Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats.
BACKGROUND
Drug-paired stimuli elicit drug craving and relapse in addicts and drug-seeking behavior in rats. The functional integrity of the basolateral amygdala (BLA) is necessary for reinstatement of cocaine-seeking behavior elicited by cocaine-conditioned stimuli, but not by cocaine itself. It is unclear, however, whether the BLA plays a similar role in reinstatement of heroin-seeking behavior.


OBJECTIVE
To this end, we examined the effects of tetrodotoxin (TTX)-induced inactivation of the BLA on conditioned and heroin-primed reinstatement of extinguished heroin-seeking behavior.


METHODS
Rats were trained to press a lever for IV infusions of heroin (maintenance dose of 25 microg/infusion) paired with presentations of a light-tone stimulus complex during daily 3-h sessions. Responding was then allowed to extinguish prior to reinstatement testing. Reinstatement of extinguished heroin-seeking behavior (i.e. lever pressing in the absence of heroin reinforcement) was measured in the presence of response-contingent presentation of the heroin-paired stimulus complex alone and then following TTX (5 ng/0.5 microl per side) or vehicle infused into the BLA. In a separate group of rats, reinstatement was measured after saline injection (SC) and then following heroin priming (0.25 mg/kg, SC) with TTX or vehicle infused into the BLA.


RESULTS
Both response contingent presentation of the stimulus complex and heroin priming significantly reinstated extinguished heroin-seeking behavior, and BLA inactivation abolished the ability of the heroin-paired stimuli and of heroin priming to reinstate responding.


CONCLUSIONS
These findings suggests that the BLA is a critical component of the neural circuitry that mediates conditioned and heroin-induced reinstatement of heroin-seeking behavior. Furthermore, different neural substrates may mediate drug-primed relapse to cocaine versus heroin-seeking behavior.
Fuchs
Rita A
RA
Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
See
Ronald E
RE
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology* / Q000523:psychology; D002404:Catheterization; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012646:Self Administration; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology
D000779:Anesthetics, Local; D009294:Narcotics; D013779:Tetrodotoxin; D003932:Heroin