Paradoxical Abatement of Striatal Dopaminergic Transmission by Cocaine and Methylphenidate

Federici, Mauro; Latagliata, Emanuele Claudio; Ledonne, Ada; Rizzo, Francesca Romana; Feligioni, Marco; Sulzer, Dave; Dunn, Matthew R.; Sameš, Dalibor; Gu, Howard H.; Nisticò, Robert; Puglisi-Allegra, Stefano; Mercuri, Nicola Biagio

doi:10.1074/jbc.m113.495499

Cited by 28 publications

(21 citation statements)

References 38 publications

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“…8D). Previous research has demonstrated that the effects of cocaine on DA uptake and release are mediated through independent mechanisms (Federici et al, 2014; Venton et al, 2006). Consequently, we verified that changes in cocaine’s effect on DA uptake and release were altered independently by analyzing the relationship between cocaine-induced DA uptake inhibition ( K i ) and DA release (Calipari et al, 2015).…”

Section: 0 Resultsmentioning

confidence: 99%

Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine

et al. 2017

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Patients with post-traumatic stress disorder have a heightened vulnerability to developing substance use disorders; however, the biological underpinnings of this vulnerability remain unresolved. We used the predator odor stress model of post-traumatic stress disorder with segregation of subjects as susceptible or resilient based on elevated plus maze behavior and context avoidance. We then determined behavioral and neurochemical differences across susceptible, resilient, and control populations using a panel of behavioral and neurochemical assays. Susceptible subjects showed a significant increase in the motoric and dopaminergic effects of cocaine, and this corresponded with heightened motivation to self-administer cocaine. Resilient subjects did not show differences in the motoric effects of cocaine, in dopamine signaling vivo, or in any measure of cocaine self-administration. Nonetheless, we found that these animals displayed elevations in both the dopamine release-promoting effects of cocaine and dopamine autoreceptor sensitivity ex vivo. Our results suggest that the experience of traumatic stress may produce alterations in dopamine systems that drive elevations in cocaine self-administration behavior in susceptible subjects, but may also produce both active and passive forms of resilience that function to prevent gross changes in cocaine’s reinforcing efficacy in resilient subjects.

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Section: 0 Resultsmentioning

confidence: 99%

Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine

et al. 2017

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“…However, the current work provides initial evidence for a possible mechanism by which cocaine reinforcement is increased in SI animals, specifically the differences observed in NAc dopamine release across all cocaine concentrations. In addition to cocaine’s direct effects on DAT-mediated uptake, there are also many other direct and indirect effects that may influence dopamine transmission, including increased D2 autoreceptor activity (Gantz et al, 2013), voltage gated Na+ channel blockade (Wang, 1988), synapsin dependent dopamine pool mobilization (Venton et al, 2006; Kile et al, 2010; Federici et al, 2014) and heterosynaptic activity from feedback circuits to name a few (Zhang and Sulzer, 2012; Ferris et al, 2013). Considering these many effects of cocaine, it is difficult to know what differences between SI and GH rats may be driving greater cocaine-induced release in the NAc of SI rats.…”

Section: Discussionmentioning

confidence: 99%

Social isolation rearing increases dopamine uptake and psychostimulant potency in the striatum

et al. 2016

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Social isolation rearing (SI) is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like behaviors. These animals also exhibit an increased propensity to administer psychostimulants, such as cocaine; however, the mechanisms governing this increased addiction vulnerability remains to be elucidated. Long-term stressors have been shown to produce important alterations in nucleus accumbens core (NAc) function. The NAc regulates motivated and goal-directed behaviors, and individual differences in NAc function have been shown to be predictive of addiction vulnerability. Rats were reared in group (GH; 4/cage) or SI (1/cage) conditions from weaning (PD 28) into early adulthood (PD 77) and dopamine release was assessed using voltammetry in brain slices containing the NAc and dorsomedial striatum. SI rats exhibited enhanced dopamine release and uptake in both regions compared to GH rats. In regard to psychostimulant effects directly at the dopamine transporter (DAT), methylphenidate and amphetamine, but not cocaine, inhibited uptake more in SI than GH rats. The increased potencies were positively correlated with uptake rates, suggesting that increased potencies of amphetamine-like compounds are due to changes in DAT function. Cocaine’s effects on uptake were similar between rearing conditions, however, cocaine enhanced evoked dopamine release greater in SI than GH rats, suggesting that the enhanced cocaine reinforcement in SI animals involves a DAT independent mechanism. Together, the results provide the first evidence that greater psychostimulant effects in SI compared to GH rats are due to effects on dopamine terminals related to uptake dependent and independent mechanisms.

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“…Indeed, DAT inhibition by cocaine in PC12 cells causes a concentration-dependent decrease DA released per quantal event [379]. Evoked striatal DA release can also be decreased by sufficiently high concentrations of cocaine and methylphenidate [380]. In PC12 cells, this is not due to an inhibitory effect of D2 autoreceptor activation on quantal size from elevated [DA] o , as the effect of cocaine is unaltered by sulpiride, a D2-receptor antagonist [381].…”

Section: Dopamine Uptakementioning

confidence: 99%

Striatal dopamine neurotransmission: Regulation of release and uptake

2016

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Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and the somatodendritic compartment in midbrain, and by clearance by the DA transporter, diffusion, and extracellular metabolism. We review how axonal DA release is regulated by neuronal activity and by autoreceptors and heteroreceptors, and address how quantal release events are regulated in size and frequency. In brain regions densely innervated by DA axons, DA clearance is due predominantly to uptake by the DA transporter, whereas in cortex, midbrain, and other regions with relatively sparse DA inputs, the norepinephrine transporter and diffusion are involved. We discuss the role of DA uptake in restricting the sphere of influence of DA and in temporal accumulation of extracellular DA levels upon successive action potentials. The tonic discharge activity of DA neurons may be translated into a tonic extracellular DA level, whereas their bursting activity can generate discrete extracellular DA transients.

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Paradoxical Abatement of Striatal Dopaminergic Transmission by Cocaine and Methylphenidate

Cited by 28 publications

References 38 publications

Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine

Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine

Social isolation rearing increases dopamine uptake and psychostimulant potency in the striatum

Striatal dopamine neurotransmission: Regulation of release and uptake

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