Escalation of cocaine self‐administration does not depend on altered cocaine‐induced nucleus accumbens dopamine levels

  title={Escalation of cocaine self‐administration does not depend on altered cocaine‐induced nucleus accumbens dopamine levels},
  author={Serge H. Ahmed and Daniel Lin and George F. Koob and Loren H. Parsons},
  journal={Journal of Neurochemistry},
Previous studies showed that prolonged access to cocaine or heroin self‐administration (long access, or LgA) produces an escalation in drug intake not observed with limited access to the drug (short access, or ShA). The present experiment employed in vivo microdialysis to test the role of alterations in drug pharmacokinetics and/or efficacy in increasing dopamine (DA) levels in the nucleus accumbens (NAcc) during cocaine intake escalation. In experiment 1, both ShA and LgA rats were challenged… 
Extended access of cocaine self‐administration results in tolerance to the dopamine‐elevating and locomotor‐stimulating effects of cocaine
Both neurochemical and behavioral cocaine tolerance is demonstrated in an extended‐access rodent model of cocaine abuse, which allows for a better understanding of the neuro chemical and psychomotor tolerance that develops to cocaine in human addicts.
Changes in response to a dopamine receptor antagonist in rats with escalating cocaine intake
Data support the hypothesis that alterations in dopamine neurotransmission contribute to escalation of cocaine self-administration and shift the biphasic dose–effect function to the left in LgA rats relative to ShA rats, thereby decreasing the threshold dose at which behavior was completely suppressed.
Incentive and dopamine sensitization produced by intermittent but not long access cocaine self‐administration
IntA experience was more effective than LgA in producing addiction‐like behavior—a drug experience‐dependent increase in motivation for cocaine assessed using behavioral economic procedures, and cue‐induced reinstatement—despite much less total drug consumption.
Withdrawal from extended‐access cocaine self‐administration results in dysregulated functional activity and altered locomotor activity in rats
It is demonstrated that behavioral and neurochemical impairments following cocaine self‐administration are present in the absence of drug and persist after cocaine has cleared, a time point when behavioral changes are present.
Dopamine Uptake Changes Associated with Cocaine Self-Administration
The data demonstrate that cocaine-induced dopamine transporter (DAT) inhibition accounts for the accumbal dopamine fluctuations, which are associated with the cyclic regularity of cocaine intake observed during self-administration.
Continuous exposure to dizocilpine facilitates escalation of cocaine consumption in male Sprague-Dawley rats.
  • R. Allen
  • Psychology, Biology
    Drug and alcohol dependence
  • 2014
Temporal Pattern of Cocaine Intake Determines Tolerance vs Sensitization of Cocaine Effects at the Dopamine Transporter
Assessment of voltammetry in the nucleus accumbens slices following control, IntA, ShA, and LgA self-administration found tolerance seems to be produced by high intake, while sensitization is produced by intermittent temporal patterns of intake.
Effects of cocaine self-administration history under limited and extended access conditions on in vivo striatal dopamine neurochemistry and acoustic startle in rhesus monkeys
Evidence is provided of a hypofunctional dopamine system that is not associated with an escalation in drug intake or reflected in measures of acoustic startle, and there was no effect of drug-taking history on sensitivity to psychostimulant-induced enhancement of startle amplitude.
Acquisition of and withdrawal from cocaine self‐administration regulates 5‐HT1B mRNA expression in rat striatum
The results suggest that the influence of 5‐HT1B receptors in striatal projection neurons may be increased during cocaine acquisition and reduced after forced abstinence and may therefore be targets for pharmacological intervention in addiction.
Binge self-administration and deprivation produces sensitization to the reinforcing effects of cocaine in rats
These data suggest that these self-administration-induced changes in breakpoint reflect sensitization, and show that a drug-free deprivation period is necessary, but not sufficient, to produce this increase.


Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after unlimited access to intravenous cocaine.
The results suggest that deficient 5-HT neurotransmission may be a significant factor in the cocaine withdrawal symptomatology and provide key information regarding nondopaminergic mechanisms involved in cocaine dependence.
Dopamine release during cocaine self-administration in rats: effect of SCH23390
Long-lasting increase in the set point for cocaine self-administration after escalation in rats
Data suggest that the transition to escalated levels of intake is associated with a long-lasting change in cocaine set point, and LgA rats took nearly two times as much cocaine than ShA rats.
Differences in extracellular dopamine concentrations in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat
NAcc [DA]e was significantly increased when the delivery of cocaine infusions was contingent on the behavior of the rat, indicative of a role in the neural processes underlying cocaine reinforcement.
In vivo Amygdala Dopamine Levels Modulate Cocaine Self‐administration Behaviour in the Rat: D1 Dopamine Receptor Involvement
A significant contribution of in vivo amygdala D1 dopamine transmission to cocaine self‐administration behaviour is found and nucleus accumbens dopamine levels are modified.
Effect of cocaine self‐administration on striatal dopamine D1 receptors in rhesus monkeys
It is suggested that chronic self‐administration of cocaine can modulate the density of dopamine D1 receptors in specific portions of the primate striatum.
Comparison of changes in extracellular dopamine concentrations in the nucleus accumbens during intravenous self‐administration of cocaine or d‐amphetamine
The results confirm that self-administration of cocaine or d-amphetamine by the rat is accompanied by a significant increase in extracellular DA concentrations in the nucleus accumbens, and adds credence to the hypothesis that their reinforcing properties are related to dynamic changes in DA concentration in the ventral striatal region of the brain.
Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats
Monitoring of dopamine and DOPAC levels in nucleus accumbens septi was consistent with the hypothesis that falling dopamine levels trigger successive responses in the intravenous cocaine self-administration paradigm, but inconsistent with the notion that extracellular dopamine levels are depleted at the times within sessions when the animal initiate drug-seeking responses.