Renewal of extinguished cocaine-seeking.
Rats were trained to self-administer cocaine in a distinctive context (context A). They were then extinguished in a second context (context B) prior to test for cocaine-seeking in the original training context, context A (group ABA), context B (group ABB) or no test (group AB0). Group ABA showed renewal of extinguished cocaine-seeking associated with c-Fos induction in basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Groups ABA and ABB showed test-associated c-Fos induction in prelimbic prefrontal cortex, nucleus accumbens (core, shell, rostral pole), striatum, lateral amygdala, perifornical hypothalamus, and ventral tegmental area. Double immunofluorescence revealed that renewal-associated c-Fos was expressed in orexin-negative lateral hypothalamic neurons whereas test-associated c-Fos was expressed in orexin-positive perifornical hypothalamic neurons. Retrograde tracing from lateral hypothalamus with cholera toxin revealed only sparse dual-labeled neurons in basolateral amygdala and infralimbic prefrontal cortex, suggesting that these regions contribute to renewal of cocaine-seeking independently of their projections to lateral hypothalamus. Retrograde tracing from the ventral tegmental area suggested that hypothalamic contributions to cocaine-seeking are likewise independent of projections to the midbrain. These results suggest that renewal of cocaine-seeking depends critically on basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Whereas basolateral amygdala and lateral hypothalamus contributions may be common to renewal of extinguished cocaine-, alcohol-, and sucrose-seeking, infralimbic prefrontal cortex contributions appear unique to renewal of cocaine-seeking and may reflect the habitual nature of relapse to cocaine.
Hamlin
A S
AS
School of Psychology, The University of New South Wales, Sydney, New South Wales, 2052, Australia.
Clemens
K J
KJ
McNally
G P
GP
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001931:Brain Mapping; D002452:Cell Count / Q000379:methods; D002772:Cholera Toxin / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D002772:Cholera Toxin; D003042:Cocaine