c-Fos and ΔFosB expression are differentially altered in distinct subregions of the nucleus accumbens shell in cocaine-sensitized rats

Brenhouse, Heather C.; Stellar, James R.

doi:10.1016/j.neuroscience.2005.09.039

Cited by 50 publications

(41 citation statements)

References 40 publications

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“…Conversely, repeated cocaine exposure and place conditioning provoked potent effects on earlygene expression in the core and shell sectors of the N Acc and DMst. It is noteworthy that acute cocaine treatment did not elevate c-Fos levels in the shell sector of the N acc, but the early-gene response did sensitize with repeated exposure, as earlier shown in rats (Brenhouse and Stellar, 2006). A novel finding of these experiments was that pretreatment with the BZT analog blocked cocaine-stimulated CPP.…”

Section: Discussionsupporting

confidence: 66%

The Dopamine Uptake Inhibitor 3α-[bis(4′-fluorophenyl)metoxy]-tropane Reduces Cocaine-Induced Early-Gene Expression, Locomotor Activity, and Conditioned Reward

Velázquez-Sánchez

Ferragud

Hernández‐Rabaza

et al. 2009

Neuropsychopharmacol

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Benztropine (BZT) analogs, a family of high-affinity dopamine transporter ligands, are molecules that exhibit pharmacological and behavioral characteristics predictive of significant therapeutic potential in cocaine addiction. Here, we examined in mice the effects of 3a-[bis(4 0 -fluorophenyl)metoxy]-tropane (AHN-1055) on motor activity, conditioned place preference (CPP) and c-Fos expression in the striatum. AHN-1055 produced mild attenuation of spontaneous locomotor activity at a low dose (1 mg/kg) and weak stimulation at a higher dose (10 mg/kg). In parallel, the BZT analog significantly increased c-Fos expression in the dorsolateral caudoputamen at the high dose, whereas producing marginal decreases at low and moderate doses (1, 3 mg/kg) in both dorsal and ventral striatum. Interaction assays showed that cocaine's ability to stimulate locomotor activity was decreased by AHN-1055 treatment, but not by treatment with D-amphetamine. Such reduced ability did not result from an increase in stereotyped behavior. Another dopamine uptake inhibitor, nomifensine, decreased cocaine-induced locomotor activity but evoked by itself intense motor stereotypies. Remarkably, the BZT analog dose-dependently blocked cocaine-induced CPP without producing CPP when given alone, and blocked in conditioned mice cocainestimulated early-gene activation in the nucleus accumbens and dorsomedial striatum. These observations provide evidence that AHN-1055 does not behave as a classical psychomotor stimulant and that some of its properties, including attenuation of cocaine-induced striatal c-Fos expression, locomotor stimulation, and CPP, support its candidacy, and that of structurally related molecules, as possible pharmacotherapies in cocaine addiction.

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Section: Discussionsupporting

confidence: 66%

The Dopamine Uptake Inhibitor 3α-[bis(4′-fluorophenyl)metoxy]-tropane Reduces Cocaine-Induced Early-Gene Expression, Locomotor Activity, and Conditioned Reward

Velázquez-Sánchez

Ferragud

Hernández‐Rabaza

et al. 2009

Neuropsychopharmacol

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“…Moreover, subterritorial differences in cocaine-induced neuroadaptations have been observed in previous studies (eg Sorg et al, 1995;Robinson et al, 2001;Thomas et al, 2001;Ricci et al, 2004;Brenhouse and Stellar, 2006). The different magnitude of change in firing between core and shell in the present study might thus correspond to a subterritorial difference in the types of neuroadaptations that are induced by cocaine.…”

Section: Core Vs Shellsupporting

confidence: 74%

“…Cocaine addiction is defined by an increase in drug-directed behavior and a concomitant weakening of other motivated behaviors (American Psychiatric Association, 1994). Although the accumbens and interconnected structures facilitate drugdirected behavior, they also facilitate multiple alternative motivated behaviors (eg Everitt, 1990;Blackburn et al, 1992;Ikemoto and Panksepp, 1999;Cardinal et al, 2002;Kelley, 2004;Schwienbacher et al, 2004;Wise, 2004;Salamone et al, 2005). Given the selective changes in behavior that define addiction, it is difficult to envision how a general hypoactivity of the accumbens and interconnected circuits could contribute to drug addiction.…”

Section: Introductionmentioning

confidence: 99%

Accumbal Neurons that are Activated during Cocaine Self-Administration are Spared from Inhibitory Effects of Repeated Cocaine Self-Administration

