Elsevier

Neuroscience

Volume 129, Issue 2, 2004, Pages 415-424
Neuroscience

Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: A microdialysis study

https://doi.org/10.1016/j.neuroscience.2004.08.010Get rights and content

Abstract

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.

Section snippets

Animals

Adult male Long-Evans rats (275–300 g; Charles River, Lachine, PQ, Canada) were used in this study. Rats were singly housed in a reversed light/dark cycle colony room (lights off between 07:00 h and 19:00 h) and maintained in a constant temperature and humidity controlled animal facility with food and water available ad libitum. Animal care and experimental procedures were carried out in compliance with the guidelines of the Canadian Council on Animal Care (compatible with NIH guidelines), and

Nicotine infusions in different sessions

Five to six nicotine infusions in a given session were considered the criteria for acquisition of nicotine self-administration in this study (Corrigall et al., 1992, 1994). In fact, very few animals (one to two) failed to meet these criteria. Therefore, only those rats that acquired self-administration and had correct probe placements (see below) were included in this study. The number of infusions/session (mean±S.E.M.) in nicotine self-administration (n=20) and yoked nicotine (n=12) groups

Discussion

The important findings in this study are i) the basal extracellular DA levels in the ACB are reduced after abstinence from nicotine self-administration (Figs. 2 and 3A); ii) the extracellular DA levels and in vivo extraction fractions in the yoked nicotine groups are not significantly different from the nicotine self-administration group (Figs. 2 and 3B). Similarly, a reduction in basal DA levels was also evident in the difference in baseline levels observed in the conventional microdialysis

Acknowledgments

The authors thank Dr. William J. McBride for his advice and critical comments on the manuscript and Dr. Richard J. Thielen for help in statistical analysis. This research was supported by NIH/NIDA grant DA 09577.

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    Present address: Corrigall Consulting, Thornhill, Ontario, Canada.

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