Attenuated Dopamine Efflux in the Rat Nucleus Accumbens During Successive Negative Contrast.

Genn, Rachel F.; Ahn, Soyon; Phillips, Anthony G.

doi:10.1037/0735-7044.118.4.869

Cited by 54 publications

(43 citation statements)

References 27 publications

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“…With experimenter-delivered drug, we have found that avoidance of a saccharin cue following a single saccharin-morphine pairing is accompanied by a full blunting of the accumbens dopamine response to the saccharin reward cue [69]. While negative contrast (reward devaluation) may contribute to this finding with dopamine [70], this blunting also could be explained by the onset of cue-induced craving and/ or withdrawal because accumbens dopamine levels also are blunted following the onset of naltrexone-induced withdrawal [71]. Second, using experimenter-delivered drug, we have found large individual differences whereby some rats are more likely to avoid intake of the drug-associated taste cue than are others and greater avoidance of the taste cue is associated with greater cue-induced elevation of circulating corticosterone [72].…”

Section: The Model: Experimenter Delivered Drugmentioning

confidence: 97%

Reward comparison: the Achilles’ heel and hope for addiction

Grigson

2008

Drug Discovery Today: Disease Models

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In the words of the late Charles Flaherty, reward comparison is commonplace. Rats and man, it appears, compare all rewards and this capacity likely contributes to our ability to select the most appropriate reward/behavior (food, water, salt, sex), at the most ideal level (e.g., a certain sweetness), at any given time. A second advantage of our predisposition for reward comparison is that the availability of rich alternative rewards can protect against our becoming addicted to any single reward/behavior. Thus, the potential protective effects of natural rewards/enrichment are addressed. Despite this, behavior can become inflexible when, through the development of addiction, stress, drug, or cues elicit craving, withdrawal, and ultimately, drug-seeking. Drug-seeking corresponds with a 'window of inopportunity', when even potent natural rewards have little or no impact on behavior. During this time, there is a unitary solution to the need state, and that solution is drug. The present animal model explores this 'window of inopportunity' when natural rewards are devalued and drug-seeking is engaged and considers a mode of possible intervention.

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Section: The Model: Experimenter Delivered Drugmentioning

confidence: 97%

Reward comparison: the Achilles’ heel and hope for addiction

Grigson

2008

Drug Discovery Today: Disease Models

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“…The effects of NAc injections of raclopride on flavor-nutrient learning were not investigated given the lack of effect obtained with systemic injections of the D2 antagonist. The NAc is a site at which sweet solutions in the mouth stimulate dopamine efflux (e.g., [12,16,17]). Whether IG sugar infusions also promote dopamine release in the NAc is not known.…”

Section: Discussionmentioning

confidence: 99%

“…The nucleus accumbens shell (NAcS) is a site in which sweet taste stimulates dopamine efflux (e.g., [12,16]), and where dopamine antagonists in the NAcS suppress lithium chloride-conditioned saccharin aversions [14]. Therefore, the present experiment examined whether dopamine D1 (SCH23390) or D2 (raclopride) antagonists administered bilaterally into the NAcS would dose-dependently alter the acquisition and/or expression of fructose-conditioned flavor-flavor preferences.…”

Section: Introductionmentioning

confidence: 99%

“…The sweet taste is considered to be an unconditioned stimulus (US) that reinforces the animal's preference for the added flavor, which represents the conditioned stimulus (CS). One neurochemical that is implicated in the reward value of sweet taste is dopamine, primarily because sweet taste activates mesolimbic dopamine circuits that are implicated in the mediation of natural as well as drug rewards (e.g., [16,17]). Dopamine receptor antagonism suppresses the intake of sweet solutions in rats [15,21,33], potentially because of its reduction of the hedonic value of sweet taste [24,29], or other factors such as changes in incentive salience (e.g., [8,9,20,23]).…”

Section: Introductionmentioning

confidence: 99%

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Role of dopamine D1 and D2 receptors in the nucleus accumbens shell on the acquisition and expression of fructose-conditioned flavor–flavor preferences in rats

