Dopaminergic mechanism of reward-related incentive learning: Focus on the dopamine d3 receptor

Abstract

Dopamine D(3) receptors (Drd3) have been implicated in the control of responding by drug-related conditioned incentive stimuli. We review recent studies of the effects of Drd3 antagonists or partial agonists on the control of self-administration of intravenous (IV) cocaine, IV morphine and oral ethanol on reward-rich and lean schedules, in reinstatement tests, on second-order schedules and on the acquisition and expression of conditioned place preference (CPP) and conditioned motor activity. For comparison, related studies where conditioned stimuli are based on nutritional reward also are considered. When self-administration depends more heavily on conditioned cues for its maintenance, for example on second-order schedules or lean ratio schedules, Drd3 antagonists or partial agonists reduce responding. Although data are limited, similar effects may be seen for responding for cues based on drugs or nutritional rewards. Drd3 agents also block the ability of conditioned cues to reinstate responding for cocaine or food. Published results suggest that Drd3 plays a more important role in the expression than in the acquisition of a CPP or conditioned motor activity. The mechanism mediating the role of Drd3 in the control of responding by conditioned incentive stimuli remains unknown but it has been found that Drd3 receptors increase in number in the nucleus accumbens during conditioning. Perhaps Drd3 participates in the molecular mechanisms underlying the role of dopamine and of dopamine receptor subtypes in reward-related incentive learning.

A selective D3 receptor antagonist YQA14 attenuates methamphetamine-induced behavioral sensitization and conditioned place preference in mice

“…These results suggest that D 3 Rs play a more important role in the expression of conditioned behaviors than in their acquisition [47,50] . Regardless of the mechanisms underlying the ineffectiveness of YQA14 at combatting the acquisition of METH-induced CPP, the present finding that YQA14 inhibits the expression of METH-induced CPP is consistent with previous reports that have shown that the blockade of D 3 Rs by SB-277011A, YQA14 or SR21502 inhibits cocaine-induced CPP [14,22,51] , cocaine and METH self-administration [12,18,21,31] , and cocaine-and METHinduced enhancement of electrical brain stimulation rewards [21,33,35] .…”

“…Accordingly, during the conditioning sessions, the stimuli in the chamber was associated with the METH to display the perceived appetitive. However, on the expression day, the animals that did not receive METH spent more time in the drug-paired chamber because of this incentivized learning [47][48][49] .…”

Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

“…We would hypothesize that pramipexole's activity at the D2 receptors could readily explain enhancement on attention and working memory tasks that are closely linked with the availability of DA in the PFC (Badre, 2012). In contrast, D3 receptors are most widely distributed in regions involved in reward-based learning (Beninger and Banasikowski, 2008), which might be more directly relevant for task performance on emotional decision-making measures, such as the IGT. D3 receptors are primarily expressed in the mesocorticolimbic DA pathway, and structures in this circuitry show increased activation during impulsive decision making (see Madden et al, 2010 for review).…”

Double Dissociation of the Effects of Haloperidol and the Dopamine D3 Receptor Antagonist ABT-127 on Acquisition vs. Expression of Cocaine-Conditioned Activity in Rats

“…Our results with conditioned activity are consistent with related studies using stimulant self-administration, reinstatement, or conditioned place preference (CPP) techniques. We recently reviewed these studies (Beninger and Banasikowski, 2008) and will provide an overview of the results here. In self-administration studies, when the maintenance of responding relied heavily on conditioned stimuliin the ventral caudate and NAc core (Neisewander et al, 2004).…”

“…However, during the expression test, pimozide (Beninger and Hahn, 1983;Beninger and Herz, 1986) and raclopride (Fontana et al, 1993 but see Cervo and Samanin, 1996) failed to block the expression of conditioned activity. Results suggest that D2 receptors play a more important role in acquiring conditioning than in its expression during the test phase (see Beninger and Banasikowski, 2008).…”