title: A role for the insular cortex in long-term memory for context-evoked drug craving in rats.
abstract: Drug craving critically depends on the function of the interoceptive insular cortex, and may be triggered by contextual cues. However, the role of the insula in the long-term memory linking context with drug craving remains unknown. Such a memory trace probably resides in some neocortical region, much like other declarative memories. Studies in humans and rats suggest that the insula may include such a region. Rats chronically implanted with bilateral injection cannulae into the high-order rostral agranular insular cortex (RAIC) or the primary interoceptive posterior insula (pIC) were conditioned to prefer the initially aversive compartment of a 2-compartment place preference apparatus by repeatedly pairing it to amphetamine. We found a reversible but long-lasting loss (ca. 24 days) of amphetamine-conditioned place preference (CPP) and a decreased expression in the insula of zif268, a crucial protein in memory reconsolidation, when anisomycin (ANI) was microinjected into the RAIC immediately after the reactivation of the conditioned amphetamine/context memory. ANI infusion into the RAIC without reactivation did not change CPP, whereas ANI infusion into pIC plus caused a 15 days loss of CPP. We also found a 24 days loss of CPP when we reversibly inactivated pIC during extinction trials. We interpret these findings as evidence that the insular cortex, including the RAIC, is involved in a context/drug effect association. These results add a drug-related memory function to the insular cortex to the previously found role of the pIC in the perception of craving or malaise.
authors.affiliation: Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marco
authors.initials: M
authors.lastname: Contreras
authors.forename: Pablo
authors.initials: P
authors.lastname: Billeke
authors.forename: Sergio
authors.initials: S
authors.lastname: Vicencio
authors.forename: Carlos
authors.initials: C
authors.lastname: Madrid
authors.forename: Guetón
authors.initials: G
authors.lastname: Perdomo
authors.forename: Marcela
authors.initials: M
authors.lastname: González
authors.forename: Fernando
authors.initials: F
authors.lastname: Torrealba
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D016739:Behavior, Addictive / Q000503:physiopathology / Q000523:psychology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000841:Anisomycin; D000661:Amphetamine