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Prenatal cocaine exposure and adolescent neural responses to appetitive and stressful stimuli.

ABSTRACT: Preclinical research has demonstrated the effects of prenatal cocaine exposure (PCE) on brain regions involved in emotional regulation, motivational control, and addiction vulnerability-eg, the ventral striatum (VS), anterior cingulate (ACC), and prefrontal cortex (PFC). However, little is known about the function of these regions in human adolescents with PCE. Twenty-two adolescents with PCE and 22 age-, gender-, and IQ-matched non-cocaine exposed (NCE) adolescents underwent functional magnetic resonance imaging (fMRI) during exposure to individually personalized neutral/relaxing, stressful, and favorite-food cues. fMRI data were compared using group-level two-tailed t-tests in the BioImage Suite. In comparison with NCE adolescents, PCE adolescents had reduced activity within cortical and subcortical brain regions, including the VS, ACC, and medial and dorslolateral PFC during exposure to favorite-food cues but did not differ in neural responses to stress cues. Subjective food craving was inversely related to dorsolateral PFC activation among PCE adolescents. Among PCE adolescents, subjective anxiety ratings correlated inversely with activations in the orbitofrontal cortex and brainstem during the stress condition and with ACC, dorsolateral PFC, and hippocampus activity during the neutral-relaxing condition. Thus adolescents with PCE display hypoactivation of brain regions involved in appetitive processing, with subjective intensities of craving and anxiety correlating inversely with extent of activation. These findings suggest possible mechanisms by which PCE might predispose to the development of addictions and related disorders, eg, substance-use disorders and binge-eating.

SUBMITTER: Yip SW

PROVIDER: S-EPMC4200493 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Prenatal cocaine exposure and adolescent neural responses to appetitive and stressful stimuli.

Yip Sarah W SW Potenza Elise B EB Balodis Iris M IM Lacadie Cheryl M CM Sinha Rajita R Mayes Linda C LC Potenza Marc N MN

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20140606 12

Preclinical research has demonstrated the effects of prenatal cocaine exposure (PCE) on brain regions involved in emotional regulation, motivational control, and addiction vulnerability-eg, the ventral striatum (VS), anterior cingulate (ACC), and prefrontal cortex (PFC). However, little is known about the function of these regions in human adolescents with PCE. Twenty-two adolescents with PCE and 22 age-, gender-, and IQ-matched non-cocaine exposed (NCE) adolescents underwent functional magnetic ...[more]

PMID: 24903650

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Project description:BACKGROUND:Prenatal cocaine exposure (PCE) is linked to addiction and obesity vulnerability. Neural responses to stressful and appetitive cues in adolescents with PCE versus those without have been differentially linked to substance-use initiation. However, no prior studies have assessed cue-reactivity responses among PCE adolescents using a connectivity-based approach. METHODS:Twenty-two PCE and 22 non-prenatally drug-exposed (NDE) age-, sex-, IQ- and BMI-matched adolescents participated in individualized guided imagery with appetitive (favorite-food), stressful and neutral-relaxing cue scripts during functional magnetic resonance imaging. Subjective favorite-food craving scores were collected before and after script exposure. A data-driven voxel-wise intrinsic connectivity distribution analysis was used to identify between-group differences and examine relationships with craving scores. RESULTS:A group-by-cue interaction effect identified a parietal lobe cluster where PCE versus NDE adolescents showed less connectivity during stressful and more connectivity during neutral-relaxing conditions. Follow-up seed-based connectivity analyses revealed that, among PCE adolescents, the parietal seed was positively connected to inferior parietal and sensory areas and negatively connected to corticolimbic during both stress and neutral-relaxing conditions. For NDE, greater parietal connectivity to parietal, cingulate and sensory areas and lesser parietal connectivity to medial prefrontal areas were found during stress compared to neutral-relaxing cueing. Craving scores inversely correlated with corticolimbic connectivity in PCE, but not NDE adolescents, during the favorite-food condition. CONCLUSIONS:Findings from this first data-driven intrinsic connectivity analysis of PCE influences on adolescent brain function indicate differences relating to PCE status and craving. These findings provide insight into the developmental impact of in utero drug exposure.

Project description:Prenatal cocaine exposure (PCE) can cause persistent neuropsychological and motor abnormalities in affected children, but the physiological consequences of PCE remain unclear. Conclusions drawn from clinical studies can sometimes be confounded by polysubstance abuse and nutritional deprivation. However, existing observations suggest that cocaine exposure in utero, as in adults, increases synaptic dopamine and promotes enduring dopamine-dependent plasticity at striatal synapses, altering behaviors and basal ganglia function.We used a combination of behavioral measures, electrophysiology, optical imaging, and biochemical and electrochemical recordings to examine corticostriatal activity in adolescent mice exposed to cocaine in utero.We show that PCE caused abnormal dopamine-dependent behaviors, including heightened excitation following stress and blunted locomotor augmentation after repeated treatment with amphetamine. These abnormal behaviors were consistent with abnormal ?-aminobutyric acid (GABA) interneuron function, which promoted a reversible depression in corticostriatal activity. PCE hyperpolarized and reduced tonic GABA currents in both fast-spiking and persistent low-threshold spiking type GABA interneurons to increase tonic inhibition at GABAB receptors on presynaptic corticostriatal terminals. Although D2 receptors paradoxically increased glutamate release following PCE, normal corticostriatal modulation by dopamine was reestablished with a GABAA receptor antagonist.The dynamic alterations at corticostriatal synapses that occur in response to PCE parallel the reported effects of repeated psychostimulants in mature animals, but differ in being specifically generated through GABAergic mechanisms. Our results indicate approaches that normalize GABA and D2 receptor-dependent synaptic plasticity may be useful for treating the behavioral effects of PCE and other developmental disorders that are generated through abnormal GABAergic signaling.

Dataset Information

Prenatal cocaine exposure and adolescent neural responses to appetitive and stressful stimuli.

Publications

Prenatal cocaine exposure and adolescent neural responses to appetitive and stressful stimuli.

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