Renewal of extinguished cocaine-seeking

• Published in: Neuroscience Vol. 151; no. 3; pp. 659 - 670
• Main Authors: Hamlin, A.S, Clemens, K.J, McNally, G.P
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.02.2008; Elsevier
• Subjects: Analysis of Variance; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Brain - cytology; Brain - drug effects; Brain - metabolism; Brain Mapping; Cell Count - methods; Cholera Toxin - metabolism; cocaine; Cocaine - administration & dosage; Cocaine-Related Disorders - etiology; Cocaine-Related Disorders - psychology; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Dopamine Uptake Inhibitors - administration & dosage; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Fundamental and applied biological sciences. Psychology; Intracellular Signaling Peptides and Proteins - metabolism; Male; Medical sciences; Neurology; Neurons - drug effects; Neurons - metabolism; Neuropeptides - metabolism; Neuropharmacology; orexin; Orexins; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-fos - metabolism; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; rat; Rats; Rats, Long-Evans; reinstatement; relapse; Self Administration; Time Factors; tracing; Vertebrates: nervous system and sense organs; VTA; 3V; cholera toxin, B subunit; cocaine; lateral hypothalamus; phosphate buffer; CTb; PeF; infralimbic region, prefrontal cortex; reinstatement; NHS; orexin; basolateral amygdala; DMH; PBS; tracing; rat; relapse; f; mt; IR; phosphate buffer saline; fornix; mammillothalamic tract; PBT-X; third ventricle; normal horse serum; phosphate buffer with Triton-X 10; perifornical hypothalamus; tyrosine hydroxylase; PB; ilPFC; TH; ventral tegmental area; BLA; immunoreactive/immunoreactivity; LH; dorsomedial hypothalamus; CNS stimulant; Rat; Psychotropic; Rodentia; Neuropeptide; Vertebrata; Mammalia; Animal; Drug of abuse; Cocaine; Orexin
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2007.11.018

Abstract 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.