Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: a microdialysis study.
There is little evidence to date to indicate if mesoaccumbens dopamine function at the neurochemical level is altered during early abstinence from chronic i.v. nicotine self-administration. Thus, a quantitative microdialysis (no-net-flux) approach was used to measure basal extracellular concentrations and extraction fractions of dopamine in the nucleus accumbens (ACB) of rats that self-administered nicotine i.v. for 25 days, as well as in rats serving as yoked comparison groups (yoked nicotine and yoked saline). After 24-48 h of the final self-administration session, there was a significant reduction in basal extracellular dopamine levels in the ACB of the self-administration group compared with the yoked saline group (1.35+/-0.15 nM versus 3.70+/-0.28 nM). The basal extracellular dopamine levels in the yoked nicotine group (1.46+/-0.20 nM) were not significantly different compared with the nicotine self-administration group. The in vivo extraction fraction of dopamine, an indirect measure of dopamine uptake, was significantly increased in the nicotine self-administration (86%) and yoked nicotine (91%) groups compared with the yoked saline group (77%). In addition, a marked reduction in the elevation of extracellular dopamine levels in the ACB occurred after a nicotine challenge as measured by conventional microdialysis in the self-administration (112% of basal) and yoked nicotine (121% of basal) groups as compared with a yoked saline (154% of basal) group. The reduced basal ACB dopamine levels in the nicotine groups during early abstinence appears to be due to increased clearance, suggesting increased dopamine uptake is occurring as a result of the chronic nicotine treatment. The reduced elevation of extracellular dopamine levels in the ACB upon nicotine challenge suggests a functional desensitization or downregulation phenomenon involving acetylcholine receptors (nicotinic nAChRs). Overall, these results provide clear evidence for a neuroadaptive change that alters dopamine transmission in the ACB during abstinence from chronic i.v. nicotine exposure.
Rahman
S
S
Smoking and Nicotine Dependence Research, Neuroscience Department, Centre for Addiction and Mental Health, University of Toronto, 33 Russell Street, Toronto, Ontario, M5S 2S1 Canada. shafiq_rahman@camh.net
Zhang
J
J
Engleman
E A
EA
Corrigall
W A
WA
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D009435:Synaptic Transmission
D018722:Nicotinic Agonists; D009538:Nicotine; D004298:Dopamine