Functional implications of dopamine D1 vs. D2 receptors: A ‘prepare and select’ model of the striatal direct vs. indirect pathways

Keeler, J.F.; Pretsell, Douglas; Robbins, Trevor W.

doi:10.1016/j.neuroscience.2014.07.021

Cited by 119 publications

(128 citation statements)

References 75 publications

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“…Furthermore, in models of obesity featuring increased sucrose consumption, selective D2 receptor antagonists are considerably more effective than D1 antagonists at reducing sucrose intake without reducing levels of overall behavior (Hajnal et al , 2007). These studies are consistent with the proposal that D1 systems process an array of possible behavioral actions which can be rapidly executed, whereas D2 systems integrate more complex information regarding current physiological needs and motivations (for recent discussion of the possible roles of D1/D2 systems, see: (Keeler et al , 2014)). The association between D2 systems and sucrose intake, and the known effect of ibotenic PPTg lesions to enhance D2 mediated behaviors, adds support to the possibility that sucrose overconsumption in PPTg lesioned rats might be reflective of an altered response to DA signaling, and in particular an increased propensity to engage in D2 driven behavior.…”

Section: Discussionsupporting

confidence: 85%

Enhanced consumption of salient solutions following pedunculopontine tegmental lesions

et al. 2015

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Rats with lesions of the pedunculopontine tegmental nucleus (PPTg) reliably overconsume high concentration sucrose solution. This effect is thought to be indicative of response-perseveration or loss of behavioral control in conditions of high excitement. While these theories have anatomical and behavioral support, they have never been explicitly tested. Here, we used a contact lickometer to examine the microstructure of drinking behavior to gain insight into the behavioral changes during overconsumption. Rats received either excitotoxic (ibotenic acid) damage to all PPTg neuronal subpopulations or selective depletion of the cholinergic neuronal sub-population (Dtx-UII lesions). We offered rats a variety of pleasant, neutral and aversive tastants to assess the generalizability and specificity of the overconsumption effect. Ibotenic lesioned rats consumed significantly more 20% sucrose than sham controls, and did so through licking significantly more times. However, the behavioral microstructure during overconsumption was unaffected by the lesion and showed no indications of response-perseveration. Furthermore, the overconsumption effect did not generalize to highly consumed saccharin. In contrast, while only consuming small amounts of quinine solution, ibotenic lesioned rats had significantly more licks and bursts for this tastant. Selective depletion of cholinergic PPTg neurons had no effect on consumption of any tastant. We then assessed whether it is the salience of the solution which determines overconsumption by ibotenic lesioned rats. While maintained on free-food, ibotenic lesioned rats had normal consumption of sucrose and hypertonic saline. After mild food deprivation ibotenic PPTg lesioned rats overconsumed 20% sucrose. Subsequently, after dietary induced sodium deficiency, lesioned rats consumed significantly more saline than controls. These results establish that it is the salience of the solution which is the determining factor leading to overconsumption following excitotoxic PPTg lesion. They also find no support for response-perseveration contributing to this effect. Results are discussed in terms of altered DA and salience signaling.

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Section: Discussionsupporting

confidence: 85%

Enhanced consumption of salient solutions following pedunculopontine tegmental lesions

et al. 2015

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“…Especially relevant to the EE-mediated effects on DARPP32 in the nucleus accumbens core, studies could delineate effects specific to direct or indirect projection pathways 41 or ensembles affected by incubation and/or EE 42 . In addition, functional roles of the protein changes we observed should be conducted, although at this time there is no ligand specific for the DARPP32 protein other than antibodies.…”

Section: Discussionmentioning

confidence: 99%

Sucrose Abstinence and Environmental Enrichment Effects on Mesocorticolimbic DARPP32 in Rats

Grimm

Glueck

Ginder

et al. 2018

Sci Rep

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Dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP32) is a signaling molecule that could serve as a molecular switch, promoting or restraining sucrose seeking. We measured DARPP32 and pThr34 DARPP32 in the brains of male Long-Evans rats with a history of sucrose self-administration followed by 1 or 30 days of abstinence and exposure to either overnight (acute) or one month (chronic) environmental enrichment (EE). Brains were extracted following a 1 h cue reactivity test or no exposure to the test environment. Micropunches (prelimbic, infralimbic, and anterior cingulate areas of the medial prefrontal cortex, orbitofrontal cortex, dorsal striatum, nucleus accumbens, and ventral tegmental area) were then processed using Western blot. Abstinence increased, while EE decreased, sucrose seeking. DARPP32 and pThr34 DARPP32 levels were affected by testing, abstinence, and/or EE in most regions. Especially salient results were observed in the nucleus accumbens core, a region associated with relapse behaviors. Both acute and chronic EE reduced DARPP32 in the nucleus accumbens core and acute EE increased the ratio of phosphorylated to total DARPP32. Degree of DARPP32 phosphorylation negatively correlated with sucrose seeking. These findings demonstrate a potential role for DARPP32 in mediating the “anti-craving” effect of EE.

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“…D1 and D2 signaling in the striatum regulate overlapping yet dissociable aspects of reward learning and effort-based decision making (Izquierdo et al 2006; Schweimer and Hauber, 2006; Groman et al 2011; Stopper et al 2013; Keeler et al 2014; Yohn et al 2015). The adolescent period is marked by decreased density of both types of receptors in the striatum (Gelbard et al 1989; Teicher et al 1995; Tarazi and Baldessarini 2000).…”

Section: Discussionmentioning

confidence: 99%

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

Izquierdo

Pozos

Torre

et al. 2016

Behavioural Brain Research

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Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner.

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Functional implications of dopamine D1 vs. D2 receptors: A ‘prepare and select’ model of the striatal direct vs. indirect pathways

Cited by 119 publications

References 75 publications

Enhanced consumption of salient solutions following pedunculopontine tegmental lesions

Enhanced consumption of salient solutions following pedunculopontine tegmental lesions

Sucrose Abstinence and Environmental Enrichment Effects on Mesocorticolimbic DARPP32 in Rats

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

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