Neurochemical and behavioral responses to cocaine in adult male rats with neonatal isolation experience.
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 D(1) 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 D(2) 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 D(2), but not D(1), 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 D(2) antagonist may reflect decreased levels of this receptor type as we showed previously in infant rats.
Kosten
Therese A
TA
Division of Substance Abuse, Yale University School of Medicine, VA Connecticut Hospital System, 950 Campbell Avenue, Bldg. 5, 3rd Floor, West Haven, CT 06516, USA. therese.kosten@yale.edu
Zhang
Xiang Yang
XY
Kehoe
Priscilla
P
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D003042:Cocaine / Q000097:blood / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012646:Self Administration; D012934:Social Isolation
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003042:Cocaine; D004298:Dopamine