Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training

AbstractRationaleThe dopamine system is important for incentive salience attribution, where motivational value is assigned to conditioned cues that predict appetitive reinforcers. However, the role of dopamine in this process may change with extended training.ObjectivesWe tested the effects of dopamine D1-like and D2-like receptor antagonism on the expression of sign-tracking and goal-tracking conditioned responses following extended Pavlovian conditioned approach (PCA) training. We also tested if amphetamine-induced psychomotor sensitization accelerates the shift to sign-tracking that is observed with extended training.MethodsIn experiment 1, 24 male Long-Evans rats received 20 PCA sessions in which one lever (CS+, 10 s) predicted 0.2 mL sucrose (10%, w/v) delivery and the other lever (CS–) did not. SCH-23390 (D1-like antagonist) or eticlopride (D2-like antagonist) were administered before non-reinforced behavioural tests at doses of 0, 0.01, and 0.1 mg/kg (s.c.). In experiment 2, rats received vehicle or 2 mg/kg amphetamine (i.p.) for 7 days (n = 12/group). Ten days later, they received 16 PCA training sessions.ResultsBoth doses of SCH-23390 reduced sign- and goal-tracking, but also reduced locomotor behaviour. A low dose of eticlopride (0.01 mg/kg) selectively reduced goal-tracking, without affecting sign-tracking or locomotor behaviour. Amphetamine produced psychomotor sensitization, and this did not affect the acquisition of sign- or goal-tracking.ConclusionsFollowing extended PCA training, dopamine D2-like receptor activity is required for the expression of goal-tracking but not sign-tracking. Psychomotor sensitization to amphetamine did not impact incentive salience attribution; however, more selective manipulations of the dopamine system may be needed.

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Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training

Behavioural Brain Research ◽

10.1016/j.bbr.2021.113238 ◽

2021 ◽

pp. 113238

Author(s):

Shaun Yon-Seng Khoo ◽

Alexandra Uhrig ◽

Anne-Noël Samaha ◽

Nadia Chaudhri

Keyword(s):

Dopamine Receptor ◽

Receptor Antagonism ◽

Extended Training ◽

Psychomotor Sensitization ◽

Goal Tracking

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Long-lasting contribution of dopamine in the nucleus accumbens core, but not dorsal lateral striatum, to sign-tracking

10.1101/132977 ◽

2017 ◽

Author(s):

Kurt M. Fraser ◽

Patricia H. Janak

Keyword(s):

Nucleus Accumbens ◽

Nigrostriatal System ◽

Dopamine Antagonist ◽

Incentive Salience ◽

Sprague Dawley ◽

Nucleus Accumbens Core ◽

Reversible Inactivation ◽

Sign Tracking ◽

Extended Training ◽

Accumbens Core

AbstractThe attribution of incentive salience to reward-paired cues is dependent on dopamine release in the nucleus accumbens core. These dopamine signals conform to traditional reward-prediction error signals and have been shown to diminish with time. Here we examined if the diminishing dopamine signal in the nucleus accumbens core has functional implications for the expression of sign-tracking, a Pavlovian conditioned response indicative of the attribution of incentive salience to reward-paired cues. Food-restricted male Sprague-Dawley rats were trained in a Pavlovian paradigm in which an insertable lever predicted delivery of food reward in a nearby food cup. After 7 or 14 training sessions, rats received infusions of saline, the dopamine antagonist flupenthixol (100 mM), or the GABA agonists baclofen and muscimol (0.5 mM baclofen/0.05 mM muscimol) into the nucleus accumbens core or the dorsal lateral striatum. Dopamine antagonism within the nucleus accumbens core attenuated sign-tracking, whereas reversible inactivation did not affect sign-tracking but increased non-specific food cup checking behaviors. Neither drug in the dorsal lateral striatum affected sign-tracking behavior. Critically, extended training did not alter these effects. Though extended experience with an incentive stimulus may reduce cue-evoked dopamine in the nucleus accumbens core, this does not alter the function of dopamine in this region to promote Pavlovian cue approach nor result in the recruitment of dorsal lateral striatal systems for this behavior. These data support the notion that dopamine within the mesoaccumbal system, but not the nigrostriatal system, contributes critically to incentive motivational processes independent of the length of training.AbbreviationsDLSdorsal lateral striatumGTgoal-trackerINintermediate responderNAcCnucleus accumbens coreSTsign-tracker

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Risk-Promoting Effects of Reward-Paired Cues in Human Sign- and Goal-Trackers

10.31234/osf.io/rxbpw ◽

2021 ◽

Author(s):

Mariya Cherkasova ◽

Eve Limbrick-Oldfield ◽

Luke Clark ◽

Jason J. S. Barton ◽

A. Jon Stoessl ◽

...