Peoples

Kravitz

Lynch

et al. 2006

Neuropsychopharmacol

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Hypoactivity of the accumbens is induced by repeated cocaine exposure and is hypothesized to play a role in cocaine addiction. However, it is difficult to understand how a general hypoactivity of the accumbens, which facilitates multiple types of motivated behaviors, could contribute to the selective increase in drug-directed behavior that defines addiction. Electrophysiological recordings, made during sessions in which rats self-administer cocaine, show that most accumbal neurons that encode events related to drugdirected behavior achieve and maintain higher firing rates during the period of cocaine exposure (Task-Activated neurons) than do other accumbal neurons (Task-Non-Activated neurons). We have hypothesized that this difference in activity makes the neurons that facilitate drug-directed behavior less susceptible than other neurons to the chronic inhibitory effects of cocaine. A sparing of neurons that facilitate drug-directed behavior from chronic hypoactivity might lead to a relative increase in the transmission of neuronal signals that facilitate drug-directed behavior through accumbal circuits and thereby contribute to changes in behavior that characterize addiction (ie differential inhibition hypothesis). A prediction of the hypothesis is that neurons that are activated in relation to task events during cocaine self-administration sessions will show less of a decrease in firing across repeated self-administration sessions than will other neurons. To test this prediction, rats were exposed to 30 daily (6 h/day) cocaine self-administration sessions. Chronic extracellular recordings of single accumbal neurons were made during the second to third session and the 30th session. Between-session comparisons showed that decreases in firing were exhibited by Task-Non-Activated, but not by Task-Activated, neurons. During the day 30 session, the magnitude of the difference in firing rate between the two groups of neurons was positively related to the propensity of animals to seek and take cocaine. The findings of the present study are consistent with a basic prediction of the differential inhibition hypothesis and may be relevant to understanding cocaine addiction.

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“…Stimulation of dopamine transmission by psychostimulants induces dose-dependent expression of c-Fos in rat striatum (Brenhouse and Stellar, 2006;Graybiel et al, 1990). This effect is abolished by pretreatment with the D1R antagonist SHC 23390, (Graybiel et al, 1990) and is lost in D1 KO mice (Moratalla et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell

et al. 2015

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Microdialysis during i.v. drug self-administration (SA) have implicated nucleus accumbens (NAc) shell DA in cocaine and heroin reinforcement. However, this correlative evidence has not been yet substantiated by experimental evidence obtained by studying the effect of selective manipulation of NAc shell DA transmission on cocaine and heroin SA. In order to investigate this issue, DA D1a receptor (D1aR) expression was impaired in the NAc shell and core by locally infusing lentiviral vectors (LV) expressing specific D1aR-siRNAs (LV-siRNAs). Control rats were infused in the same areas with LV expressing GFP. Fifteen days later, rats were trained to acquire i.v. cocaine or heroin self-administration (SA). At the end of behavioral experiments, in order to evaluate the effect of LV-siRNA on D1aR expression, rats were challenged with amphetamine and the brains were processed for immunohistochemical detection of cFos and D1aR. Control rats acquired i.v. cocaine and heroin SA. Infusion of LV-siRNAs in the medial NAc shell reduced D1aR density and the number of c-Fos positive nuclei in the NAc shell, while sparing the core, and prevented the acquisition of cocaine, but not heroin SA. In turn, LV-siRNAs infusion in the core reduced D1aR density and the number of c-Fos positive nuclei in the same area, while sparing the shell, and failed to affect acquisition of cocaine. The differential effect of LV impairment of NAc shell D1aR on cocaine and heroin SA indicates that NAc shell DA acting on D1aR specifically mediates cocaine reinforcement.

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c-Fos and ΔFosB expression are differentially altered in distinct subregions of the nucleus accumbens shell in cocaine-sensitized rats

Cited by 50 publications

References 40 publications

The Dopamine Uptake Inhibitor 3α-[bis(4′-fluorophenyl)metoxy]-tropane Reduces Cocaine-Induced Early-Gene Expression, Locomotor Activity, and Conditioned Reward

The Dopamine Uptake Inhibitor 3α-[bis(4′-fluorophenyl)metoxy]-tropane Reduces Cocaine-Induced Early-Gene Expression, Locomotor Activity, and Conditioned Reward

Accumbal Neurons that are Activated during Cocaine Self-Administration are Spared from Inhibitory Effects of Repeated Cocaine Self-Administration

Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell

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