Biology subjects

Giuliano, C.

Publications and source records attributed to Giuliano, C..

3 recordsLinked to original sources

bioRxiv2021

Maladaptive cue-controlled cocaine-seeking habits promote increased relapse severity in rats.

The inflexible pursuit of drug-seeking and great tendency to relapse that characterize addiction has been associated with the recruitment of the dorsolateral striatum-dependent habit system. However, the mechanisms by which maladaptive drug-seeking habits influence subsequent relapse are obscure. Here, we show that rats with a long history of cocaine-seeking, controlled by drug-paired cues and mediated by the habit system, show highly exacerbated drug-seeking at relapse that is not mediated by cocaine withdrawal. This heightened tendency to relapse is underpinned by transient engagement of the dorsomedial striatum goal-directed system and reflects emergent negative urgency resulting from the prevention of enacting the seeking habit during abstinence. These results reveal a novel mechanism underlying the pressure to relapse and indicate a target for preventing it. One Sentence SummaryInstrumental deprivation triggers flexibility in the well-established cue-controlled cocaine-seeking behaviour.

neuroscience↗

bioRxiv2020

Individual differences in the engagement of habitual control over alcohol seeking predicts the development of compulsive alcoholseeking and drinking

Excessive drinking is an important behavioural characteristic of alcohol addiction, but not the only one. Individuals addicted to alcohol crave alcoholic beverages, spend time seeking alcohol despite negative consequences, and eventually drink to intoxication. With prolonged use, control over alcohol seeking devolves to anterior dorsolateral striatum, dopamine-dependent mechanisms implicated in habit learning and individuals in whom alcohol-seeking relies more on these mechanisms are more likely to persist in seeking alcohol despite the risk of punishment. Here, we tested the hypothesis that the development of habitual alcohol-seeking predicts the development of compulsive seeking and that, once developed, it is associated with compulsive alcohol drinking. Male alcohol-preferring rats were pre-exposed intermittently to a two-bottle choice procedure, and trained on a seeking-taking chained schedule of alcohol reinforcement until some individuals developed punishment-resistant seeking behaviour. The associative basis of their seeking responses was probed with an outcome-devaluation procedure, early or late in training. After seeking behaviour was well established, subjects that had developed greater resistance to outcome-devaluation (were more habitual) were more likely to show punishment-resistant (compulsive) alcohol seeking. These individuals also drank more alcohol, despite quinine adulteration, even though having similar alcohol preference and intake before and during instrumental training. They were also less sensitive to changes in the contingency between seeking responses and alcohol outcome, providing further evidence of recruitment of the habit system. We therefore provide direct behavioural evidence that compulsive alcohol seeking emerges alongside compulsive drinking in individuals that have preferentially engaged the habit system.

neuroscience↗

bioRxiv2020

Environment-dependent behavioral traits and experiential factors shape addiction vulnerability

The transition from controlled drug use to drug addiction depends on an interaction between a vulnerable individual, their environment and a drug. Here we tested the hypothesis that conditions under which individuals live influence behavioral vulnerability traits and experiential factors operating in the drug taking environment to determine the vulnerability to addiction. The role of behavioural vulnerability traits in mediating the influence of housing conditions on the tendency to acquire cocaine self-administration was characterised in 48 rats housed in either an enriched (EE) or a standard (SE) environment. Then, the influence of these housing conditions on the individual vulnerability to develop addiction-like behaviour for cocaine or alcohol was measured in 72 EE or SE rats after several months of cocaine self-administration or intermittent alcohol drinking, respectively. The determining role of negative experiential factors in the drug taking context was further investigated in 48 SE rats that acquired alcohol drinking as a self-medication strategy. The environment influenced the acquisition of drug intake through its effect on behavioral markers of resilience to addiction. In contrast, the initiation of drug taking as a coping strategy or in a negative state occasioned by the contrast between enriched housing conditions and a relatively impoverished drug taking setting, facilitated the development of compulsive cocaine and alcohol intake. These data demonstrate that addiction vulnerability depends on environmentally determined experiential factors, suggesting that initiating drug use through negative reinforcement-based self-medication facilitates the development of addiction in vulnerable individuals. Significance StatementThe factors that underlie an individuals vulnerability to switch from controlled, recreational drug use to addiction are not well understood. We showed that in individuals housed in enriched conditions, the experience of drugs in the relative social and sensory impoverishment of the drug taking context, and the associated change in behavioural traits of resilience to addiction, exacerbate the vulnerability to develop compulsive drug intake. We further demonstrated that the acquisition of alcohol drinking as a mechanism to cope with distress increases the vulnerability to develop compulsive alcohol intake. Together these results demonstrate that experiential factors in the drug taking context shape the vulnerability to addiction.

neuroscience↗