Increased Stimulated Release and Uptake of Dopamine in Nucleus Accumbens After Repeated Cocaine Administration as Measured by In Vivo Voltammetry

Ng, Jeffrey P.; Hubert, George W.; Justice, Joseph B.

doi:10.1111/j.1471-4159.1991.tb02042.x

Cited by 93 publications

(52 citation statements)

References 45 publications

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“…In one previous study, [DA] max was assessed in rats after a 10-day cocaine exposure and 24-h withdrawal. In that work, Ng et al (1991) used a prolonged length of stimulation (10 s) that led to a steady-state [DA] max response during stimulation with the goal of depleting the dopamine releasable pool. Importantly, they compared the maximal amount of dopamine available for release and observed a 44% [DA] max increase in cocaine-treated versus saline-treated subjects.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, we used FSCV to monitor electrically stimulated dopamine overflow in the NAc core and shell of anesthetized rats. This experimental design has been used extensively to characterize dopamine uptake and release under different conditions (Jones et al 1995;Mateo et al 2004;Ng et al 1991;Oleson et al 2008;Walker et al 2006;Wightman and Zimmerman 1990;Wu et al 2001a). Furthermore, this in vivo design is critical for kinetic analysis because the modeling of release and uptake used here cannot be performed without electrically stimulated dopamine overflow.…”

Section: Introductionmentioning

confidence: 99%

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Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

Addy¹,

Daberkow

Ford³

et al. 2010

Journal of Neurophysiology

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Addy NA, Daberkow DP, Ford JN, Garris PA, Wightman RM. Sensitization of rapid dopamine signaling in the nucleus accumbens core and shell after repeated cocaine in rats. J Neurophysiol 104: 922-931, 2010. First published June 16, 2010 doi:10.1152/jn.00413.2010. Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic voltammetry (FSCV) to determine whether repeated cocaine alters rapid dopamine release and uptake in the nucleus accumbens (NAc) core and shell. FSCV was performed in urethane anesthetized male Sprague-Dawley rats that had previously received one or seven daily injections of saline or cocaine (15 mg/kg, ip). In response to acute cocaine, subjects showed increased dopamine overflow that resulted from both increased dopamine release and slowed dopamine uptake. One-day cocaine preexposure, however, did not alter dopaminergic responses to a subsequent cocaine challenge. In contrast, 7-day cocaine-treated subjects showed a potentiated rapid dopamine response in both the core and shell after an acute cocaine challenge. In addition, kinetic analysis during the cocaine challenge showed a greater increase in apparent K m of 7-day cocaine exposed subjects. Together, the data provide the first in vivo demonstration of rapid dopamine sensitization in the NAc core and shell after a short withdrawal period. In addition, the data clearly delineate cocaine's release and uptake effects and suggest that the observed sensitization results from greater uptake inhibition in cocaine pre-exposed subjects. I N T R O D U C T I O NCocaine acts in the brain to slow dopamine uptake through inhibition of the dopamine transporter (DAT) (Ritz et al. 1987) and thus increases the amount of time that dopamine is present in the extraneuronal space. Cocaine's ability to increase dopamine overflow, particularly in the nucleus accumbens (NAc), has been shown to play an important role in several models of addiction (Goeders and Smith 1983;Kalivas and Duffy 1993a;Ritz et al. 1988;Rodd-Henricks et al. 2002). Specifically, dopaminergic mechanisms in the NAc shell have been shown to alter motivation for rewards such as cocaine, whereas dopamine in the NA core is important for goal-directed behavior (Ikemoto 2007; Ito et al. 2000 Ito et al. , 2004. In addition, repeated cocaine administration also leads to a progressive, or sensitized, increase of dopamine overflow (Heidbreder et al. 1996; Kalivas and Duffy 1993a,b) because of changes in the brain (Vanderschuren and Kalivas 2000;Wolf 1998). Specifically, cocaine has been shown to alter synaptic plasticity (Argilli et al. 2008; Borgland et al. 2004;Saal et al. 2003) and to modulate second messenger signaling proteins implicated in neuronal plasticity (Bibb e...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

Addy¹,

Daberkow

Ford³

et al. 2010

Journal of Neurophysiology

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“…This phenomenon, referred to as behavioral sensitization, persists for weeks after cessation of cocaine use and is implicated in the reinstatement of cocaine-seeking behavior (Kalivas and Duffy, 1993a;Henry and White, 1995;Shippenberg and Heidbreder, 1995). Behavioral sensitization is associated with an increase in firing rate of mesolimbic DA neurons (Henry et al, 1989), an elevation of basal DA dialysate levels (Kalivas and Duffy, 1993a,b;Heidbreder et al, 1996), and an increase in the basal rate of DA uptake (Ng et al, 1991;Parsons et al, 1991;Meiergerd et al, 1994;Jones et al, 1995). These adaptations in presynaptic DA activity are thought to contribute to the development and longterm expression of behavioral sensitization (Kalivas and Stewart, 1991).…”