Keyword(s):

Eye Gaze ◽

Cost Benefit ◽

Incentive Salience ◽

Healthy Human ◽

Sign Tracking ◽

Reward Delivery ◽

Human Volunteers ◽

Within Subjects ◽

Goal Tracking

The incentive sensitization theory of addiction proposes that through repeated associations with addictive rewards, addiction-related stimuli acquire a disproportionately powerful motivational pull on behaviour. Animal research suggests trait-like individual variation in the degree of incentive salience attribution to reward-predictive cues, defined phenotypically as sign-tracking (high) and goal-tracking (low incentive salience attribution). While these phenotypes have been linked to addiction features in rodents, their translational validity has been little studied. Here, we examined whether sign- and goal-tracking in healthy human volunteers modulates the effects of reward-paired cues on cost-benefit decision making. Sign-tracking was measured in a Pavlovian conditioning paradigm as the amount of eye gaze fixation on the reward-predictive cue versus the location of impending reward delivery. In Study 1 (Cherkasova et al, 2018), participants were randomly assigned to perform a two-choice lottery task in which rewards were either accompanied (cued, n=63) or unaccompanied (uncued, n=68) by money images and casino jingles. In Study 2, participants (n=58) performed cued and uncued versions of the task in a within-subjects design. Across both studies, cues promoted riskier choice, and both studies yielded evidence of goal-tracking being associated with greater risk-promoting effects of cues. These findings are at odds with the notion of sign-trackers being preferentially susceptible to the influence of reward cues on behavior and point to the role of mechanisms besides incentive salience in mediating such influences.

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The attribution of incentive salience to Pavlovian alcohol cues: a shift from goal-tracking to sign-tracking

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2015.00054 ◽

2015 ◽

Vol 9 ◽

Cited By ~ 18

Author(s):

Chandra S. Srey ◽

Jean-Marie N. Maddux ◽

Nadia Chaudhri

Keyword(s):

Incentive Salience ◽

Sign Tracking ◽

Alcohol Cues ◽

Goal Tracking

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Effects of the cannabinoid receptor agonist CP-55,940 on incentive salience attribution

10.1101/767103 ◽

2019 ◽

Author(s):

Ali Gheidi ◽

Lora M. Cope ◽

Christopher J. Fitzpatrick ◽

Benjamin N. Froehlich ◽

Rachel Atkinson ◽

...

Keyword(s):

Cannabinoid Receptor ◽

High Dose ◽

Incentive Salience ◽

Prelimbic Cortex ◽

Sign Tracking ◽

Pavlovian Conditioned Approach ◽

Conditioned Approach ◽

Cp 55,940 ◽

Goal Tracking ◽

Cannabinoid Agonist

AbstractPavlovian conditioned approach paradigms are used to characterize the nature of motivational behaviors in response to stimuli as either directed toward the cue (i.e., sign-tracking) or the site of reward delivery (i.e., goal-tracking). Recent evidence has shown that activity of the endocannabinoid system increases dopaminergic activity in the mesocorticolimbic system, and other studies have shown that sign-tracking behaviors are dependent on dopamine. Therefore, we hypothesized that administration of a cannabinoid agonist would increase sign-tracking and decrease goal-tracking behaviors. Forty-seven adult male Sprague Dawley rats were given a low, medium, or high dose of the cannabinoid agonist CP-55,940 (N=12 per group) or saline (N=11) before Pavlovian conditioned approach training. A separate group of rats (N=32) were sacrificed after PCA training for measurement of cannabinoid receptor type 1 (CB1) and fatty acid amide hydrolase (FAAH) using in situ hybridization. Contrary to our initial hypothesis, CP-55,940 dose-dependently decreased sign-tracking and increased goal-tracking behavior. CB1 expression was higher in sign-trackers compared to goal-trackers in the prelimbic cortex, but there were no significant differences in CB1 or FAAH expression in the infralimbic cortex, dCA1, dCA3, dorsal dentate gyrus, or amygdala. These results demonstrate that cannabinoid signaling can specifically influence behavioral biases toward sign- or goal-tracking. Pre-existing differences in CB1 expression patterns, particularly in the prelimbic cortex, could contribute to individual differences in the tendency to attribute incentive salience to reward cues.

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