Extinction of conditioned cues attenuates incubation of cocaine craving in adolescent and adult rats.
Relapse to drug use is often precipitated by exposure to drug associated cues that evoke craving. Cue-induced drug craving has been observed in both animals and humans to increase over the first few weeks of abstinence and remain high over extended periods, a phenomenon known as 'incubation of craving'. As adolescence represents a period of vulnerability to developing drug addiction, potentially due to persistent reactivity to drug associated cues, we first compared incubation of cocaine craving in adolescent and adult rats. Adolescent (P35) and adult (P70) rats were trained to lever press to obtain intravenous cocaine, with each drug delivery accompanied by a light cue that served as the conditioned stimulus (CS). Following acquisition of stable responding, rats were tested for cue-induced cocaine-seeking after either 1 or 30days of abstinence. Additional groups of rats were also tested after 30days of abstinence, however these rats were subjected to a cue extinction session 1week into the abstinence period. Rats were injected with aripiprazole, a dopamine 2 receptor (D2R)-like partial agonist, or vehicle, 30min prior to cue extinction. We found that adolescent and adult rats acquired and maintained a similar level of cocaine self-administration, and rats of both ages exhibited a higher level of cue-induced cocaine-seeking if they were tested after 30days of abstinence compared to 1day. Incubation of cocaine craving was significantly reduced to 1day levels in both adults and adolescents that received cue extinction training. Administration of aripiprazole prior to cue extinction did not further reduce cue-induced drug-seeking. These results indicate that cue extinction training during abstinence may effectively reduce cue-induced relapse at a time when cue-induced drug craving is usually high.
Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia.
Heather B
HB
Madsen
Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia.
Isabel C
IC
Zbukvic
Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia.
Sophia J
SJ
Luikinga
Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia.
Andrew J
AJ
Lawrence
Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: drjeehyunkim@gmail.com.
Jee Hyun
JH
Kim
D000818:Animals; D000068180:Aripiprazole / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant; D066249:Craving / Q000187:drug effects*; D003463:Cues; D058999:Drug-Seeking Behavior; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology; D012646:Self Administration
D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor; D000068180:Aripiprazole; D003042:Cocaine
Adolescent; Cocaine; Cues; Extinction; Incubation of craving; Self-administration