Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex

Bassareo, Valentina; Luca, Maria Antonietta De; Chiara, G. Di

doi:10.1007/s00213-006-0560-7

Cited by 64 publications

(62 citation statements)

References 60 publications

(63 reference statements)

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“…Although a specific role glutamate signaling in the shell vs. core in opiate seeking remains debatable, the shell-specific plasticity shown here is consistent with previous reports implicating a role for this region in opiate reward and relapse to drug seeking (19,(38)(39)(40)(41)(42)(43). It is worth noting, however, that reductions in NAc core A/N ratios due to up-regulation of NR2B-containing NMDAR currents have been reported following heroin self-administration in rats, and that this adaptation drives reinstatement of heroin seeking (24).…”

Section: Prefer Test Pre-testsupporting

confidence: 91%

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Hearing

Jedynak

Ebner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

142

169

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Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drugrelated behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type-specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10-14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortexaccumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies.opiates | nucleus accumbens | plasticity | GluA2-lacking AMPARs | ceftriaxone O pioid-based drugs are mainstays for pain management (1). However, side effects such as euphoria and the development of tolerance and dependence contribute to an increasing diversion of these readily available compounds for nontherapeutic use (2). Opioid agonist-based treatments are known to reduce some aspects of opioid addiction. On the other hand, these therapies often lead to high relapse rates when discontinued because they fail to eliminate key aspects of addiction such as conditioned associations that can trigger intense drug craving (2). Currently, development of alternative treatments for opioid addiction is hampered by a distinct lack of knowledge of the cellular plasticity that underlies persistent opioid-induced changes in behavior.The nucleus accumbens (NAc) region of the ventral striatum is involved in attribution of salience to drug-paired cues that can in turn motivate reward-related behavior (3, 4). Medium spiny neurons (MSNs), the principal cells of the NAc, are GABAergic projection neurons that receive coordinated glutamatergic afferents arising from several cortical and limbic brain regions (5, 6). MSNs are divided into two subpopulations based on expression of the dopamine receptor 1 (D1R-MSN) or dopamine receptor 2 (D2-MSN), with a small fraction (∼6-17%) expressing both receptors (7). Importantly, these subpopulations have divergent projection targets and exert antagonistic effects in rewardrelated behaviors (8).Long-lasting alterations in excitatory synaptic strength and glutamate release at MSNs produced by repeated exposure to drugs of abuse is a driving factor behind drug seeking and relapse (9-11). Numerous studies have examined effects of repeated psychostimulant exposure on synaptic strength and AMPA receptor (AMPAR)-mediated transmission in MSN subpopulations, with a majority of adaptati...

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Section: Prefer Test Pre-testsupporting

confidence: 91%

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Hearing

Jedynak

Ebner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

142

169

View full text Add to dashboard Cite

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“…This viewpoint is also supported by animal studies showing that MD but not CUPS induce severe anhedonia in rats (Bai, Zhang, et al., 2014). MD and CUPS also exert dissimilar effects on the expression of D1, D2‐like receptors, and DAT in some of the mesocorticolimbic dopaminergic pathways (Bassareo, De Luca, & Di Chiara, 2007; Brenes & Fornaguera, 2008). In this study, we first demonstrated that different depressive behaviors of rats such as anhedonia, passive coping behavior, and exploratory interest may be related to divergent dopaminergic pathways.…”

