Abstract
Prior studies have shown that drug-seeking behaviors increase, rather than dissipate, over weeks to months after withdrawal from drug self-administration. This phenomenon - termed incubation - suggests that drug-craving responses elicited by conditioned environmental or discrete cues may intensify over pronged abstinence. While most of this work is conducted in rats with intravenous drug self-administration models, there is less evidence for incubation in mice that have greater utility for molecular genetic analysis and perturbation. We tested whether incubation of cocaine-seeking behavior is evident in C57BL/6J mice following 3 weeks (5 days/week) of cocaine self-administration in 2 h self-administration sessions. We compared cocaine-seeking (drug-paired lever) responses 1, 7, or 28 days after withdrawal from cocaine self-administration, and over similar times following sucrose pellet self-administration. We found that the initial re-exposure to the self-administration test chambers elicited increased reward-seeking behavior in both sucrose and cocaine self-administering mice, with maximal responses found at 7 days compared to 1 or 28 days after self-administration with either reinforcer. However, following extinction training, reinstatement of cocaine seeking reinforced by response-contingent presentation of reward-associated cues (tone/light) was significantly higher after 28 days compared to 1 or 7 days following cocaine self-administration. In contrast, cue-induced reinstatement of sucrose-paired lever pressing did not increase over this time frame, demonstrating a drug-specific incubation effect not seen with a natural reward. Thus, C57BL/6J mice display incubation of cue-induced reinstatement of cocaine seeking similar to findings with rats, but only show a transient incubation of context-induced cocaine seeking.
Original language | English (US) |
---|---|
Pages (from-to) | 12-17 |
Number of pages | 6 |
Journal | Pharmacology Biochemistry and Behavior |
Volume | 159 |
DOIs | |
State | Published - Aug 2017 |
Keywords
- Cocaine
- Craving
- Cue-induced reinstatement
- Drug-seeking
- Extinction
- Incubation
- Mouse
- Self-administration
- Sucrose
- Sucrose-seeking
ASJC Scopus subject areas
- Biochemistry
- Toxicology
- Pharmacology
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience