Single session of cocaine intravenous self-administration shapes goal-oriented behaviours and up-regulates Arc mRNA levels in rat medial prefrontal cortex

Fabio Fumagalli, Carlotta Franchi, Lucia Caffino, Giorgio Racagni, Marco A. Riva, Luigi Cervo

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

To separate the direct pharmacological effects of cocaine from those associated with active drug self-administration we employed a yoked control-operant paradigm and investigated the expression of well established markers of the rapid action of cocaine, i.e. the inducible early genes Arc and Zif268 and trophic factors, i.e. brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF-2), in rats after a single intravenous (i.v.) cocaine self-administration session. Animals self-administering cocaine (SA, 0.25 mg/0.1 ml saline per infusion, 2-h session) did more active lever-presses than yoked-cocaine (YC) and yoked-vehicle (YV) animals. This goal-oriented behaviour was accompanied by a selective increase in Arc mRNA levels in the medial prefrontal cortex (mPFC). There were no changes in the expression of the other genes in this brain region. mRNA levels of Arc and Zif268 in striatum and Zif268 in the nucleus accumbens markedly increased both in SA and YC animals; but there was no change in the expression of FGF-2 and BDNF. No changes were observed in hippocampus, hypothalamus, frontal cortex, and midbrain in SA and YC animals compared to YV animals in any of the genes. These findings demonstrate that a single session of cocaine i.v. self-administration is sufficient to shape rat behaviour towards goal-directed behaviours and selectively up-regulate Arc expression in mPFC (of SA animals), providing the first evidence that the mPFC's function is already profoundly influenced by the first voluntary cocaine exposure.

Original languageEnglish
Pages (from-to)423-429
Number of pages7
JournalInternational Journal of Neuropsychopharmacology
Volume12
Issue number3
DOIs
Publication statusPublished - Apr 2009

Fingerprint

Self Administration
Prefrontal Cortex
Cocaine
Intravenous Administration
Up-Regulation
Messenger RNA
Fibroblast Growth Factor 2
Brain-Derived Neurotrophic Factor
Nucleus Accumbens
Frontal Lobe
Mesencephalon
Genes
Hypothalamus
Hippocampus
Pharmacology
Gene Expression
Brain

Keywords

  • Cocaine
  • Inducible early genes
  • Neurotrophins

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health
  • Medicine(all)

Cite this

Single session of cocaine intravenous self-administration shapes goal-oriented behaviours and up-regulates Arc mRNA levels in rat medial prefrontal cortex. / Fumagalli, Fabio; Franchi, Carlotta; Caffino, Lucia; Racagni, Giorgio; Riva, Marco A.; Cervo, Luigi.

In: International Journal of Neuropsychopharmacology, Vol. 12, No. 3, 04.2009, p. 423-429.

Research output: Contribution to journalArticle

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