Section: Abstract: -Opioid Receptors; Dopamine; Dopamine Uptake; Cocmentioning

confidence: 99%

κ-Opioid Receptor Activation Modifies Dopamine Uptake in the Nucleus Accumbens and Opposes the Effects of Cocaine

et al. 2000

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Coadministration of -opioid receptor agonists ( -agonists) with cocaine prevents alterations in dialysate dopamine (DA) concentration in the nucleus accumbens (Acb) that occur during abstinence from repeated cocaine treatment. Quantitative microdialysis was used to determine the mechanism producing these effects. Rats were injected with cocaine (20 mg/kg, i.p.), or saline, and the selective -agonist U-69593 (0.32 mg/kg, s.c.), or vehicle, once daily for 5 d. Extracellular DA concentration (DA ext ) and extraction fraction (E d ), an indirect measure of DA uptake, were determined 3 d later. Repeated cocaine treatment increased E d , whereas repeated U-69593 treatment decreased E d , relative to controls. Coadministration of both drugs yielded intermediate E d values not different from controls. In vitro DA uptake assays confirmed that repeated U-69593 treatment produces a doserelated, region-specific decrease in DA uptake and showed that acute U-69593 administration increases DA uptake in a norbinaltorphimine reversible manner. Repeated U-69593 also led to a decrease in [ 125 I]RTI-55 binding to the DA transporter (DAT), but did not decrease total DAT protein. These results demonstrate that -opioid receptor activation modulates DA uptake in the Acb in a manner opposite to that of cocaine: repeated U-69593 administration decreases the basal rate of DA uptake, and acute U-69593 administration transiently increases DA uptake. -agonist treatment also alters DAT function. The action of -agonists on DA uptake or DAT binding, or both, may be the mechanism(s) mediating the previously reported "cocaineantagonist" effect of -opioid receptor agonists.

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“…The mechanism for developmental changes in monoaminergic systems after prenatal cocaine exposure may be attributed to its ability to block neurotransmitter uptake in the fetal brain or the vasoconstrictor activity of the drug. Cocaine is known to inhibit high-affinity neurotransmitter uptake at the presynaptic nerve terminals in both adult animals and fetus brains (Pitts and Marwah, 1987;Meyer et al, 1994); therefore, cocaine enhances synaptic levels of dopamine, norepinephrine, and serotonin (Ng et al, 1991;Keller et al, 1994) following systemic and gestational administration. Cocaine has also been reported to reduce the fetal blood flow to decrease the supply of oxygen and other nutrients available to the fetus in the pregnant dams (Woods et al, 1987).…”

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confidence: 99%

Clozapine Protection against Gestational Cocaine-Induced Neurochemical Abnormalities

Yablonsky-Alter¹,

Gashi²,

Lidsky³

et al. 2004

J Pharmacol Exp Ther

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Clozapine was found to be effective in attenuating cocaine-induced neurochemical effects. We investigate whether clozapine influences in utero cocaine exposure-induced changes in striatal dopamine levels and cortical N-methyl-D-aspartate (NMDA) receptor density in mouse and rat brains. Pregnant mice or rats were injected with cocaine (5 or 10 mg/kg intraperitoneally) or saline every 24 h throughout gestation and continued for 6 weeks following the delivery. Striatal dopamine levels measured by highpressure liquid chromatography were found to decrease 24 to 33% in gestational cocaine exposed between the ages of 3 to 15 days, but not in 42-day-old pups. The cortical NMDA receptor densities assessed either in the presence of 100 M glutamate or 30 M glycine were significantly increased in 15-day-old gestational cocaine-exposed rats. Simultaneous daily administration of 3 mg/kg clozapine with 5 mg/kg cocaine to pregnant mice protected against the decrease in striatal dopamine levels or an increase in the concentration of NMDA receptor measured in the presence of 100 M glutamate in 15-day-old pups. Clozapine did not affect striatal dopamine levels by itself or when coadministered with cocaine in 42-day-old pups. The results show gestational cocaine may induce neurochemical abnormalities in brain exhibited as an increased glutamate NMDA receptor density together with a decreased striatal dopamine level. These effects of gestational cocaine exposure may be prevented by simultaneous administration of clozapine. Thus clozapine, which is a partial agonist at the NMDA receptor, may be of value in protecting against gestational cocaineinduced adverse effects in the brain.

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Increased Stimulated Release and Uptake of Dopamine in Nucleus Accumbens After Repeated Cocaine Administration as Measured by In Vivo Voltammetry

Cited by 93 publications

References 45 publications

Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

κ-Opioid Receptor Activation Modifies Dopamine Uptake in the Nucleus Accumbens and Opposes the Effects of Cocaine

Clozapine Protection against Gestational Cocaine-Induced Neurochemical Abnormalities

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