals toward a "sign-tracking" phenotype—a dopamine-dependent trait where an individual places excessive, compulsive value directly on reward-predictive cues. When investigating impulsivity traits, we find that developmental caffeine exposure paradoxically improved measures of both impulsive choice and impulsive action. Taken together, these studies reveal a highly complex behavioral profile: developmental caffeine simultaneously increases vulnerability to drug intake and reward cues while selectively improving specific domains of behavioral inhibitory control.Ìý

The divergent behavioral outcomes observed in our caffeine models provide the foundation for upcoming mechanistic studies. We are interested in mapping dopamine signaling dynamics and localized transcriptional adaptations within core brain reward circuits. We are also interested in investigating whether an individual's genetic background modulates these long-term neurodevelopmental effects. Given the profound phenotypic variation and distinct lines of resistance versus vulnerability discovered in our other studies, our upcoming efforts will systematically evaluate whether susceptibility or resilience to caffeine-induced reward and emotional dysregulation depends fundamentally on background genetics.