N-methyl-D-aspartate receptor-dependent plasticity within a distributed corticostriatal network mediates appetitive instrumental learning.

Baldwin, Anne E.; Holahan, Matthew R.; Sadeghian, Kenneth; Kelley, Ann E.

doi:10.1037/0735-7044.114.1.84

Cited by 104 publications

(90 citation statements)

References 88 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have shown in previous reports, however, differential effects of drug infusions on performance of instrumental lever-pressing in these two structures, thereby attenuating some of these concerns. For example, lever-pressing was reduced by an infusion of the NMDA receptor antagonist AP-5 into the CeA prior to session 11 (Andrzejewski et al, 2004), but not by an AP-5 infusion into the BLA (Baldwin et al, 2000). These results suggest that regional specificity has been produced under conditions and methods that are identical to the present experiments.…”

Section: D1 Receptor Activation In the Amygdala Is Required For Instrsupporting

confidence: 66%

“…Therefore, while lesion-induced deficits in certain paradigms are well-documented, the lack of deficits in some lesion studies makes them difficult to interpret, given the likely recovery of function. The fact that selective pharmacological blockade of NMDA receptors (Andrzejewski et al, 2004;Baldwin et al, 2000), muscarinic receptors (See et al, 2003) and now D1 receptors, within the amygdala, disrupts aspects of appetitive instrumental learning indeed demonstrates a role for the amygdala in the cellular plasticity that underlies this learning.…”

Section: Discrepancies Between Pharmacological and Lesion Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

2005

View full text Add to dashboard Cite

Substantial experimental evidence exists suggesting a critical role for dopamine in reinforcer-related processes, such as learning and drug addiction. Dopamine receptors, and in particular D1 receptors, are widely considered as modulators of synaptic plasticity. The amygdala contains both dopamine terminals and dopamine D1 receptors and is intimately involved in motivation and learning. However, little is known about the involvement of D1 receptor activation in two subnuclei of the mammalian amygdala, the central nucleus and basolateral complex in instrumental learning. Following recovery from surgery and preliminary training, rats with bilateral indwelling cannulae aimed at the central nucleus or basolateral complex were trained to lever-press for sucrose pellets over 12 sessions. Infusion of the selective D1 antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (0.3 nmol and 3.0 nmol) prior to the first five training sessions dose-dependently impaired instrumental learning when compared with vehicleinfused controls. All rats were then exposed to five sessions drug-free; lever-pressing quickly reached equal levels across groups. A drug infusion prior to an 11th session revealed no effect on performance. Control experiments indicated that basic motivational processes and general motor responses were intact, such as spontaneous feeding and locomotor activity. These results show an essential role for D1-receptor activation in both the central nucleus and basolateral complex on the acquisition of lever pressing for sucrose pellets in rats, but not the performance of the behavior once conditioned. We propose that instrumental learning is dependent on plasticity in the central nucleus and basolateral complex amygdala, and that D1 receptor activation participates in transcriptional processes that underlie this plasticity.Keywords instrumental learning; amygdala; dopamine; D1; plasticity; rats Biologically important events, such as procurement of food, escape from predation, and access to sexual partners, often require flexible patterns of behavior in order to produce themforaging, vigilance, and defense, for example. Important biological reinforcers (Reinf), in turn, change the behavior that produced them, illustrating a form of adaptability termed "instrumental learning." Many Reinf-related processes are mediated by the mesocorticolimbic dopamine (DA) system, consisting of DA neurons in the ventral tegmental area and their projections to the nucleus accumbens, medial prefrontal cortex, striatum, amygdala and other *Corresponding author. Tel: +1-608-262-9332. E-mail address: mandrzejewsk@wisc.edu (M. E. Andrzejewski). (Beninger and Miller, 1998;Cardinal et al., 2002;Kelley and Berridge, 2002). Specifically, studies have shown that D1 receptor activation throughout this corticolimbicstriatal network plays a critical role in learning (Beninger and Gerdjikov, 2004). Indeed, D1 receptor activation is thought to serve a crucial modulatory function in the induction o...

show abstract

Section: D1 Receptor Activation In the Amygdala Is Required For Instrsupporting

confidence: 66%

Section: Discrepancies Between Pharmacological and Lesion Studiesmentioning

confidence: 99%

Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

2005

View full text Add to dashboard Cite

show abstract

“…In contrast, when 5-HT 6 receptors were overexpressed in the dorsal central region of the striatum, the rats demonstrated intact learning of the instrumental conditioning. Pharmacological blockade of the medial prefrontal cortex, a region which projects to the dorsomedial striatum (Sesack et al, 1989), produces also deficits in instrumental conditioning (Baldwin et al, 2000). The dorsal central region receives inputs from the agranular cortex and lateral orbital cortex, regions important for reversal learning but not setshifting or habituation (Reep et al, 2003;Dalley et al, 2004), and thus it is likely that these subregional differences in corticostriatal projections may underlie the differential behavior observed .…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of 5-HT6 Receptors in the Rat Dorsomedial Striatum Impairs Instrumental Learning

