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BEHAVIORAL PHARMACOLOGY

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

Neurobehavioral Laboratory, Division of Substance Abuse, Yale University School of Medicine, West Haven, Connecticut (T.A.K., X.Y.Z.); and School of Biological Sciences, University of California, Irvine, California (P.K.)

Our research demonstrates that neonatal isolation (ISO; 1 h/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 nonhandled (NH) control conditions. In experiment 1, microdialysis probes were aimed at accumbens core and separate groups administered vehicle or cocaine (5 and 10 mg/kg i.p.). Samples were analyzed for DA levels via high-performance liquid chromatography. In experiment 2, ISO and NH rats were administered one of these cocaine doses, and locomotor activity was assessed. Effects of cocaine (0.3–30 mg/kg), the D₁ antagonist SCH23390[R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (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. Furthermore, the D₂, but not D₁, antagonist disrupted behavior to a greater extent in ISO versus 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.

Address correspondence to: Dr. Therese A. Kosten, Division of Substance Abuse, Yale University School of Medicine, VA Connecticut Hospital System, 950 Campbell Ave., Bldg. 5, 3rd Floor, West Haven, CT 06516. E-mail: therese.kosten{at}yale.edu

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