Cocaine-Induced Plasticity of Intrinsic Membrane Properties in Prefrontal Cortex Pyramidal Neurons: Adaptations in Potassium Currents

Dong, Yan; Nasif, Fernando J.; Tsui, Jennifer; Ju, William; Cooper, Donald; Hu, Xiu‐Ti; Malenka, Robert C.; White, Francis J.

doi:10.1523/jneurosci.4715-04.2005

Cited by 113 publications

(101 citation statements)

References 28 publications

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“…In fact, in these rats, PFC neurons showed increased burst strength in response to cocaine. It has been demonstrated that repeated exposure to cocaine decreases inwardly rectifying K ϩ currents and increases voltage-sensitive Ca 2ϩ currents in response to depolarizing stimuli (Dong et al, 2005;Nasif et al, 2005). These changes could contribute to enhanced responsiveness of PFC neurons to psychostimulants.…”

Section: Discussionmentioning

confidence: 99%

“…These changes could contribute to enhanced responsiveness of PFC neurons to psychostimulants. One potential mechanism underlying the effects of cocaine on K ϩ channels involves the cAMP/protein kinase A (PKA) pathway (Dong et al, 2005). PKA can phosphorylate K ϩ channels and consequently decrease K ϩ currents (Dong and White, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…PKA can phosphorylate K ϩ channels and consequently decrease K ϩ currents (Dong and White, 2003). Repeated exposure to cocaine upregulates the cAMP/PKA pathway in PFC neurons (Dong et al, 2005 (Stoof and Kebabian, 1981). Because cocaine increases extracellular DA levels by blocking DA uptake, it may either increase or decrease PKA activity depending on which receptor subtype is predominantly activated.…”

Section: Discussionmentioning

confidence: 99%

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Repeated Cocaine Self-Administration Alters Processing of Cocaine-Related Information in Rat Prefrontal Cortex

2006

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One of the core symptoms of cocaine addiction is compulsive drug-seeking behavior. Although the precise neural substrates are unknown, it has been hypothesized that this behavior involves cocaine-induced hypofunction of the prefrontal cortex (PFC) or "hypofrontality." To test this hypothesis, PFC neuronal activity was monitored in rats during ϳ3 weeks of cocaine self-administration (SA). Rats were trained to press a lever to self-administer cocaine in daily 2 h sessions. Responding was reinforced contingent on a modified fixed-ratio 5 schedule of reinforcement. In the first SA session, the overall firing rate and burst rate were significantly decreased after cocaine infusions relative to the period immediately before the session. These effects disappeared after Ն10 d of drug SA and were replaced by a significant increase in burst duration and firing rate within a burst. Notably, however, the level of basal activity before the first drug infusion of each SA session decreased significantly after multiple weeks of cocaine exposure. Collectively, these data support the view that although repeated sessions of cocaine SA decrease basal PFC activity, increased burst-related firing in response to cocaine infusions suggests that processing of cocaine-related information is enhanced and may contribute to increased control by cocaine over cocaine-seeking behavior.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Repeated Cocaine Self-Administration Alters Processing of Cocaine-Related Information in Rat Prefrontal Cortex

2006

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“…As clinical imaging studies have provided increasing evidence for abnormal pattern of PFC activation in individuals addicted to psychostimulants (Volkow et al, 1992;Grant et al, 1996;London et al, 2000;Bolla et al, 2003;Ersche et al, 2005), rodent studies have followed suit and have reported psychostimulant-induced sustained changes in the pattern of dendritic morphology, membrane excitability, and gene expression (Lu et al, 1997;Sorg et al, 1997;Crombag et al, 2004;Robinson and Kolb, 2004;Dong et al, 2005). In response to the first exposure to amphetamine, we have observed a profound effect on spontaneous activity of neurons in both the mPFC and OFC (Homayoun and Moghaddam, 2006).…”

