Figure 1
Experimental timeline for phenotyping of addiction vulnerable and resilient groups. (a) To phenotype animals into addiction vulnerable or resilient groups, animals were first implanted with an intravenous (i.v.) catheter and trained to self-administer cocaine (0.25 mg per 0.1 ml intravenously) on an FR1 schedule of responding which progressed to an FR3 and finally an FR5 schedule of responding. Animals were then tested for inability to refrain from drug seeking during periods of signalled drug non-availability (NDA) for 5 days. Following this, animals were tested for motivation to consume drug using a progressive ratio test, followed by a final FR5 cocaine session. Drug-seeking behavior was then extinguished by exposing animals to the operant chamber. Drug was absent and lever pressing did not result in a drug reward. Once responding returned to baseline levels, animals were re-exposed to cues associated with drug availability in a reinstatement test and killed 24h later. Animals that scored in the top third of the distribution for each behavioral test were deemed to be addiction vulnerable, whereas those in the bottom third of the distribution were identified as addiction resilient. For detailed description of behavioral training and phenotyping, see Brown et al. (2010). (b) Animals phenotyped as addiction vulnerable showed significantly higher NDA responding, PR breakpoint and reinstatement scores that animals phenotyped as addiction resilient.
