Destruction of dopaminergic nerve terminals in nucleus accumbens: Effect on d-amphetamine self-administration

Lyness, William H.; Friedle, N.M.; Moore, Kenneth E.

doi:10.1016/0091-3057(79)90040-6

Cited by 438 publications

(129 citation statements)

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“…Studies into the role of the nucleus accumbens in addictive behavior date back to the 1970s (Roberts et al, 1977;Glick and Cox, 1978;Lyness et al, 1979). On the basis of the pioneering studies by Di Chiara and colleagues in the 1980s that showed that different drugs abused by humans all increase dopamine release within the nucleus accumbens (Di Chiara and Imperato, 1988), numerous pharmacological and molecular studies have substantiated the involvement of the ventral striatum in self-administration of different classes of abused drugs (Ikemoto and Wise, 2004;Pierce and Kumaresan, 2006).…”

Section: Neurobiological Mechanisms Of Compulsive Drug Use Ventral Anmentioning

confidence: 99%

Compulsive drug use and its neural substrates

Lesscher

Vanderschuren²

2012

Reviews in the Neurosciences

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Drug addiction is a chronic relapsing brain disease, characterized by compulsive drug use. Despite the fact that drug addiction affects millions of people worldwide, treatments for this disorder are limited in number and efficacy. In our opinion, understanding the neural underpinnings of drug addiction would open new avenues for the development of innovative treatments for this disorder. Based on an awareness that drug use and drug reward do not equal drug addiction, there has been increasing interest in developing animal models of addiction that mimick the loss of control over drug use more closely than existing models aimed at studying drug reward. The present review provides an overview of animal studies of compulsive drug use and the neural mechanisms involved. First, the employed models are summarized, with a particular emphasis on models of escalation of drug use and resistance to punishment. Next, we discuss mechanisms within the (ventral and dorsal) striatum and (central) amygdala that have recently been implicated in the compulsive seeking and taking of alcohol and cocaine. The studies discussed here provide a promising line of research that will advance our knowledge of the neural circuits involved in the self-destructive behavior that characterizes drug addiction.

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Section: Neurobiological Mechanisms Of Compulsive Drug Use Ventral Anmentioning

confidence: 99%

Compulsive drug use and its neural substrates

Lesscher

Vanderschuren²

2012

Reviews in the Neurosciences

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“…In particular, the DA pathway projecting from the ventral tegmental area (V TA) to the nucleus accumbens (ACB) is thought to play a major role in mediating the rewarding effects of many stimuli, such as electrical brain stimulation and drugs of abuse (see Wise and Bozarth, 1987;Di Chiara, 1995). ACB DA depletion, produced by 6-OH DA, abolishes or attenuates intravenous self-administration of the indirect DA agonists amphetamine and cocaine (Roberts et al, 1977;Lyness et al, 1979;Pettit et al, 1984). Microinjection of DA antagonists into the ACB disrupts operant responding maintained by electrical brain stimulation (Mora et al, 1975;Mogenson et al, 1979;Stellar et al, 1983;Stellar and Corbett, 1989) and food (Ikemoto and Panksepp, 1996).…”

Section: Abstract: Dopamine D 1 Receptor; Dopamine D 2 Receptor; Skfmentioning

confidence: 99%

Role of Dopamine D₁and D₂Receptors in the Nucleus Accumbens in Mediating Reward

et al. 1997

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The objectives of this study were to examine the involvement of D 1 and D 2 receptors within the nucleus accumbens (ACB) in mediating reinforcement. The intracranial self-administration (ICSA) of D 1 and D 2 agonists was used to determine whether activating D 1 and/or D 2 receptors within the ACB of Wistar rats is reinforcing. At concentrations of 0.25, 0.50, and 1.0 mM (25, 50, and 100 pmol/100 nl of infusion), neither the D 1 agonist R(ϩ)- 3,4,] hydrochloride nor the D 2 agonist (Ϫ)-quinpirole (Quin) hydrochloride was self-administered into the shell region of the ACB. On the other hand, equimolar mixtures of SKF and Quin (SKFϩQuin), at concentrations of 0.25, 0.50, and 1.0 mM each, were significantly self-infused into the ACB shell. The core region of the ACB did not support the ICSA of SKFϩQuin at any of these concentrations. Rats increased lever pressing when the response requirement was increased from a fixed ratio 1 (FR1) to FR3, and they responded significantly more on the infusion lever than they did on the control lever. Coadministration of either 0.50 mM R(ϩ) -7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) hydrochloride, a D 1 antagonist, or 0.50 mM S(Ϫ)-sulpiride, a D 2 antagonist, completely abolished the ICSA of the mixture of SKFϩQuin (each at 0.50 mM) into the ACB shell. The present results suggest that concurrent activation of D 1 -and D 2 -type receptors in the shell of the ACB had a cooperative effect on DA-mediated reward processes.