Section: Neuroplasticity Of Pfc Circuitry In An Animal Modelmentioning

confidence: 99%

Divergent Plasticity of Prefrontal Cortex Networks

Moghaddam

Homayoun

2007

Neuropsychopharmacol

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The 'executive' regions of the prefrontal cortex (PFC) such as the dorsolateral PFC (dlPFC) and its rodent equivalent medial PFC (mPFC) are thought to respond in concert with the 'limbic' regions of the PFC such as the orbitofrontal (OFC) cortex to orchestrate behavior that is consistent with context and expected outcome. Both groups of regions have been implicated in behavioral abnormalities associated with addiction and psychiatric disorders, in particular, schizophrenia and mood disorders. Theories about the pathophysiology of these disorders, however, incorporate abnormalities in discrete PFC regions independently of each other or assume they are one and the same and, thus, bunch them under umbrella of 'PFC dysfunction.' Emerging data from animal studies suggest that mPFC and OFC neurons display opposing patterns of plasticity during associative learning and in response to repeated exposure to psychostimulants. These data corroborate clinical studies reporting different patterns of activation in OFC versus dlPFC in individuals with schizophrenia or addictive disorders. These suggest that concomitant but divergent engagement of discrete PFC regions is critical for learning stimulus-outcome associations, and the execution of goal-directed behavior that is based on these associations. An atypical interplay between these regions may lead to abnormally high or low salience assigned to stimuli, resulting in symptoms that are fundamental to many psychiatric and addictive disorders, including attentional deficits, improper affective response to stimuli, and inflexible or impulsive behavior.

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“…These results suggest that, besides affecting responsivity to D 2 receptor antagonists, cocaine treatment is affecting intrinsic currents in cortical cells. Arguing against this possibility, recent studies in dissociated PFC pyramidal cells after withdrawal from cocaine demonstrate increased excitability as a result of a decreased voltage-gated and inwardly rectifying I k and enhanced L-type I Ca2ϩ (Dong et al, 2005;Nasif et al, 2005a). Moreover, Nasif et al (2005b) showed that repeated cocaine administration increased the membrane excitability of PFC neurons in slices.…”

Section: Repeated Treatment With Cocaine Depresses Evoked Cortical Exmentioning

confidence: 99%

Long-Term Neuroadaptations Produced by Withdrawal from Repeated Cocaine Treatment: Role of Dopaminergic Receptors in Modulating Cortical Excitability

Nogueira¹,

Kalivas²,

Lavín³

2006

J. Neurosci.

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Dopamine (DA) modulates neuronal activity in the prefrontal cortex (PFC) and is necessary for optimal cognitive function. Dopamine transmission in the PFC is also important for the behavioral adaptations produced by repeated exposure to cocaine. Therefore, we investigated the effects of repeated cocaine treatment followed by withdrawal (2-4 weeks) on the responsivity of cortical cells to electrical stimulation of the ventral tegmental area (VTA) and to systemic administration of DA D 1 or D 2 receptor antagonists. Cortical cells in cocaine-and saline-treated animals exhibited a similar decrease in excitability after the administration of D 1 receptor antagonists. In contrast, cortical neurons from cocaine-treated rats exhibited a lack of D 2 -mediated regulation relative to saline rats. Furthermore, in contrast to saline-treated animals, VTA stimulation did not increase cortical excitability in the cocaine group. These data suggest that withdrawal from repeated cocaine administration elicits some long-term neuroadaptations in the PFC, including (1) reduced D 2 -mediated regulation of cortical excitability, (2) reduced responsivity of cortical cells to phasic increases in DA, and (3) a trend toward an overall decrease in excitability of PFC neurons.

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Cocaine-Induced Plasticity of Intrinsic Membrane Properties in Prefrontal Cortex Pyramidal Neurons: Adaptations in Potassium Currents

Cited by 113 publications

References 28 publications

Repeated Cocaine Self-Administration Alters Processing of Cocaine-Related Information in Rat Prefrontal Cortex

Repeated Cocaine Self-Administration Alters Processing of Cocaine-Related Information in Rat Prefrontal Cortex

Divergent Plasticity of Prefrontal Cortex Networks

Long-Term Neuroadaptations Produced by Withdrawal from Repeated Cocaine Treatment: Role of Dopaminergic Receptors in Modulating Cortical Excitability

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