Escalation of Drug Use

Abstract

Among the different behavioral criteria used to discriminate substance dependence (or drug addiction) from other non-disordered forms of drug use, drug intake escalation presents a number of unique features that makes it particularly suitable for modeling in nonhuman animals. This criterion has stood the passage of time despite major revisions of diagnostic systems, it is common to all known drugs of abuse and it can be readily and unambiguously operationalized in laboratory animals. Here I exhaustively review evidence showing that escalation to heavy consumption of different drugs (except perhaps nicotine) can be rapidly induced in the majority of individual animals (i.e., rats) by increased drug availability. Such an escalation of drug use is probably paralleled by an authentic escalation to drug addiction, as it is associated with the co-occurrence of other addiction-like changes (i.e., increased motivation for drug use; increased difficulty to abstain from drug use; decreased sensitivity to negative consequences). In addition, during escalation of drug intake, most individual animals become increasingly responsive to drug-and stress-primed, but apparently not cue-primed, reinstatement of drug seeking after extinction. Finally, following increased drug use, most individuals present selective cognitive dysfunctions (e.g., deficits in executive functions) that may contribute to the establishment and/or persistence of addiction. Thus, the study of individuals with escalating patterns of drug use should provide a unique and valid approach to investigate, experimentally, the behavioral and neurobiological mechanisms that underlie the progression to addiction.

Cracking the Molecular Code of Cocaine Addiction

“…SEM, standard error of the mean Finally, using a conditioned emotional suppression procedure, Vanderschuren and Everitt (2004) found that after extended drug use rats were more likely to continue to seek cocaine despite the presence of a danger signal that normally suppresses operant behavior. Similarly, we recently found that after punishment by footshock rats with extended access to cocaine resumed drug self-administration more rapidly than controls, which refrained from self-administering cocaine for at least 3 consecutive days (Ahmed 2011).…”

“…Escalation of cocaine intake is largely due to acceleration in the rate of cocaine self-administration. Adapted and modifi ed from Ahmed (2005Ahmed ( , 2011. SEM, standard error of the mean Finally, using a conditioned emotional suppression procedure, Vanderschuren and Everitt (2004) found that after extended drug use rats were more likely to continue to seek cocaine despite the presence of a danger signal that normally suppresses operant behavior.…”

“…Escalation of drug use, a hallmark stage in the transition to addiction (Ahmed 2011), was one of the fi rst behavioral features of addiction documented in rats with extended access to cocaine but not in control rats with limited access to the drug (Ahmed and Koob 1998) (Figure 1). Specifi cally, rats with extended access gradually increased intake (both total and hourly) whereas among rats with limited access intake remained remarkably stable, even after several months (Ahmed and Koob 1999).…”

“…We focus on a robust modeling strategy that consists of comparing and contrasting rats with a history of extended versus limited access to cocaine for self-administration (Ahmed 2011;Ahmed and Koob 1998).…”

A redescription of data does not count as a general theory

“…Ironically, however, by focusing attention on drug use initiation, this model has contributed, perhaps more than any other models, to blur the distinction between mere drug use and addiction and thus retard progress in this area. If anything, the LR-HR model may be considered a model of transition from initial abstinence to recreational drug use, but certainly not a model of transition to escalated drug use (Ahmed 2011;Ahmed and Koob 1998). It remains to be demonstrated whether HR rats are more vulnerable than LR rats to escalation of drug use under extended access conditions.…”