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Neurochemical and behavioral responses to cocaine in adult male rats with neonatal isolation experience.
J Pharmacol Exp Ther. 2005 Aug; 314(2):661-7.JP

Abstract

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.

Authors+Show Affiliations

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.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15845857

Citation

Kosten, Therese A., et al. "Neurochemical and Behavioral Responses to Cocaine in Adult Male Rats With Neonatal Isolation Experience." The Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 2, 2005, pp. 661-7.
Kosten TA, Zhang XY, Kehoe P. Neurochemical and behavioral responses to cocaine in adult male rats with neonatal isolation experience. J Pharmacol Exp Ther. 2005;314(2):661-7.
Kosten, T. A., Zhang, X. Y., & Kehoe, P. (2005). Neurochemical and behavioral responses to cocaine in adult male rats with neonatal isolation experience. The Journal of Pharmacology and Experimental Therapeutics, 314(2), 661-7.
Kosten TA, Zhang XY, Kehoe P. Neurochemical and Behavioral Responses to Cocaine in Adult Male Rats With Neonatal Isolation Experience. J Pharmacol Exp Ther. 2005;314(2):661-7. PubMed PMID: 15845857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurochemical and behavioral responses to cocaine in adult male rats with neonatal isolation experience. AU - Kosten,Therese A, AU - Zhang,Xiang Yang, AU - Kehoe,Priscilla, Y1 - 2005/04/21/ PY - 2005/4/23/pubmed PY - 2005/10/1/medline PY - 2005/4/23/entrez SP - 661 EP - 7 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 314 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15845857/Neurochemical_and_behavioral_responses_to_cocaine_in_adult_male_rats_with_neonatal_isolation_experience_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15845857 DB - PRIME DP - Unbound Medicine ER -