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Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system.
- Source :
-
Neuroscience [Neuroscience] 2016 Jun 02; Vol. 324, pp. 50-61. Date of Electronic Publication: 2016 Feb 27. - Publication Year :
- 2016
-
Abstract
- Intensification of craving elicited by drug-associated cues during abstinence occurs over time in human cocaine users while elevation of cue reactivity ("incubation") is observed in rats exposed to extended forced abstinence from cocaine self-administration. Incubation in rodents has been linked to time-dependent neuronal plasticity in the medial prefrontal cortex (mPFC). We tested the hypothesis that incubation of cue reactivity during abstinence from cocaine self-administration is accompanied by lower potency and/or efficacy of the selective serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonist WAY163909 to suppress cue reactivity and a shift in the subcellular localization profile of the mPFC 5-HT2CR protein. We observed incubation of cue reactivity (measured as lever presses reinforced by the discrete cue complex) between Day 1 and Day 30 of forced abstinence from cocaine relative to sucrose self-administration. Pharmacological and biochemical analyses revealed that the potency of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity, the expression of synaptosomal 5-HT2CR protein in the mPFC, and the membrane to cytoplasmic expression of the 5-HT2CR in mPFC were lower on Day 30 vs. Day 1 of forced abstinence from cocaine self-administration. Incubation of cue reactivity assessed during forced abstinence from sucrose self-administration did not associate with 5-HT2CR protein expression in the mPFC. Collectively, these outcomes are the first indication that neuroadaptations in the 5-HT2CR system may contribute to incubation of cocaine cue reactivity.<br /> (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Attention drug effects
Attention physiology
Azepines pharmacology
Cell Membrane drug effects
Cell Membrane metabolism
Cocaine-Related Disorders metabolism
Cohort Studies
Conditioning, Operant drug effects
Conditioning, Operant physiology
Cues
Cytoplasm drug effects
Cytoplasm metabolism
Dietary Sucrose administration & dosage
Drug-Seeking Behavior drug effects
Indoles pharmacology
Male
Prefrontal Cortex metabolism
RNA, Messenger metabolism
Rats, Sprague-Dawley
Self Administration
Serotonin 5-HT2 Receptor Agonists pharmacology
Substance Withdrawal Syndrome drug therapy
Time Factors
Cocaine administration & dosage
Dopamine Uptake Inhibitors administration & dosage
Drug-Seeking Behavior physiology
Prefrontal Cortex drug effects
Receptor, Serotonin, 5-HT2C metabolism
Substance Withdrawal Syndrome metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 324
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 26926963
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2016.02.052