Context-driven cocaine-seeking in abstinent rats increases activity-regulated gene expression in the basolateral amygdala and dorsal hippocampus differentially following short and long periods of abstinence

• Published in: Neuroscience Vol. 170; no. 2; pp. 570 - 579
• Main Authors: Hearing, M.C, Schochet, T.L, See, R.E, McGinty, J.F
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 13.10.2010; Elsevier
• Subjects: addiction; Amygdala; Amygdala - metabolism; Animals; arc; Behavior, Addictive - genetics; Behavior, Addictive - metabolism; Biological and medical sciences; cocaine; Cocaine - administration & dosage; Conditioning, Operant; Cues; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Early Growth Response Protein 1 - genetics; Early Growth Response Protein 1 - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression; Hippocampus - metabolism; in situ hybridization; Male; Medical sciences; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Self Administration; Time Factors; Vertebrates: nervous system and sense organs; zif268; DG; cocaine no lever; cocaine; saline alternate environment; SA; arc; analysis of variance; cocaine alternate environment; ANOVA; zif268; SL; basolateral amygdala; ID; SN; CA; activity-regulated cytoskeleton gene; cocaine lever available; saline lever available; addiction; saline no lever available; CL; CN; standard error mean; dentate gyrus; integrated density; dorsal hippocampus; self-administration; BLA; dHPC; SEM; in situ hybridization; Molecular hybridization; CNS stimulant; Amygdala; Rat; Psychotropic; Rodentia; Central nervous system; Basal ganglion; Self administration; Gene expression; Encephalon; Vertebrata; Mammalia; Animal; EGR1 transcription factor; Drug of abuse; Cocaine; Hippocampus
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.07.027

Abstract In this study, the expression patterns of zif268 and activity-regulated cytoskeleton-associated gene ( arc ) were investigated in the basolateral amygdala (BLA) and dorsal hippocampal (dHPC) subregions during context-induced drug-seeking following 22 h or 15 d abstinence from cocaine self-administration. Arc and zif/268 mRNA in BLA and dHPC increased after re-exposure to the cocaine-paired chamber at both timepoints; however, only the BLA increases (with one exception-see below) were differentially affected by the presence or absence of the cocaine-paired lever in the chamber. Following 22 h of abstinence, arc mRNA was significantly increased in the BLA of cocaine-treated rats re-exposed to the chamber only with levers extended, whereas following 15 d of abstinence, arc mRNA in the BLA was increased in cocaine-treated rats returned to the chamber with or without levers extended. In contrast, zif268 mRNA in the BLA was greater in cocaine-treated rats returned to the chamber with levers extended vs. levers retracted only after 15 d of abstinence. In the dentate gyrus (DG) following 22 h of abstinence, zif268 mRNA was greater in rats returned to the chamber where levers were absent regardless of drug treatment whereas arc mRNA was increased in CA1 (cell bodies and dendrites) and CA3 only in cocaine-treated groups. Following 15 d of abstinence, arc mRNA was significantly greater in CA1 and CA3 of both cocaine-treated groups returned to the chamber than in those placed into a familiar, non-salient alternate environment; however, only in CA1 cell bodies the cocaine context-induced increases significantly greater than in yoked-saline controls. In contrast, zif/268 mRNA in all dHPC regions was significantly greater in both cocaine-treated groups returned to the cocaine context than in the cocaine-treated group returned to an alternative environment or saline-treated groups. These data suggest that the temporal dynamics of arc and zif268 gene expression in the BLA and dHPC encode different key elements of drug context-induced cocaine-seeking.