Dopamine D2 receptors bidirectionally regulate striatal enkephalin expression: Implications for cocaine reward.

Low dopamine D2 receptor (D2R) availability in the striatum can predispose for cocaine abuse; though how low striatal D2Rs facilitate cocaine reward is unclear. Overexpression of D2Rs in striatal neurons or activation of D2Rs by acute cocaine suppresses striatal Penk mRNA. Conversely, low D2Rs in D2-striatal neurons increases striatal Penk mRNA and enkephalin peptide tone, an endogenous mu-opioid agonist. In brain slices, met-enkephalin and inhibition of enkephalin catabolism suppresses intra-striatal GABA transmission. Pairing cocaine with intra-accumbens met-enkephalin during place conditioning facilitates acquisition of preference, while mu-opioid receptor antagonist blocks preference in wild-type mice. We propose that heightened striatal enkephalin potentiates cocaine reward by suppressing intra-striatal GABA to enhance striatal output. Surprisingly, a mu-opioid receptor antagonist does not block cocaine preference in mice with low striatal D2Rs, implicating other opioid receptors. The bidirectional regulation of enkephalin by D2R activity and cocaine offers insights into mechanisms underlying the vulnerability for cocaine abuse.

Cohort Analysis of Immigrant Rhetoric on Timely and Regular Access of Prenatal Care.

OBJECTIVE: To assess whether recent anti-immigration rhetoric is significantly associated with inadequate prenatal care. METHODS: This was a population-based cohort study (2011-2017). In their native language, patients were consented and queried regarding country of origin and time in the United States. Additional variables were collected or abstracted from the medical record, including documentation and timing of prenatal visits. Based on relevance and prevalence during the study period, publicly available Google search trends were mined for the terms "Make America Great Again," "Mexico Wall," and "Deportation" by geographic region. The time of first deviation from the mode Google search popularity value for each term was ascertained (mode inflection date). Perinatal data was averaged over 15 days moving windows, and the Adequacy of Prenatal Care Utilization Index was used to categorically define inadequate prenatal care by validated standards. RESULTS: Twenty-four thousand nine hundred thirty-three deliveries occurred during the study period. A mode inflection date was extrapolated from Google trend analytics and used to define the period before change in trends use pre (before rhetoric) and post (after rhetoric). Coincident to the rhetoric change, there was a significant increase in days until the first prenatal visit, fewer prenatal visits, and a decreased trend of mean hemoglobin nadir among U.S. non-native Hispanic women (P<.001). Immigrant status was an independent predictor of inadequate prenatal care as defined by the Adequacy of Prenatal Care Utilization Index standard, with increased adjusted odds among Hispanic women (adjusted odds ratio 1.581, 95% CI 1.407-1.777 [1.4-1.8]) coincident with anti-immigration rhetoric. CONCLUSION: Our findings are of likely significant public health importance and suggest that recent anti-immigrant rhetoric is associated with adequate, timely, and regular access to prenatal care among nearly 25,000 deliveries in Houston, Texas.