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“…They each identified the best correlations for the rewarding effects of cocaine with DAT blockade. These authors also cited prior work from lesion studies [9][10][11][12] and electrical brain stimulation studies [13][14][15][16][17] reward mechanisms. These studies in turn built on prior pharmacologic blockade studies [18][19][20][21][22] that revealed altered psychostimulant self-administration with dopamine depletions or with dopamine receptor blocking drugs.…”

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confidence: 99%

Cocaine, reward, movement and monoamine transporters

Uhl¹,

Hall²,

Sora³

2002

Mol Psychiatry

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Recent evidence enriches our understanding of the molecular sites of action of cocaine reward and locomotor stimulation. Dopamine transporter blockade by cocaine appears a sufficient explanation for cocaine-induced locomotion. Variation in DAT appears to cause differences in locomotion without drug stimulation. However, previously-held views that DAT blockade was the sole site for cocaine reward have been replaced by a richer picture of multitransporter involvement with the rewarding and aversive actions of cocaine. These new insights, derived from studies of knockout mice with simultaneous deletions and/or blockade of multiple transporters, provide a novel model for the rewarding action of this heavily-abused substance and implicate multiple monoamine systems in cocaine's hedonic activities. Cocaine is a prototypical psychomotor stimulant that increases locomotor activity and elevates mood with rewarding euphoria.1 It also produces fearful and jittery aversive effects in many who take it.2,3 Cocaine blocks monoamine uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT) and norepinephrine (NET), and can also block ligand-and voltage-gated channels with somewhat lower potencies. 4 Understanding the relationships between cocaine's molecular actions and its psychomotor stimulant and aversive properties has remained surprisingly incomplete. This review focuses on recent advances in our understanding of the complex relationships between cocaine's molecular actions and its locomotor stimulant, rewarding and aversive properties.The 'DAT-is-it' hypothesis drove thinking about cocaine reward for at least a decade, ideas widely linked to Kuhar, Spealman and their colleagues 4-8 who gathered evidence from structure-activity relationships of transporter-blocking compounds with differential potencies at DAT, SERT and NET. They examined relationships between potencies of these compounds in tests of reward and binding affinities at each of the monoamine transporters. They each identified the best correlations for the rewarding effects of cocaine with DAT blockade. These authors also cited prior work from lesion studies 9-12 and electrical brain stimulation studies [13][14][15][16][17] This 'DAT-is-it' hypothesis was a major motivation for work that resulted in cloning DAT cDNAs, genes and gene variants in our laboratory and others. [23][24][25][26][27][28][29][30] It drove characterization and study of DAT gene variants in humans 29,31-53 and animal models. 54,55 It led to the production and characterization of DAT-over-and under-expressing and DAT-knockout mice strains. [56][57][58][59] These studies revealed an exquisite DAT-dependence of cocaine's locomotor stimulation. By contrast, they also produced surprising results that refuted the strong 'DAT-is-it' hypothesis of cocaine reward. Cocaine-induced locomotion: DAT is itDAT variation in humans and mice links robustly with variation in both baseline locomotion and/or psychostimulant-induced locomotor activities. Three strains of DAT knockout ...

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Destruction of dopaminergic nerve terminals in nucleus accumbens: Effect on d-amphetamine self-administration

Cited by 438 publications

References 11 publications

Compulsive drug use and its neural substrates

Compulsive drug use and its neural substrates

Role of Dopamine D₁and D₂Receptors in the Nucleus Accumbens in Mediating Reward

Cocaine, reward, movement and monoamine transporters

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Destruction of dopaminergic nerve terminals in nucleus accumbens: Effect on d-amphetamine self-administration

Cited by 438 publications

References 11 publications

Compulsive drug use and its neural substrates

Compulsive drug use and its neural substrates

Role of Dopamine D1and D2Receptors in the Nucleus Accumbens in Mediating Reward

Cocaine, reward, movement and monoamine transporters

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Role of Dopamine D₁and D₂Receptors in the Nucleus Accumbens in Mediating Reward