Changes in basal and cocaine-evoked extracellular dopamine uptake and release in the rat nucleus accumbens during early abstinence from cocaine: quantitative determination under transient conditions

doi:10.1016/S0306-4522(02)00099-4

Neuroscience

Volume 112, Issue 4, 19 July 2002, Pages 907-919

https://doi.org/10.1016/S0306-4522(02)00099-4 Get rights and content

Abstract

Despite an abundance of studies on mechanisms of behavioral sensitization, considerable uncertainty exists as to whether alterations in dopamine neurotransmission underlie the exacerbated behavioral effects of cocaine observed during the early stages of abstinence. One of the factors contributing to the uncertainty and controversy may be the limitations in utilized measurement techniques (mostly conventional microdialysis). The techniques of quantitative microdialysis under transient conditions and rotating disk electrode voltammetry were used to characterize basal dopamine dynamics as well as time-related changes in extracellular dopamine concentrations and dopamine uptake that occur in response to an acute drug challenge in control animals and animals with previous history of cocaine.

Basal extracellular dopamine concentrations were unaltered on abstinence day 3 from repeated cocaine administration (5 days, 20 mg/kg, i.p.). The extraction fraction of dopamine, an indirect measure of dopamine uptake, was significantly lower in cocaine-sensitized animals relative to controls. These two facts, taken together, suggest that basal dopamine release is depressed in cocaine-sensitized animals on abstinence day 3. At the same time, a cocaine challenge decreased the extraction fraction and increased the extracellular dopamine concentration in both experimental groups. The magnitude of the increase in extracellular dopamine concentration was greater in cocaine-sensitized animals, while the ability of cocaine to decrease the extraction fraction was unaltered, suggesting that the increase in extracellular dopamine concentration reflects an increase in drug-evoked dopamine release. Moreover, cocaine-pretreated rats demonstrated greater depolarization-induced dopamine release and the ability of dopamine D₂ receptor agonist, quinpirole, to inhibit release was decreased in these animals.

These data demonstrate that a cocaine treatment regimen resulting in behavioral sensitization is associated with a reduction in basal dopamine release, an enhancement in both cocaine and K⁺-evoked dopamine release, and a subsensitivity of dopamine D₂ autoreceptors that regulate dopamine release in the nucleus accumbens.

Section snippets

Animals

Male Sprague–Dawley rats (Charles River Laboratories, USA) weighing 250–300 g were housed in groups of three per cage for at least 1 week before use. They were maintained in a temperature- and humidity-controlled environment under an artificial 12-h light/dark cycle with laboratory rat chow and water available ad libitum. All cocaine injections and microdialysis experiments were performed during the light cycle. Animals used in this study were maintained in facilities accredited by the American

Effect of cocaine treatment on basal and cocaine-evoked DA release and uptake during early stages of abstinence (abstinence day 3)

Figure 1 shows no net flux plots for control animals prior to and following the acute cocaine challenge (20 mg/kg; i.p.). Each plot represents combined data obtained from the three groups of animals (DA_in: 0, 10 or 40 nM) during each 10-min sampling interval. The extracellular concentration of DA (the point where DA_in−DA_out=0) and the extraction fraction (slope of the linear regression) for each sampling interval were then plotted together to show a time course of extracellular DA concentration

Discussion

The results of the present studies demonstrate that the early phase of abstinence from repeated cocaine administration is associated with marked alterations in basal and cocaine-evoked DA neurotransmission in the NAcc of behaviorally sensitized animals. Basal extracellular DA concentrations were unaltered 3 days following the cessation of repeated cocaine administration. The extraction fraction of DA, an indirect measure of DA uptake, was significantly decreased relative to control animals.

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Changes in basal and cocaine-evoked extracellular dopamine uptake and release in the rat nucleus accumbens during early abstinence from cocaine: quantitative determination under transient conditions

Abstract

Section snippets

Animals

Effect of cocaine treatment on basal and cocaine-evoked DA release and uptake during early stages of abstinence (abstinence day 3)

Discussion

Brain Res.

Biol. Psychiatry

Life Sci.

Neuroscience

Neurosci. Lett.

J. Neurosci. Methods

Brain Res. Dev. Brain Res.

Exp. Neurol.

Brain Res. Bull.

Neuroscience

Anal. Biochem.

Eur. J. Pharmacol.

Neuroscience

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Brain Res.

J. Neurosci. Methods

Brain Res. Brain Res. Rev.

Biol. Psychiatry

Trends Neurosci.

J. Neurosci. Methods

Pharmacol. Biochem. Behav.

Brain Res. Brain Res. Rev.

Brain Res.

Brain Res.

Brain Res.

Eur. J. Pharmacol.

J. Neurosci. Methods

Brain Res.

Brain Res.

Pharmacol. Biochem. Behav.

Brain Res.