Original Article

Neuropsychopharmacology (2006) 31, 70–76. doi:10.1038/sj.npp.1300779; published online 1 June 2005

Preclinical Research

Heightened Cocaine and Food Self-Administration in Female Rats with Neonatal Isolation Experience

Therese A Kosten1, Xiang Yang Zhang1 and Priscilla Kehoe2

  1. 1Division of Substance Abuse, Yale University School of Medicine, VA-CT Hospital System, West Haven, CT, USA
  2. 2School of Biological Sciences, University of California Irvine, CA, USA

Correspondence: Dr TA Kosten, Division of Substance Abuse, Yale University School of Medicine, VA-CT Hospital System, 950 Campbell Avenue, Building 5, 3rd Floor, West Haven, CT 06516, USA. Tel: +1 203 932 5711 x5100; Fax: +1 203 937 4915; E-mail: therese.kosten@yale.edu

Received 1 November 2004; Revised 8 February 2005; Accepted 13 April 2005; Published online 1 June 2005.

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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.

Keywords:

maternal separation, stress, sex differences, operant behavior, progressive ratio

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