Amphetamine withdrawal modulates FosB expression in mesolimbic dopaminergic target nuclei: Effects of different schedules of administration

Carol A. Murphy, Holger Russig, Marie Astrid Pezze, Boris Ferger, Joram Feldon

Research output: Contribution to journalArticlepeer-review

Abstract

Different patterns of psychostimulant intake can elicit widely varying behavioral and neurochemical consequences. Accordingly, rats were studied during withdrawal from either of two schedules of amphetamine administration, one consisting of 6 days of low-dose (1.5 mg/kg, i.p.) daily intermittent (INT) amphetamine (AMPH) injections, and the other of 6 days of moderately high-dose (1-5 mg/kg, i.p.) escalating (ESC) AMPH injections, for the effects of these treatments on numbers of FosB-positive nuclei and monoamine utilization in dopaminergic target areas. Withdrawal from AMPH pretreatment according to the ESC schedule markedly increased FosB expression in the nucleus accumbens shell and basolateral amygdala. In contrast, withdrawal from INT-AMPH administration did not increase FosB expression in any of the regions examined. Post-mortem neurochemical analyses of these same brain regions did not reveal effects of withdrawal from either INT or ESC administration of AMPH. These results suggest that withdrawal from a moderately high-dose AMPH regimen modifies patterns of gene expression in mesocorticolimbic dopaminergic target nuclei without significantly affecting basal monoamine levels. The strength of these effects in the nucleus accumbens shell and basolateral nucleus of the amygdala are consistent with behavioral and clinical data indicating the importance of these areas in the neuroadaptive changes which characterize addiction and withdrawal states.

Original languageEnglish
Pages (from-to)926-939
Number of pages14
JournalNeuropharmacology
Volume44
Issue number7
DOIs
StatePublished - Jun 2003
Externally publishedYes

Keywords

  • Addiction
  • Amygdala
  • Dopamine
  • Nucleus accumbens
  • Prefrontal cortex
  • Striatum

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