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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on April 21, 2005; DOI: 10.1124/jpet.104.081216

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Received for publication November 30, 2004.
Revised April 18, 2005.
Accepted for publication April 19, 2005.

Neurochemical and Behavioral Responses to Cocaine in Adult Male Rats with Neonatal Isolation Experience

Therese A. Kosten 1*, Xiang Yang Zhang 1, Priscilla Kehoe 2

1 Yale University School of Medicine 2 University of California at Irvine

* Address correspondence to: E-mail: therese.kosten{at}yale.edu

Abstract

Our research demonstrates that neonatal isolation (ISO; 1 hr/day isolation; Postnatal days 2-9) enhances extracellular, ventral striatal dopamine (DA) responses to psychostimulants in infant and juvenile rats. In adult rats, we find ISO facilitates acquisition and maintenance of cocaine self-administration. We now test whether ISO enhances cocaine-induced accumbens DA levels in adults using in vivo microdialysis. Behavioral responses to cocaine and DA antagonists were also examined. Adult male rats were derived from litters subjected to ISO or non-handled (NH) control conditions. In Experiment 1, microdialysis probes were aimed at accumbens core and separate groups administered vehicle or cocaine (5, 10 mg/kg; IP). Samples were analyzed for DA levels via HPLC. In Experiment 2, ISO and NH rats were administered one of these cocaine doses and locomotor activity assessed. Effects of cocaine (0.3-30 mg/kg), the D1 antagonist, SCH 23390 (0.003-0.03 mg/kg), and the D2 antagonist, eticlopride (0.01-0.1 mg/kg) on disruption of responding for food were examined in Experiment 3. Cocaine plasma levels were assessed in Experiment 4. ISO enhanced cocaine-induced increases in accumbens DA levels. Further, the D2, but not D1, antagonist disrupted behavior to a greater extent in ISO vs NH rats. Yet, ISO did not significantly alter behavioral responses to cocaine or cocaine plasma levels. These data show that the ability of ISO to enhance accumbens DA responses to cocaine endures into adulthood. Moreover, that ISO rats are more sensitive to a D2 antagonist may reflect decreased levels of this receptor type as we showed previously in infant rats.


Key words: DA receptor subtypes, early life stress, locomotor activity, maternal separation, nucleus accumbens, schedule-controlled responding


This article has been cited by other articles:


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[Abstract] [Full Text] [PDF]


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