Depletion of dopamine in the caudate nucleus but not in nucleus accumbens impairs reaction-time performance in rats

Amalric, Marianne; Gf, Koob

doi:10.1523/jneurosci.07-07-02129.1987

Cited by 187 publications

(121 citation statements)

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“…Previous investigators examining the effect of large bilateral depletion of striatal DA observed disruptions in reaction time performance, suggestive of difficulty with movement initiation (Amalric and Koob 1987;Amalric et al 1995;Moukhles et al 1994). In agreement, we also observed deficits that were associated with a preponderant loss of DA (у60%) in the striatum in comparison to the other brain structures innervated by the MFB.…”

Section: Discussionsupporting

confidence: 91%

“…Indeed, these animals did sustain a significant depletion of DA in limbic structures, particularly the nucleus accumbens, a brain region shown to be involved in reward and motivation. However, 6-OHDA lesions of the nucleus accumbens are reported not to have an effect on performance in the reaction time task (Amalric and Koob 1987). Moreover, we observed that animals in this group had difficulty handling the food pellet and would normally, without much success, attempt to consume the pellet while it was still in the food trough.…”

Section: Discussionmentioning

confidence: 59%

“…Moreover, deficits in reaction time have also been reported in Parkinson's disease (Evarts et al 1981;Gauntlett-Gilbert and Brown 1998;Berry et al 1999). These deficits appear to be mediated by the nigrostriatal dopaminergic pathway, as 6-OHDA-induced loss of SN neurons and striatal DA, and not accumbal DA, produces impairments in this task (Amalric and Koob 1987), and intrastriatal infusion of the DA receptor antagonist haloperidol has a comparable effect (Amalric and Koob 1989).Previous experiments have examined the effect of large 6-OHDA-induced lesions on performance in a simple and choice reaction time task. Because of the debilitating effects of bilateral lesions, the majority of these studies examined the effect of unilateral lesions on performance in the reaction time task.…”

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confidence: 94%

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Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Smith

Amalric²,

Koob

et al. 2002

Neuropsychopharmacology

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Overt symptoms of Parkinson's disease do not manifest themselves until there is a substantial loss of the dopaminergic nigrostriatal projection. However, as neuroprotective strategies are developed, it will be essential to detect the disease in its preclinical phase. Performance on conditioned reaction time tasks is known to be impaired by extensive 6-hydroxydopamine-induced lesions of theThe primary neuropathology of Parkinson's disease is the loss of dopamine (DA) neurons within the substantia nigra (SN) and massive depletion of DA in the striatum, the terminal region of the SN. This loss of DA appears to be responsible for the most prominent symptoms of Parkinson's disease. The degree of neurological deficit is related to the loss of striatal DA (Hornykiewicz and Kish 1987). The neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), used extensively to induce selective loss of DA neurons within the SN, provide animal models that share several of the characteristics of Parkinson's disease (see reviews by Zigmond and Keefe 1997;Jenner and Marsden 1986;Gerlach and Riederer NO . 6 Bilateral 6-OHDA on Reaction Time 7571996; Przedborski and Jackson-Lewis 1998). In addition, whereas intrastriatal injection of indirect DA agonists induces stereotypy (Costall et al. 1973;Statton and Solomon 1984), 6-OHDA lesions of the striatum block this stereotyped behavior (Price and Fibiger 1974). Finally, chronic administration of DA receptor antagonists produce extrapyramidal effects reminiscent of Parkinson's disease, and this is believed to be due to their action at D 2 receptors located in the striatum (Coffin et al. 1989). Although resting tremor and muscular rigidity are generally not reported in rodents after pharmacological manipulation of the nigrostriatal pathway, deficits in movement initiation and execution have been studied using several tests including a conditioned reaction time task. In this task, animals are typically required to respond in a particular way and within a limited period in order to receive a reward, such as a food pellet. This behavioral paradigm is responsive to pharmacological manipulation of dopaminergic neurotransmission mediated by the D 2 subtype of DA receptors Koob 1987, 1989;Amalric et al. 1993Amalric et al. , 1995Smith et al. 2000). For example, we have shown that low dose blockade of D 2 receptors, but not D 1 or D 3 receptors, decreased correct responses in the conditioned reaction time task, increased delayed responses, and lengthened reaction time in a manner suggestive of dysfunctions in movement initiation (Amalric et al. 1993;Smith et al. 2000). Moreover, deficits in reaction time have also been reported in Parkinson's disease (Evarts et al. 1981;Gauntlett-Gilbert and Brown 1998;Berry et al. 1999). These deficits appear to be mediated by the nigrostriatal dopaminergic pathway, as 6-OHDA-induced loss of SN neurons and striatal DA, and not accumbal DA, produces impairments in this task (Amalric and Koob 1987), and intrastriatal infusion...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 94%

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Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Smith

Amalric²,

Koob

et al. 2002

Neuropsychopharmacology

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“…The CP but not the ACC has been implicated in the initiation of rapid responses, because even moderate DA depletion of the CP impaired RT performance in rats (Amalric and Koob 1987). The medial subregion of the CP seems to be important for rapid movement initiation, since neurotoxic lesions of the medial but not of the lateral CP impaired RT performance of rats in the RT task used in the present study (Hauber and Schmidt 1994) and other RT tasks (Brown and Robbins 1989).…”

Section: Discussionmentioning

confidence: 61%

6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution

1994

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We examined the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions of the medial prefrontal cortex (PFC) in rats on motor initiation and execution in a simple reaction time task. Reaction times (RT) and movement times (MT) were measured in trained rats on four pre-and postoperative days. Animals with 6-OHDA lesions were selectively impaired on motor initiation as measured by a significant increase in RT on each postoperative day. Motor execution was intact postoperatively, since MT was not altered. Neurochemical analysis revealed a significant depletion of prefrontal dopamine (DA) and noradrenaline (NA) in lesioned animals. It was concluded that DA and, to a lesser extent, NA in the rat PFC were involved in monitoring RT performance.

