High anxiety is a predisposing endophenotype for loss of control over cocaine, but not heroin, self-administration in rats

Abstract

The present data suggest that high anxiety predisposes rats to lose control over cocaine-but not heroin-intake. High anxiety may therefore be a vulnerability trait for the escalation of stimulant but not opiate self-administration.

High Locomotor Reactivity to Novelty Is Associated with an Increased Propensity to Choose Saccharin Over Cocaine: New Insights into the Vulnerability to Addiction

“…In the present study, we used multiple behavioral assays in a longitudinal approach to investigate whether the sensitivity to an alternative reinforcer was associated with behavioral traits-elevated response to novelty (Piazza et al, 1989;, high anxiety (Dilleen et al, 2012), and enhanced sensitivity to the salience of environmental stimuli (Saunders et al, 2013)-that have themselves been Figure 8 Rats readily choose cocaine but high responders prefer saccharin. The overall population of rat preferred cocaine over a sweet solution of saccharin (a).…”

“…Then, animals were ranked according to their performance and, given that no objective physical criteria could be applied on the distributions to identify subpopulations (such as a bimodal distribution, see Belin et al, 2011 for further details), the upper and lower quartiles were selected for between-subject analyses as previously described (Belin et al, , 2011Dilleen et al, 2012). This approach identifies homogenous populations, maximizes differences between these populations, limits type I errors, and prevents type II errors (Cain et al, 2005).…”

“…We and others have identified behavioral traits in rats, such as high anxiety, that predict both increased motivation for cocaine (Homberg et al, 2002) and increased vulnerability to switch from controlled to escalated cocaine self-administration (Dilleen et al, 2012). These factors contributing to the development of addiction-like behaviors have been shown to be, at least partly, dissociable (Belin et al, , 2011Molander et al, 2011) from factors that instead predict an increased sensitivity to the associative and motivational properties of cocaine (Flagel et al, 2008;Robinson and Flagel, 2009;Meyer et al, 2012b) and a greater propensity to acquire cocaine self-administration , namely the sign-tracking (Tomie et al, 1989(Tomie et al, , 2008 and high locomotor response to novelty traits (Piazza et al, 1989), respectively.…”

The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking

“…EtOH-naive animals were assessed for anxiety on the EPM as previously described (Dilleen et al, 2012). See Supplementary Information.…”

Animal Models of Drug Addiction

“…These data suggest that if high anxiety trait may contribute to the choice of the drug used, i.e., preference for alcohol or opiates [210], it does not necessarily contribute to the development of compulsive use when the drug is initially used as a self-medication [211]. However, the striking relationship between high anxiety levels in the EPM and subsequent vulnerability to escalate cocaine intake suggest that high anxiety may facilitate a tolerance to anxiogenic properties of cocaine [212] perhaps because of a ceiling effect, or, instead enhance the potential anxiolytic properties of cocaine that have been suggested for low doses of the drug [213].…”