Dataset Information

Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists.

ABSTRACT: The conditioning of cocaine's subjective actions with environmental stimuli may be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of learning factors in persistent addictive behavior as well as the neurobiological basis of this phenomenon, rats were trained to associate discriminative stimuli (S(D)) with the availability of i.v. cocaine vs. nonrewarding saline solution, and then placed on extinction conditions during which the i.v. solutions and S(D)s were withheld. The effects of reexposure to the S(D) on the recovery of responding at the previously cocaine-paired lever and on Fos protein expression then were determined in two groups. One group was tested immediately after extinction, whereas rats in the second group were confined to their home cages for an additional 4 months before testing. In both groups, the cocaine S(D), but not the non-reward S(D), elicited strong recovery of responding and increased Fos immunoreactivity in the basolateral amygdala and medial prefrontal cortex (areas Cg1/Cg3). The response reinstatement and Fos expression induced by the cocaine S(D) were both reversed by selective dopamine D(1) receptor antagonists. The undiminished efficacy of the cocaine S(D) to elicit drug-seeking behavior after 4 months of abstinence parallels the long-lasting nature of conditioned cue reactivity and cue-induced cocaine craving in humans, and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. Moreover, the results implicate D(1)-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala as substrates for cocaine-seeking behavior elicited by cocaine-predictive environmental stimuli.

SUBMITTER: Ciccocioppo R

PROVIDER: S-EPMC29367 | biostudies-literature | 2001 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists.

Ciccocioppo R R Sanna P P PP Weiss F F

Proceedings of the National Academy of Sciences of the United States of America 20010201 4

The conditioning of cocaine's subjective actions with environmental stimuli may be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of learning factors in persistent addictive behavior as well as the neurobiological basis of this phenomenon, rats were trained to associate discriminative stimuli (S(D)) with the availability of i.v. cocaine vs. nonrewarding saline solution, and then placed on extinction conditions during which the i.v. sol ...[more]

PMID: 11172061

Similar Datasets

Project description:Chronic cocaine exposure influences the density and morphology of dendritic spines on medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a critical brain region for cocaine craving. However, the relationship between spine plasticity and craving remains unclear. To study this relationship, we trained rats to self-administer cocaine using an extended-access regimen (6 h per day, 10 days); controls self-administered saline. Previously, a time-dependent intensification (incubation) of cue-induced cocaine craving has been demonstrated after withdrawal from this regimen; furthermore, Ca2+-permeable AMPA receptors (CP-AMPARs) increase in the NAc core after ~1 month of withdrawal and thereafter mediate the expression of incubated craving. Although neither craving nor CP-AMPAR levels were measured in the present study, we killed rats at four withdrawal day (WD) time-points (WD14, WD25, WD36, or WD60) selected to span the rising phase of incubation and the transition from low to high CP-AMPAR levels. MSNs were iontophoretically filled with Lucifer yellow and spines were analyzed with NeuronStudio software. Compared with saline controls, cocaine rats showed no changes in spine density or morphology in the NAc core on WD14 or WD25. On WD36, approximately the withdrawal time when stable elevation of CP-AMPAR levels is detected, the cocaine group exhibited increased density of thin spines in the NAc core. By WD60, however, this effect had reversed: the density of thin spines was lower in cocaine rats compared with saline rats. In contrast, craving and CP-AMPAR levels remain high on WD60. We also assessed spine density on WD36 in the dorsolateral striatum, a region that is not implicated in incubation of cocaine craving and does not undergo CP-AMPAR plasticity. Here, the cocaine group exhibited a small leftward shift in the distribution of spine densities plotted as a cumulative distribution, opposite to the effect found in the NAc core. Overall, our results demonstrate changes in NAc core spines over 2 months of withdrawal but no simple relationship between the time dependency of these spine changes and the previously demonstrated time course of incubation of cocaine craving. However, they raise the possibility that CP-AMPAR accumulation in the NAc core occurs in a population of thin spines that emerges after ~1 month of withdrawal.

Dataset Information

Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists.

Publications

Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets