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Updated: Aug 17, 2026
A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
Heightened cocaine and food self-administration in female rats with neonatal isolation experience
Therese A Kosten1, Xiang Yang Zhang, Priscilla Kehoe
1Division of Substance Abuse, Yale University School of Medicine, VA-CT Hospital System, West Haven, CT, USA. theresekosten@yale.
Insights
Early life stress from neonatal isolation enhances drug and food seeking in adult female rats, even after behavior is established. This suggests lasting impacts of early stress on reward system function.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Developmental Psychology
Background:
- Early life stress, specifically neonatal isolation, has been shown to facilitate the initial learning (acquisition) of drug and food self-administration in adult female rats.
- This study investigates whether neonatal isolation also impacts established operant behaviors, extending previous findings on acquisition.
Purpose of the Study:
- To determine if neonatal isolation enhances responding for cocaine and food reinforcers in adult female rats after operant performance has been established.
- To examine the effects of neonatal isolation on responding under fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement.
Main Methods:
- Adult female rats were exposed to neonatal isolation (1 hr/day, postnatal days 2-9) or handled (control).
- Experiment 1: Rats trained to self-administer cocaine were tested under FR3 and PR schedules with varying cocaine doses.
- Experiment 2: Rats trained for food self-administration were tested under two PR schedules.
Main Results:
- Neonatal isolation significantly enhanced responding for cocaine under both FR and PR schedules.
- Neonatal isolation increased responding for food under a PR schedule.
- These findings indicate that neonatal isolation enhances responding under maintenance conditions for both drugs and food.
Conclusions:
- Neonatal isolation induces enduring behavioral changes that enhance responding for rewards, extending beyond the initial acquisition phase.
- These effects may be linked to neonatal isolation's previously demonstrated ability to increase striatal dopamine responses to psychostimulants.
- Early life stress has long-lasting consequences on reward-related behaviors and neurobiology.
Abstract:
Previously, we demonstrated that the early life stress of neonatal isolation facilitates acquisition of cocaine and food self-administration in adult female rats. We now test whether it enhances responding for these reinforcers after operant performance is established. Adult female rats were derived from litters that were either subjected to neonatal isolation (1 h/day isolation; postnatal days 2-9) or were nonhandled and assigned to one of two experiments. In Experiment 1, female rats well trained to self-administer cocaine were tested under a fixed-ratio 3 (FR3) schedule with several cocaine doses (0.0625-1.0 mg/kg/infusion) and under a progressive-ratio (PR) schedule (0, 0.5, and 1.0 mg/kg/infusion cocaine). In Experiment 2, female rats well trained to respond for food reinforcers under an FR15 schedule were tested under two PR schedules. Results show that neonatal isolation enhanced responding for cocaine under both schedules of reinforcement and increased responding for food under a PR schedule of reinforcement. These data extend our previous acquisition study in female rats to show that neonatal isolation enhances responding under maintenance conditions. These enduring behavioral changes may relate to the ability of neonatal isolation to increase striatal dopamine responses to psychostimulants, effects we showed previously in infant and juvenile rats. Neuropsychopharmacology (2006) 31, 70-76. doi:10.1038/sj.npp.1300779; published online 1 June 2005.
