| Neuroadaptations in the mesocorticolimbic dopamine system, particularly the nucleus accumbens (NAc), are intricately involved in cocaine addiction. Two main regions of the NAc, called the core and the shell, are differentially involved in various aspects of the addiction process. Since excitability largely determines the function of a neuron, I hypothesized that NAc core and shell medium spiny neurons exhibit differences in excitability with repeated cocaine administration. Thus, parameters of excitability, such as action potential (AP) properties, inward rectification, outward rectification and evoked firing were measured in the core and shell after short term (3--4 days) and long term (2--3 weeks) withdrawal from repeated cocaine pretreatment (five days of once daily injection of 15mg/kg i.p.).;After 3--4 days of withdrawal, all measured indices of excitability were decreased in the NAc core but not in the shell. AP threshold was increased, AP amplitude was decreased, inward and outward rectification was increased, and evoked spikes were decreased in the core.;After 2--3 weeks of withdrawal basal suprathreshold excitability was increased in the NAc core, while it was partially decreased in the shell. In the core, AP threshold was decreased, AP amplitude was increased and evoked spikes were decreased, whereas in the shell only AP amplitude was decreased. Inward and outward rectification was not altered in both core and shell.;Re-exposure to a single injection of cocaine after 2--3 weeks of withdrawal abolished the increased excitability of the core, and caused further reduction of excitability in the shell. In the core, AP threshold, AP amplitude and outward rectification were decreased resulting in no change in evoked spikes. In the shell, AP threshold and AP amplitude was decreased, while outward rectification was increased resulting in decreased evoked firing.;The changes in excitability of the core suggest a possible role in short term cocaine withdrawal effects of anhedonia, anergia and tolerance to cocaine reward, as well as the long term withdrawal effects cue-induced cocaine seeking. The changes in excitability of the shell suggest a possible role in cocaine-induced cocaine seeking and craving. |
