Abstract
The lateral preoptic–rostral lateral hypothalamic continuum (LPH) receives projections from the nucleus accumbens and is believed to be one route by which nucleus accumbens signaling affects motivated behaviors. While accumbens firing patterns are known to be modulated by fluctuating levels of cocaine, studies of the LPH’s drug-related firing are absent from the literature. The present study sought to electrophysiologically test whether drug-related tonic and slow-phasic patterns exist in the firing of LPH neurons during a free-access cocaine self-administration task. Results demonstrated that a majority of neurons in the LPH exhibited changes in both tonic and slow-phasic firing rates during fluctuating drug levels. During the maintenance phase of self-administration, 69.6 % of neurons exhibited at least a twofold change in tonic firing rate when compared to their pre-drug firing rates. Moreover, 54.4 % of LPH neurons demonstrated slow-phasic patterns, specifically “progressive reversal” patterns, which have been shown to be related to pharmacological changes across the inter-infusion interval. Firing rate was correlated with calculated drug level in 58.7 % of recorded cells. Typically, a negative correlation between drug level and firing rate was observed, with a majority of neurons showing decreases in firing during cocaine self-administration. A small percentage of LPH neurons also exhibited correlations between locomotor behavior and firing rate; however, correlations with drug level in these same neurons were always stronger. Thus, the weak relationships between LPH firing and locomotor behaviors during cocaine self-administration do not account for the observed changes in firing. Overall, these findings suggest that a proportion of LPH neurons are sensitive to fluctuations in cocaine concentration and may contribute to neural activity that controls drug taking.
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Acknowledgments
The authors thank Dr. D.S. Zahm for his advice during the preparation of the manuscript. We also thank Jackie Thomas, Joshua Stamos, and Sisi Ma for technical assistance. This study was supported by the National Institute on Drug Abuse Grants DA06886 (MOW) DA 029873 (MOW) and DA032270 (DJB). The authors have no financial interests to disclose. The funders had no role in study design, data collection, data analysis, decision to publish, or manuscript preparation. DJB, BMS, KCC, DHR, JK, and ATF collected and organized the data for analysis. DJB, BMS, APP, and OAK conducted analyses of the data. DJB, BMS, and MOW were responsible for writing the manuscript. MOW was responsible for critical commentary and project oversight.
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Barker, D.J., Striano, B.M., Coffey, K.C. et al. Sensitivity to self-administered cocaine within the lateral preoptic–rostral lateral hypothalamic continuum. Brain Struct Funct 220, 1841–1854 (2015). https://doi.org/10.1007/s00429-014-0736-6
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DOI: https://doi.org/10.1007/s00429-014-0736-6