Repeated 7-Day Treatment with the 5-HT2C Agonist Lorcaserin or the 5-HT2A Antagonist Pimavanserin Alone or in Combination Fails to Reduce ... View Full Text


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Article Info

DATE

2016-11-18

AUTHORS

Matthew L Banks, S Stevens Negus

ABSTRACT

Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT2C agonist lorcaserin (0.1–1.0 mg/kg per day, intramuscular; 0.032–0.1 mg/kg/h, intravenous) or the 5-HT2A inverse agonist/antagonist pimavanserin (0.32–10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent ‘choice’ schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT2C receptor activation nor 5-HT2A receptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT2C agonists and 5-HT2A inverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies. More... »

PAGES

1082-1092

References to SciGraph publications

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  • 2002-04-19. 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") and its stereoisomers as reinforcers in rhesus monkeys: serotonergic involvement in PSYCHOPHARMACOLOGY
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  • 2004-04-27. Effects of the kappa opioid agonist U50,488 and the kappa opioid antagonist nor-binaltorphimine on choice between cocaine and food in rhesus monkeys in PSYCHOPHARMACOLOGY
  • 2014-10-21. Effects of buspirone and the dopamine D3 receptor compound PG619 on cocaine and methamphetamine self-administration in rhesus monkeys using a food-drug choice paradigm in PSYCHOPHARMACOLOGY
  • 2014-07-17. Effects of quetiapine treatment on cocaine self-administration and behavioral indices of sleep in adult rhesus monkeys in PSYCHOPHARMACOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/npp.2016.259

    DOI

    http://dx.doi.org/10.1038/npp.2016.259

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27857126


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