Section: Discussionmentioning

confidence: 99%

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

et al. 2017

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BackgroundThe mesocorticolimbic dopamine system, which originates from the ventral tegmental area (VTA) and projects primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy), plays a pivotal role in determining individual motivation and sensitivity to rewards, namely, anhedonia. Not all depressive individuals exhibited anhedonia, thus, it is natural to speculate that the heterogenous manifestations of depression might be related to the mesocorticolimbic dopamine system. Maternal deprivation (MD) and chronic unpredictable stress (CUPS) are two well‐established depressogenic stressors, and they were proven to induce different depressive phenotypes.MethodsThe depressive and anxiety‐like behaviors of MD and CUPS‐treated rats were measured by classical behavioral tests including open field, forced swimming, and sucrose preference test. The expression of D1‐5 dopamine receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system of rats exposed to MD and CUPS were measured by real‐time PCR and Western blot, respectively.ResultsSevere anhedonia was observed in MD but not CUPS rats. Divergent expression of D1 and D2 receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system were found between MD and CUPS rats. Significant correlations between different depressive behaviors and D1‐/D2‐like receptors and DAT protein levels in the mesocorticolimbic dopamine system were observed.ConclusionDifferent depressive behaviors of rats such as anhedonia, passive coping behavior, and declined exploratory interest might be related to divergent dopaminergic pathways. Anhedonia is associated with the dysfunction of VTA‐NAc and VTA‐OT dopaminergic pathways, the passive coping behavior is related to the dysregulation of VTA‐PFC and VTA‐AMy pathways, and individual exploratory interest is associated with abnormal activity of VTA‐PFC and VTA‐ST pathways.

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“…Interestingly, pharmacological manipulations of the NAc that increase affective oro-facial responses to the taste of sweet solutions are specific to the dorsal shell subregion, a so called 'hedonic hotspot' (Pecina and Berridge, 2005;Pecina et al, 2006). Further, the shell region appears to be involved in processing the primary reinforcing effects of drugs of abuse (Bassareo et al, 2007;Ito et al, 2004). Electrophysiological and pharmacological studies of this region have shown that, generally, increases in motivated behavior for a given stimulus appear to be driven by decreased activity in the NAc shell (Carlezon and Wise, 1996).…”

Section: Role Of Dopamine and Other Neurotransmitters In Reward And Amentioning

confidence: 99%

“…Furthermore, dopamine function in the core subregion of the NAc has been implicated in mediating the association of natural reward-related stimuli (Day et al, 2007;Parkinson et al, 2002) and the proper behavioral responses to stimuli that predict cocaine (Di Chiara et al, 2004;Ito et al, 2000;Ito et al, 2004). In contrast, the shell appears to be more responsive to the primary reinforcing or motivational properties of drugs and natural rewards (Di Chiara et al, 2004;Kelley et al, 2002;Kelley and Swanson, 1997;Pecina and Berridge, 2005); however see (Bassareo et al, 2007;Cheer et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Dissecting motivational circuitry to understand substance abuse

Wheeler

Carelli

2009

Neuropharmacology

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SummaryAn important goal of cocaine addiction research is to understand the neurobiological mechanisms underlying this disease state. Here, we review studies from our laboratory that examined nucleus accumbens (NAc) cell firing and rapid dopamine signaling using electrophysiological and electrochemical recordings in behaving rodents. A major advantage of these techniques is that they allow for the characterization of NAc activity and rapid dopamine release during specific phases of motivated behavior. Moreover, each approach enables an examination of the dynamic nature of NAc signaling as a function of factors such as hedonics and associative learning. We show that NAc neurons differentially respond to rewarding and aversive stimuli and their predictors in a bivalent manner. This differential responding is modifiable and can be altered by the presentation of other natural rewards or cocaine. Likewise, the dynamic nature of NAc cell firing is also reflected in the differential activation of distinct populations of NAc neurons during goal-directed behaviors for natural versus drug rewards, and the heightened activation of some NAc neurons following cocaine abstinence. Our electrochemical data also show that rapid dopamine signaling in the NAc reflects primary rewards and their predictors and appears to modulate specific NAc neuronal responses. In some cases, these influences are observed in a regionally specific manner that matches previous pharmacological manipulations. Collectively, these findings provide critical insight into the functional organization of the NAc that can be used to guide additional studies aimed at dissecting the neural code underlying compulsive drug-seeking behavior.

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Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex

Abstract: The results show that drug CSs stimulate DA release in the shell and medial PFCX and specifically potentiate the primary stimulant drug effects on DA transmission.

Cited by 64 publications

References 60 publications

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

Dissecting motivational circuitry to understand substance abuse

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