Role of dopamine D(1)-family receptors in dorsolateral striatum in context-induced reinstatement of heroin seeking in rats.
BACKGROUND
In humans, exposure to environmental contexts previously associated with heroin intake can provoke relapse to drug use. In rats, exposure to heroin-associated contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. This effect is attenuated by blockade of D(1)-family receptors in lateral or medial accumbens shell, but not accumbens core.


OBJECTIVE
In this study, we further characterized the role of striatal D(1)-family receptors in context-induced reinstatement by assessing the effect of dorsolateral or dorsomedial injections of the D(1)-family receptor antagonist SCH 23390 on this reinstatement.


METHODS
Rats were trained to self-administer heroin (0.05-0.10 mg/kg per infusion) for 12 days; drug infusions were paired with a discrete tone-light cue. Subsequently, heroin-reinforced lever pressing was extinguished in the presence of the discrete cue in a nondrug context. During reinstatement tests under extinction conditions, the D(1)-family receptor antagonist SCH 23390 (0.3-1.0 microg per side) was injected into the dorsolateral or dorsomedial striatum prior to exposure to heroin self-administration context or the nondrug (extinction) context. We then used a disconnection procedure to examine whether D(1)-family receptors in the dorsolateral striatum and lateral accumbens shell jointly or independently support context-induced reinstatement.


RESULTS
Dorsolateral but not dorsomedial SCH 23390 injections attenuated context-induced reinstatement of heroin seeking. SCH 23390 injections into the dorsolateral striatum of one hemisphere and lateral accumbens shell of the other hemisphere were ineffective.


CONCLUSIONS
Results indicate that dorsolateral striatum D(1)-family dopamine receptors are critical for context-induced reinstatement of heroin seeking. Results also suggest that D(1)-receptor-mediated dopamine transmission in the dorsolateral striatum and lateral accumbens shell independently support this reinstatement.
Bossert
Jennifer M
JM
Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, 251 Bayview Boulevard, Baltimore, MD 21224, USA. jbossert@intra.nida.nih.gov
Wihbey
Kristina A
KA
Pickens
Charles L
CL
Nair
Sunila G
SG
Shaham
Yavin
Y
D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D003932:Heroin / Q000008:administration & dosage* / Q000494:pharmacology; D006556:Heroin Dependence / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012055:Reinforcement Schedule; D012201:Reward; D055502:Secondary Prevention; D012646:Self Administration
D001552:Benzazepines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D003932:Heroin