Bernal

Dostova

Kest

et al. 2008

Behavioural Brain Research

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Systemic administration of dopamine D1 (SCH23390) and less so D2 (raclopride) receptor antagonists significantly reduce acquisition and expression of fructoseconditioned flavor preferences (CFP). Because dopamine in the nucleus accumbens shell (NAcS) is implicated in food reward, the present study examined whether NAcS D1 or D2 antagonists altered acquisition and/or expression of fructose-CFP. In Experiment 1, food-restricted rats with bilateral NAcS cannulae were trained to drink a fructose (8%) + saccharin (0.2%) solution mixed with one flavor (CS+/Fs) and a less-preferred 0.2% saccharin solution with mixed another flavor (CS−/s). Unlimited two-bottle tests with the two flavors in saccharin (0.2%: CS+/s, CS−/s) occurred 10 min following total bilateral NAcS doses of 0, 12, 24 or 48 nmol of SCH23390 or raclopride. Preference for CS+/s over CS−/s following vehicle treatment (76%) was significantly reduced by SCH23390 (48 nmol, 62%) and raclopride (24 nmol, 63%). In Experiment 2, rats received bilateral NAcS injections (12 nmol) of SCH23390 or raclopride on one-bottle training (16 ml) days. Yoked control rats received vehicle and were limited to the CS intakes of the D1 and D2 groups, whereas untreated controls without injections received their CS ration during training. Subsequent unlimited two-bottle tests revealed initial preferences of CS+/s over CS−/s in all groups that remained stable in untreated and yoked controls, but were lost over the 6 tests sessions in D1 and D2 groups. These data indicate that NAcS D1 and D2 antagonists

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“…Furthermore, rats treated with an ED regimen of D-amph failed to display successive positive contrast when shifted from 4 to 32% sucrose (Vacca and Phillips, 2005), a finding that parallels the enhancement of successive negative contrast observed in rats withdrawn from the same drug treatment . Genn et al (2004) have recently shown that DA efflux in the NAc was significantly attenuated when rats unexpectedly experience a reward of a lesser value in a negative contrast paradigm. Together, these data indicate that short-term abstinence from psychostimulants has a significant effect on the motivation to respond for natural rewards.…”

Section: Discussionmentioning

confidence: 99%

Effects of Short-Term Abstinence from Escalating Doses of D-Amphetamine on Drug and Sucrose-Evoked Dopamine Efflux in the Rat Nucleus Accumbens

Vacca

Ahn

Phillips

2006

Neuropsychopharmacol

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Abstinence from high doses of psychostimulant drugs, in both humans and rodents, is linked to adverse psychological effects including anhedonia, a core symptom of major depression, manifested behaviorally as decreased responding for rewarding stimuli. The present study used brain microdialysis in freely moving rats to examine the effect of D-amphetamine (D-amph) withdrawal on changes in extracellular dopamine (DA) levels in the nucleus accumbens (NAc) evoked by D-amph or behavior related to sucrose consumption. D-amph was administered intraperitoneally (i.p.) according to an escalating dose (ED) schedule (from 1 to 10 mg/kg, 3 doses/day). We first confirmed the development of tolerance by monitoring DA efflux in the NAc in response to 5 and 10 mg/kg doses of D-amph administered during the ED schedule of drug administration and again in response to the 5 mg/kg dose of D-amph 72 h following the last 10 mg/kg D-amph injection. In a separate study, DA efflux in the NAc was first shown to be increased significantly during both preparatory and consummatory phases of responding for a 4% sucrose solution. Withdrawal from the ED schedule of D-amph caused a selective attenuation of DA efflux only during the preparatory phase of the sucrose test. These results provided convincing evidence of neurochemical adaptation within the mesocorticolimbic DA pathway during and following the administration of an ED schedule of D-amph as well as suppressed neurochemical responses to a psychostimulant drug and cues associated with a natural reward after withdrawal from drug treatment. Accordingly, these findings support the hypothesis that downregulation of mesocorticolimbic DA function maintained during D-amph withdrawal may account for the selective disruption of motivated behavior reported in studies employing psychostimulant drug withdrawal as a model of depression in rodents. Neuropsychopharmacology (2007) 32, 932-939.

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Attenuated Dopamine Efflux in the Rat Nucleus Accumbens During Successive Negative Contrast.

Cited by 54 publications

References 27 publications

Reward comparison: the Achilles’ heel and hope for addiction

Reward comparison: the Achilles’ heel and hope for addiction

Role of dopamine D1 and D2 receptors in the nucleus accumbens shell on the acquisition and expression of fructose-conditioned flavor–flavor preferences in rats

Effects of Short-Term Abstinence from Escalating Doses of D-Amphetamine on Drug and Sucrose-Evoked Dopamine Efflux in the Rat Nucleus Accumbens

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