Mitchell

Sexton

Neumaier

2006

Neuropsychopharmacol

View full text Add to dashboard Cite

A number of studies have shown that systemic 5-HT 6 receptor antagonists can improve learning and memory, but the mechanism for these observations is not known. As striatum normally expresses 5-HT 6 receptors abundantly and is important in consolidating stimulusresponse learning, we used targeted gene delivery to further increase the expression of 5-HT 6 receptors in rat striatum and then examined learning. Increased 5-HT 6 expression had no effect on performance in the Morris water maze, a hippocampal-dependent learning paradigm, and did not alter the latency to approach or consume sucrose tablets. However, rats with increased 5-HT 6 expression failed to acquire a reward-based instrumental learning task, a striatum-dependent learning model, during 3 days of successive sessions as compared to sham surgery or GFP-expressing control rats. This behavioral deficit was observed in rats overexpressing 5-HT 6 receptors in the dorsomedial striatum, but not in rats with increased dorsocentral striatal expression. The 5-HT 6 receptor-associated deficit was reversed by administration of a 5-HT 6 antagonist, SB-258585, before each training session. When animals learned the instrumental learning task before gene transfer, increased 5-HT 6 receptor expression had no effect on long-term recall or performance of the task or on extinction of operant responding. Thus, 5-HT 6 receptor activity in rat striatum disrupts acquisition of new instrumental learning but does not impair memory or performance of reward-motivated behavior once established.

show abstract

“…While the link between the effects of these compounds on cortical dopaminergic transmission and behavior remains elusive, evidence supports a significant relationship. Prefrontal dopamine is an important modulator of working memory (Sawaguchi and Goldman-Rakic, 1991) and instrumental learning (Baldwin et al, 2000(Baldwin et al, , 2002. While dopamine release is necessary for proper mnemonic function, excessive prefrontal dopamine release, such as that induced by NMDA antagonists (Verma and Moghaddam, 1996), can also impair cognitive performance (Arnsten et al, 1994).…”

Section: Mglu5-nmda Receptor Interactionmentioning

confidence: 99%

Functional Interaction Between NMDA and mGlu5 Receptors: Effects on Working Memory, Instrumental Learning, Motor Behaviors, and Dopamine Release

Homayoun

Stefani

Adams

et al. 2004

Neuropsychopharmacol

228

182

View full text Add to dashboard Cite

Pharmacological manipulation of N-methyl-D-aspartate (NMDA) receptors may be critical for the treatment of many neurological and psychiatric disorders. Metabotropic glutamate (mGlu5) receptors are abundant in corticolimbic circuitry, where they modulate NMDA receptor-mediated signal transduction. Therefore, pharmacological manipulation of mGlu5 receptor may provide a treatment strategy for cognitive disorders that are associated with NMDA receptor dysfunction. We sought to determine whether the recently described molecular and cellular interactions between NMDA and mGlu5 receptors coregulate higher order behaviors. We examined the interaction of the selective mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and the use-dependent NMDA antagonist MK-801, on locomotion, stereotypy, working memory, instrumental learning, and corticolimbic dopamine release. MPEP, at 10 mg/kg, but not 3 mg/kg, impaired working memory and instrumental learning, transiently increased dopamine release in prefrontal cortex and nucleus accumbens, and augmented the effect of MK-801 on cortical dopamine release, locomotion, and stereotypy. Pretreatment with 3 mg/kg of MPEP enhanced the detrimental effects of MK-801 on cognition. These results demonstrate that an mGlu5 receptor antagonist can potentiate the motoric, cognitive, and dopaminergic effects of an NMDA receptor antagonist. Thus, mGlu5 receptors appear to play a major role in regulating NMDA receptor-dependent cognitive functions such as learning and working memory. By extension, these results suggest that pharmacological potentiation of mGlu5 receptors may ameliorate the cognitive and other behavioral abnormalities associated with NMDA receptor deficiency.

show abstract

N-methyl-D-aspartate receptor-dependent plasticity within a distributed corticostriatal network mediates appetitive instrumental learning.

Cited by 104 publications

References 88 publications

Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

Increased Expression of 5-HT6 Receptors in the Rat Dorsomedial Striatum Impairs Instrumental Learning

Functional Interaction Between NMDA and mGlu5 Receptors: Effects on Working Memory, Instrumental Learning, Motor Behaviors, and Dopamine Release

Contact Info

Product

Resources

About