Abstract
Cocaine abuse and dependence is a major public health problem that continues to challenge medication-based treatment. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on both serotonin and dopamine systems. In recent preclinical studies, acute buspirone treatment reduced cocaine self-administration at doses that did not also decrease food-reinforced behavior in rhesus monkeys (Bergman et al, 2012). The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of cocaine and food. Five adult rhesus monkeys (Macaca mulatta) were trained to self-administer cocaine and food during four 1-h daily sessions under a second-order schedule of reinforcement (FR2 [VR 16:S]). Buspirone (0.32 and 0.56 mg/kg/h) was administered intravenously through one lumen of a double-lumen catheter every 20 min for 23 h each day for 7–10 consecutive days. Each buspirone treatment period was followed by saline control treatment until drug- and food-maintained responding returned to baseline levels. Buspirone significantly reduced responding maintained by cocaine, and shifted the dose–effect curve downwards. Buspirone had minimal effects on food-maintained responding. In cocaine discrimination studies, buspirone (0.1–0.32 mg/kg, IM) did not antagonize the discriminative stimulus and rate-altering effects of cocaine in four of six monkeys. These findings indicate that buspirone selectively attenuates the reinforcing effects of cocaine in a nonhuman primate model of cocaine self-administration, and has variable effects on cocaine discrimination.
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Acknowledgements
This work was supported in part by grant number R01-DA002519 and R01-DA026892 (NK Mello, PI) from the National Institute on Drug Abuse, NIH. We thank Meredith Mahnke, Sherilyn Pattel, and Olga Smirnova for excellent technical assistance.
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Preliminary data were reported at the 2011 meeting of the American College of Neuropsychopharmacology.
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Mello, N., Fivel, P., Kohut, S. et al. Effects of Chronic Buspirone Treatment on Cocaine Self-Administration. Neuropsychopharmacol 38, 455–467 (2013). https://doi.org/10.1038/npp.2012.202
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DOI: https://doi.org/10.1038/npp.2012.202
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