Different effects of nucleus accumbens and ventrolateral striatal dopamine depletions on instrumental response selection in the rat

Cousins, Michael S.; Sokolowski, Jonathan D.; Salamone, John D.

doi:10.1016/0091-3057(93)90226-j

Cited by 155 publications

(119 citation statements)

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“…In agreement with these observations, correlational analyses revealed a strong inverse relation between lever pressing and chow intake across drug treatments. This robust inverse correlation between lever pressing and chow intake in drug-treated animals has been a reliable statistical marker of the shift from lever pressing to chow intake that is induced by dopaminergic manipulations (Cousins et al 1993;Nowend et al 2001;Sink et al 2008). In view of these results, it appears as though the hypothesis that local stimulation of adenosine A 2A receptors could produce effects similar to interference with DA transmission was confirmed.…”

Section: Discussionmentioning

confidence: 71%

“…Finally, correlational analyses were used to measure the relation between lever pressing and chow consumption in rats treated with intra-accumbens CGS 21680. This correlational analysis has been conducted previously to provide an additional statistical marker of the shift from lever pressing to chow intake that was produced by interference with DA transmission (Cousins et al 1993;Sokolowski and Salamone 1998;.…”

Section: Discussionmentioning

confidence: 99%

“…Rats can choose between lever pressing on a FR5 schedule to obtain a preferred food or approaching and feeding upon a less preferred lab chow that is concurrently available. Untreated animals trained on this procedure generally receive most of their food by pressing the lever for food pellets and tend to eat little of the concurrently available but less preferred chow Cousins et al 1993Cousins et al , 1996Salamone et al 1995Nowend et al 2001;Farrar et al 2007). However, rats injected with low doses of DA antagonists or rats with accumbens DA depletions reallocate their behavior towards the less-effortful food-seeking behavior, i.e., animals with decreased lever pressing show a substantial increase in feeding upon the rodent chow Cousins et al 1993Sokolowski and Salamone 1998;Koch et al 2000;Nowend et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Untreated animals trained on this procedure generally receive most of their food by pressing the lever for food pellets and tend to eat little of the concurrently available but less preferred chow Cousins et al 1993Cousins et al , 1996Salamone et al 1995Nowend et al 2001;Farrar et al 2007). However, rats injected with low doses of DA antagonists or rats with accumbens DA depletions reallocate their behavior towards the less-effortful food-seeking behavior, i.e., animals with decreased lever pressing show a substantial increase in feeding upon the rodent chow Cousins et al 1993Sokolowski and Salamone 1998;Koch et al 2000;Nowend et al 2001). The results of these studies have been interpreted to mean that interference with nucleus accumbens DA transmission changes the pattern of choice behavior, altering the relative allocation of foodrelated responses away from lever pressing and towards approach and consumption of chow (Salamone et al 1997(Salamone et al , 2003.…”

Section: Discussionmentioning

confidence: 99%

“…Low-to-moderate doses of DA antagonists with different selectivity profiles, including haloperidol, cis-flupenthixol, SCH 23390, SCH 39166, raclopride, and eticlopride, all suppress lever pressing for food but actually increase chow intake Koch et al 2000;Sink et al 2008). In addition, rats with accumbens DA depletions or those treated with local intra-accumbens injections of DA antagonists also reallocate their responses in this task, showing decreases in lever pressing and increases in chow intake as a result of local interference with DA transmission Cousins et al 1993;Sokolowski and Salamone 1998;Koch et al 2000;Nowend et al 2001). These effects of interference with DA transmission differ substantially from the effects produced by pre-feeding to reduce food motivation , as well as appetite suppressants such as amphetamine , fenfluramine , and cannabinoid CB1 antagonists and inverse agonists (Sink et al 2008), all of which fail to shift behavior from lever pressing to chow intake.…”

Section: Introductionmentioning

confidence: 99%

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Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

et al. 2008

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Rationale-Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effortrelated processes, emerging evidence also implicates adenosine A 2A receptors.Objective-The present work was undertaken to test the hypothesis that accumbens A 2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism.Materials and methods-Three experiments assessed the effects of the adenosine A 2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions.Results-Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A 2A receptor agonist CGS 21680 (6.0-24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective.Conclusions-Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A 2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A 2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavior.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

et al. 2008

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Comparison of unilateral and bilateral intrastriatal 6‐hydroxydopamine‐induced axon terminal lesions: Evidence for interhemispheric functional coupling of the two nigrostriatal pathways

Roedter

Winkler

Samii

et al. 2001

J of Comparative Neurology

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Partial lesions of the nigrostriatal dopamine system can be induced reliably by the intrastriatal injection of 6-hydroxydopamine (6-OHDA) and are considered to be analogous to the early stages of human Parkinson's disease. Previous studies have established a clear correlation between different doses and placements of the 6-OHDA toxin and the degree of neurodegenerative changes and behavioral impairments. In the present study, the influence of the interdependence between the two nigrostriatal systems in both hemispheres on the effects on sensorimotor behavioral performances after terminal 6-OHDA lesions was investigated. The behavioral effects were correlated to the extent of nigral dopamine neuron cell and striatal tyrosine-hydroxylase (TH)-positive fiber loss. Sprague-Dawley rats receiving unilateral intrastriatal 6-OHDA injections (4 x 5 microg) exhibited a 30-70% reduction in striatal TH-positive fiber density along an anterior-posterior gradient, an 80% loss of nigral dopamine neurons and a mild degree of behavioral impairments as revealed by amphetamine-induced rotational asymmetry, and a reduced performance in the stepping and postural balance tests. When the same amount of toxin was injected twice into both hemispheres (2 x 4 x 5 microg), additional behavioral deficits were observed, consisting of a significant, but temporary, weight loss, a stable reduction in general locomotor activity and explorational behavior, and a long-term deficit in skilled forelimb use. This is interesting in light of the morphological findings, in which uni- and bilaterally lesioned animals did not differ significantly in the extent of TH-immunoreactive fiber and dopamine neuron loss within the nigrostriatal system in each lesioned hemisphere. These results indicate that the interdependent regulation of the two nigrostriatal systems may provide some compensatory support for the function and behavioral performance of the lesioned side via the normal unlesioned side, which is lost in animals with bilateral lesions of the nigrostriatal system. Therefore, this model of uni- and bilateral partial lesions of the nigrostriatal system, as characterized in the present study, may foster further exploration of compensatory functional mechanisms active in the early stages of Parkinson's disease and promote development of novel neuroprotective and restorative strategies.

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Characterization of Behavioral and Neurodegenerative Changes Following Partial Lesions of the Nigrostriatal Dopamine System Induced by Intrastriatal 6-Hydroxydopamine in the Rat

Kirik

Rosenblad

Björklund

1998

Experimental Neurology

601

429

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Different effects of nucleus accumbens and ventrolateral striatal dopamine depletions on instrumental response selection in the rat

Cited by 155 publications

References 50 publications

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

Comparison of unilateral and bilateral intrastriatal 6‐hydroxydopamine‐induced axon terminal lesions: Evidence for interhemispheric functional coupling of the two nigrostriatal pathways

Characterization of Behavioral and Neurodegenerative Changes Following Partial Lesions of the Nigrostriatal Dopamine System Induced by Intrastriatal 6-Hydroxydopamine in the Rat

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