Environment-dependent behavioral traits and experiential factors shape addiction vulnerability

Eur J Neurosci. 2021 Mar;53(6):1794-1808. doi: 10.1111/ejn.15087. Epub 2021 Jan 12.


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 behavioral vulnerability traits in mediating the influence of housing conditions on the tendency to acquire cocaine self-administration was characterized 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 behavior 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 to self-medicate distress in a schedule-induced polydipsia procedure. 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 indicate that addiction vulnerability depends on environmentally determined experiential factors, and suggest that initiating drug use through negative reinforcement-based self-medication facilitates the development of addiction in vulnerable individuals. SIGNIFICANCE STATEMENT: The factors that underlie an individual's 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 behavioral 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.

Keywords: alcohol; cocaine; compulsivity; environmental enrichment; schedule-induced polydipsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Addictive*
  • Cocaine*
  • Cocaine-Related Disorders*
  • Rats
  • Reinforcement, Psychology
  • Self Administration


  • Cocaine