American clusters: using machine learning to understand health and health care disparities in the United States.

Health and health care access in the United States are plagued by high inequality. While machine learning (ML) is increasingly used in clinical settings to inform health care delivery decisions and predict health care utilization, using ML as a research tool to understand health care disparities in the United States and how these are connected to health outcomes, access to health care, and health system organization is less common. We utilized over 650 variables from 24 different databases aggregated by the Agency for Healthcare Research and Quality in their Social Determinants of Health (SDOH) database. We used k-means-a non-hierarchical ML clustering method-to cluster county-level data. Principal factor analysis created county-level index values for each SDOH domain and 2 health care domains: health care infrastructure and health care access. Logistic regression classification was used to identify the primary drivers of cluster classification. The most efficient cluster classification consists of 3 distinct clusters in the United States; the cluster having the highest life expectancy comprised only 10% of counties. The most efficient ML clusters do not identify the clusters with the widest health care disparities. ML clustering, using county-level data, shows that health care infrastructure and access are the primary drivers of cluster composition.

5-HT1B receptor agonist enhances breakpoint for cocaine on a progressive ratio (PR) schedule during maintenance of self-administration in female rats but reduces breakpoint for sucrose.

Background: Previous research showed that the 5-HT1B receptor agonist CP94253 enhanced cocaine reinforcement rate during maintenance of daily self-administration (SA), but inhibited reinforcement rate after 21 days of abstinence in male rats. Here we examined whether female rats show similar effects of CP94253 during maintenance as males across estrous cycle phases. Methods: Female rats trained on a fixed ratio 5 (FR5) cocaine reinforcement schedule were tested for the effects of CP94253 (5.6 mg/kg, s.c.) on cocaine reinforcement rate during each phase of the estrous cycle, with access to either low (0.075 and 0.1875) or high (0.375 and 0.75) cocaine doses available for 1 h sequentially in descending dose order. Other female and male rats trained on a progressive ratio (PR) schedule of cocaine or sucrose reinforcement were tested for CP94253 (0, 3.2, 5.6, and 10 mg/kg, s.c.) effects on reinforcement rate in 3-h sessions. CP94253 effects on responding during sucrose cue-reactivity were also examined post-abstinence. Results: Regardless of sex, CP94253 enhanced breakpoints on the PR schedule during maintenance of cocaine SA but attenuated breakpoints for sucrose reinforcement and decreased responding during sucrose cue-reactivity. FR results showed that CP94253 attenuated cocaine reinforcement rate during all estrous cycle phases except metestrus. Conclusions: Overall, we suggest that CP94253 increased incentive motivation for cocaine during maintenance of SA in female and male rats, yet decreased motivation for sucrose. We also suggest that 5-HT1BRs modulate motivation similarly across sexes except when females are in metestrus.

5-HT1B receptor agonist attenuates cocaine self-administration after protracted abstinence and relapse in rats.

BACKGROUND: The 5-HT1B receptor (5-HT1BR) agonist, CP94253, enhances cocaine intake during maintenance of self-administration (SA) but attenuates intake after 21 days of forced abstinence in male rats. AIMS: We examined whether CP94253 attenuates cocaine intake in female rats after a period of abstinence, and if these attenuating effects persist or revert to enhancing cocaine intake during resumption (i.e. relapse) of daily cocaine SA. METHODS: Male and female rats trained to lever press on a fixed ratio 5 schedule of cocaine reinforcement underwent ⩾21 days of forced abstinence. They were then tested for the effects of CP94253 (5.6 mg/kg, SC) or vehicle on cocaine SA. During the test session, rats had 1-h access to the training dose of cocaine (0.75 mg/kg, IV) followed by 1-h access to a lower cocaine dose (0.075 mg/kg, IV). Rats then resumed cocaine SA for 15 days to mimic relapse and were retested as done previously. Subsequently, rats underwent abstinence again (21-60 days) and were tested for CP94253 effects on locomotion and cue reactivity (i.e. responding for light/tone cues previously paired with cocaine infusions). RESULTS: Regardless of sex, CP94253 decreased cocaine intake after abstinence and during resumption of SA and decreased cue reactivity while having no effect on locomotion. CONCLUSIONS: CP94253 decreases cocaine intake and cocaine seeking in both males and females even after resumption of cocaine SA. These findings suggest that the inhibitory effects of CP94253 observed after abstinence are long-lasting, and therefore, 5-HT1BR agonists may have clinical efficacy as anti-relapse medications for cocaine use disorders.