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 amphetamineconditioned 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.

The auditory efferent system comprises descending projections from the cerebral cortex to subcortical nuclei, reaching the cochlear receptor through olivocochlear fibres. One of the functions attributed to this corticofugal system is to suppress irrelevant sounds during selective attention to visual stimuli. Medial olivocochlear neurons can also be activated by sounds through a brainstem reflex circuit. Whether the individual variability of this reflex is related to the cognitive capacity to suppress auditory stimuli is still controversial. Here we propose that the individual strength per animal of the olivocochlear reflex is correlated with the ability to suppress auditory distractors during visual attention in awake chinchillas. The olivocochlear reflex was elicited with a contralateral broad-band noise at ~ 60 dB and ipsilateral distortion product otoacoustic emissions were obtained at different frequencies (1–8 kHz). Fourteen chinchillas were evaluated in a behavioural protocol of visual attention with broad-band noise and chinchilla vocalizations as auditory distractors. Results show that the behavioural performance was affected by both distractors and that the magnitudes of the olivocochlear reflex evaluated at multiple frequencies were relevant for behavioural performance during visual discrimination with auditory distractors. These results stress the ecological relevance of the olivocochlear system for suppressing natural distractors.

Drug addictions are chronic mental disorders characterized by compulsive drug seeking and drug use, despite their negative consequences. It is a priority to find therapeutic alternatives to prevent relapse, as there are still no treatments that can ensure abstinence. One of the neural systems implicated in the appearance of the states of discomfort that motivate relapse is the interoceptive system, which oversees our internal body states. However, less attention has been given to the peripheral components of the interoceptive system and their role in addictions. Within these pathways, the vagus nerve represents one of the main visceral afferents of the interoceptive system. We hypothesized that the interruption of visceral afferent pathways would decrease the motivational effects of the drug, thereby either decreasing or preventing drug cravings. To test this idea, we used rats of a highalcohol-drinking line and measured the effect that vagus nerve resection had on the relapse-like alcohol drinking, expressed as the alcohol deprivation effect, a phenomenon that has been linked to addiction-related events such as alcohol cravings. We found that even though vagotomy completely eliminates the effect of alcohol deprivation, it has no impact on water consumption or animal weight. These results give us valuable information about the relationship between the autonomic nervous system and alcohol use disorders and allow us to propose new clinical research that might have translational options.

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