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“…The effects of an intra-NAc NMDA and dopamine D 2 receptor blockade were examined in a lever release task for rats in which RTs of instrumental responses were a function of the expected food reward signaled in advance by discriminative instructive stimuli. Although it is well known that striatal NMDA and dopamine receptors play a key role in motor control (Hauber, 1996(Hauber, , 1998, the NAc does not control motor aspects of RT performance per se (Amalric and Koob, 1987;Brown and Robbins, 1989;Carli et al, 1989). Thus alterations of RTs induced by intra-NAc blockade of NMDA and dopamine D 2 receptors should reflect changes in the translation of motivational information into response speed.…”

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confidence: 99%

NMDA, But Not Dopamine D₂, Receptors in the Rat Nucleus Accumbens Are Involved in Guidance of Instrumental Behavior by Stimuli Predicting Reward Magnitude

2000

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Expectancy of future reward is an important factor guiding the speed of instrumental behavior. The present study sought to explore whether signals transmitted via the NMDA subtype of glutamate receptors and via dopamine D 2 receptors in the nucleus accumbens (NAc) are critical for the determination of reaction times (RTs) of instrumental responses by the expectancy of future reward. A simple RT task for rats demanding conditioned lever release was used in which the upcoming reward magnitude (5 or 1 pellet) was signaled in advance by discriminative stimuli. In trained rats, RTs of conditioned responses with expectancy of a high reward magnitude were found to be significantly shorter. The shortening of RTs by stimuli predictive of high reward to be obtained was dose-dependently impaired by bilateral intra-NAc infusion of the competitive NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV) (1, 2, or 10 g in 0.5 l/side), but not by infusion of the preferential dopamine D 2 antagonist haloperidol (5 and 12.5 g in 0.5 l/side) or by infusion of vehicle (0.5 l/side). In conclusion, the data reveal that in well trained animals stimulation of intra-NAc NMDA, but not of dopamine D 2 , receptors, is critically involved in guiding the speed of instrumental responses according to stimuli predictive of the upcoming reward magnitude.Key words: nucleus accumbens; goal-directed behavior; reward; dopamine; glutamate; reaction time; rat Reward expectancy is an important factor of guidance in adaptive motor behavior. Accordingly, the speed of instrumental responses has been found to be a function of the expected reward magnitude because reaction times (RTs) of rats were shortened by expectancy of signaled high reward (Brown and Bowman, 1995). Likewise, RTs of reaching movements (Hollerman et al., 1998) or saccadic eye movements (Kawagoe et al., 1998) of primates decreased as a function of the relative attractiveness of the expected reward.The nucleus accumbens (NAc) as an interface between limbic and motor structures (Groenewegen et al., 1996) may play a key role in the control of goal-directed actions by reward (Mogenson et al., 1980). It is generally assumed that the NAc subserves motivated behaviors such as feeding, sexual behavior, or exploratory locomotion elicited by primary reward and by conditioned stimuli associated with reward Everitt, 1990;Mitchell and Gratton, 1994;Watanabe, 1996). For instance, lesions of the NAc abolished conditioned place preference (Everitt et al., 1991), suggesting that environmental cues predictive for reward no longer control behavior. Furthermore, neurons in the striatum show reward expectation-related activations triggered by reward-predicting stimuli (Apicella et al., 1991;Schultz et al., 1992;Kawagoe et al., 1998). Depending on the expected type of reinforcer, behaviorrelated neuronal activity of striatal neurons is influenced differentially, implying that these neurons incorporate information about the expected behavioral outcome (Hollerman et al., 1998). Although these data suggest that ...

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Depletion of dopamine in the caudate nucleus but not in nucleus accumbens impairs reaction-time performance in rats

Cited by 187 publications

References 18 publications

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution

NMDA, But Not Dopamine D₂, Receptors in the Rat Nucleus Accumbens Are Involved in Guidance of Instrumental Behavior by Stimuli Predicting Reward Magnitude

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Depletion of dopamine in the caudate nucleus but not in nucleus accumbens impairs reaction-time performance in rats

Cited by 187 publications

References 18 publications

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution

NMDA, But Not Dopamine D2, Receptors in the Rat Nucleus Accumbens Are Involved in Guidance of Instrumental Behavior by Stimuli Predicting Reward Magnitude

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NMDA, But Not Dopamine D₂, Receptors in the Rat Nucleus Accumbens Are Involved in Guidance of Instrumental Behavior by Stimuli Predicting Reward Magnitude