Dopamine and drug addiction: the nucleus accumbens shell connection

Chiara, G. Di; Bassareo, Valentina; Fenu, Sandro; Luca, Maria Antonietta De; Spina, Liliana; Cadoni, C; Acquas, Elio; Carboni, Ezio; Valentini, Valentina; Lecca, Daniele

doi:10.1016/j.neuropharm.2004.06.032

Cited by 787 publications

(639 citation statements)

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“…The DA response to a natural reward does not generally persist over time, as the organism rapidly habituates to these stimuli after a few exposures. Conversely, the response to addictive drugs is not influenced by habituation, as each drug administration stimulates the release of DA (Bradberry et al, 2000;Di Chiara et al, 2004;Lecca et al, 2007). In addition, the DA response of addictive substances is several fold higher than that elicited by novel, naturally occurring rewards .…”

Section: Mesostriatal Acetylcholine and Reward Mediationmentioning

confidence: 99%

“…This process forms the basis of drug-induced CPP and, relative to other types of conditioned learning, appears more difficult to extinguish. As there is an absence of habituation to drug-induced increases in DA (relative to natural rewards), the associations between the rewarding properties of cocaine and the related conditioned stimuli are continually strengthened with repeated use (Di Chiara et al, 2004). The NAc, amygdala, and basal forebrain all play a critical role in the development of conditioned learning following drug administration Everitt et al, 1999;Meil and See, 1997).…”

Section: Acetylcholine and Conditioned Learningmentioning

confidence: 99%

“…Dopamine (DA) has been identified as the critical neurotransmitter in the reward circuitry mediating substance abuse and the primary focus of preclinical research and clinical treatment interventions (Adinoff, 2004;Di Chiara et al, 2004;Self, 2004). DA levels abruptly increase following the administration of many drugs of abuse, including cocaine, and cocaine is no longer self-administered in animal models of addiction following DA receptor blockade within the nucleus accumbens (NAc) (Chang et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

157

138

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Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

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Section: Mesostriatal Acetylcholine and Reward Mediationmentioning

confidence: 99%

Section: Acetylcholine and Conditioned Learningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

157

138

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“…D-Amphetamine has been reported to ameliorate mood in patients suffering from depression (Maes et al, 1990), to enhance cognition in schizophrenics (Daniel et al, 1991), to ameliorate attention problems and impulsivity in attention deficit hyperactivity disorder (Lopez et al, 2004) and, when taken chronically, to lead to addiction (Di Chiara et al, 2004;White and Kalivas, 1998). In animals, Damphetamine produces hyperactivity, stereotypy, and extrapyramidal motor symptoms.…”

Section: Introductionmentioning

confidence: 99%

D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

Bhattacharjee

Chang

White

et al. 2006

J Cereb Blood Flow Metab

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In rat brain, dopaminergic D 2 -like but not D 1 -like receptors can be coupled to phospholipase A 2 (PLA 2 ) activation, to release the second messenger, arachidonic acid (AA, 20:4n-6), from membrane phospholipids. In this study, we hypothesized that D-amphetamine, a dopamine-releasing agent, could initiate such AA signaling. The incorporation coefficient, k* (brain radioactivity/integrated plasma radioactivity) for AA, a marker of the signal, was determined in 62 brain regions of unanesthetized rats that were administered i.p. saline, D-amphetamine (2.5 or 0.5 mg/kg i.p.), or the D 2 -like receptor antagonist raclopride (6 mg/kg, i.v.) before saline or 2.5 mg/kg D-amphetamine. After injecting [1-14 C]AA intravenously, k* was measured by quantitative autoradiography. Compared to saline-treated controls, D-amphetamine 2.5 mg/kg i.p. increased k* significantly in 27 brain areas rich in D 2 -like receptors. Significant increases were evident in neocortical, extrapyramidal, and limbic regions. Pretreatment with raclopride blocked the increments, but raclopride alone did not alter baseline values of k*. In independent experiments, D-amphetamine 0.5 mg/kg i.p. increased k* significantly in only seven regions, including the nucleus accumbens and layer IV neocortical regions. These results indicate that D-amphetamine can indirectly activate brain PLA 2 in the unanesthetized rat, and that activation is initiated entirely at D 2 -like receptors. D-Amphetamine's lowdose effects are consistent with other evidence that the nucleus accumbens, considered a reward center, is particularly sensitive to the drug.

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“…Cocaine is a monoamine reuptake inhibitor (Koe, 1976) and both the psychomotor-activating and rewarding properties of this stimulant are putatively mediated by an enhance- ment in monoamine neurotransmission within the NAC (eg, Vanderschuren and Kalivas, 2000;Di Chiara et al, 2004;Hall et al, 2004). Thus, in vivo microdialysis was conducted in the NAC to relate the protracted behavioral effects of pre-adolescent PPA administration to alterations in the dopamine, norepinephrine and serotonin responses to acute and repeated cocaine.…”

Section: Pre-adolescent Ppa Pretreatment Abolishes the Catecholamine mentioning

confidence: 99%

Protracted ‘Pro-Addictive’ Phenotype Produced in Mice by Pre-Adolescent Phenylpropanolamine

Szumlinski

Liu

Penzner

et al. 2007

Neuropsychopharmacol

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For decades, the sympathomimetic phenylpropanolamine (PPA; 7-norepinephrine) was an active ingredient found in popular children's over-the-counter (OTC) cold, cough, and allergy medications. To examine the possibility that pre-adolescent PPA exposure may induce neuroadaptations that influence behavioral and neurochemical responding to cocaine, C57BL/6J mice were pretreated with PPA (0-40 mg/kg) during postnatal days 21-31. The behavioral and neurochemical responses to acute and repeated cocaine (4 Â 15 mg/kg) were then assessed in adulthood when the mice were 10 weeks of age. Whereas pre-adolescent PPA exposure did not influence the acute locomotor response to 15 mg/kg cocaine, PPA pre-exposure dose-dependently enhanced the expression of cocaine-induced place conditioning, reduced the expression of locomotor sensitization, but did not influence cocaine-induced stereotypy. Pre-adolescent PPA exposure completely prevented the capacity of cocaine to elevate extracellular levels of catecholamines in the nucleus accumbens, but facilitated the development of cocaine-induced glutamate sensitization. Neither acute nor repeated cocaine altered extracellular GABA levels in the accumbens of control mice; however, 15 mg/kg cocaine lowered GABA levels by approximately 40% in PPA pretreated mice and this effect showed tolerance with repeated cocaine administration. These data provide the first evidence that early exposure to an OTC compound produces protracted effects upon cocaine-induced changes in nucleus accumbens neurotransmission that may contribute to a 'pro-addictive' phenotype in adulthood.

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Dopamine and drug addiction: the nucleus accumbens shell connection

Cited by 787 publications

References 94 publications

The Role of Acetylcholine in Cocaine Addiction

The Role of Acetylcholine in Cocaine Addiction

D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

Protracted ‘Pro-Addictive’ Phenotype Produced in Mice by Pre-Adolescent Phenylpropanolamine

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Dopamine and drug addiction: the nucleus accumbens shell connection

Cited by 787 publications

References 94 publications

The Role of Acetylcholine in Cocaine Addiction

The Role of Acetylcholine in Cocaine Addiction

D-Amphetamine Stimulates D2Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

Protracted ‘Pro-Addictive’ Phenotype Produced in Mice by Pre-Adolescent Phenylpropanolamine

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D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats