Amphetamine withdrawal modulates FosB expression in mesolimbic dopaminergic target nuclei: effects of different schedules of administration.
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.
Behavioral Neurobiology Laboratory, Swiss Federal Institute of Technology (ETH-Zurich), Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland. murphy@behav.biol.ethz.ch
Carol A
CA
Murphy
Holger
H
Russig
Marie-Astrid
MA
Pezze
Boris
B
Ferger
Joram
J
Feldon
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D000697:Central Nervous System Stimulants; D018377:Neurotransmitter Agents; D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; D003913:Dextroamphetamine; D004298:Dopamine