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

Banasikowski, Tomek J; Bespalov, Anton; Drescher, Karla; Behl, Berthold; Unger, Liliane; Haupt, Andreas; Sullivan, James P.; Groß, Gerhard; Beninger, Richard J.

doi:10.1124/jpet.110.171348

Cited by 17 publications

(12 citation statements)

References 42 publications

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“…We then used independent groups in a 2 x 2 design with drug and phase (acquisition and expression) as the factors. Results showed a double dissociation with haloperidol blocking acquisition but not expression and ABT-127 blocking expression but not acquisition of conditioned activity based on cocaine (Banasikowski et al, 2007). These results support a differential role for Drd2 and Drd3 in establishment and expression of conditioned incentive learning.…”

Section: Mechanism Of Drd3 Involvement In Incentive Learningsupporting

confidence: 55%

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

Beninger

Banasikowski

2008

neurotox res

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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.

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Section: Mechanism Of Drd3 Involvement In Incentive Learningsupporting

confidence: 55%

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

Beninger

Banasikowski

2008

neurotox res

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“…These findings suggest that blockade of D 3 Rs impairs the capacity of the environmental cues that were associated with METH to elicit approach behaviors but does not alter the perceived appetitive value of METH. These results indicate that D 3 Rs play a more important role in the expression of incentive learning than in the acquisition of METH-induced CPP [47,50] . METH addiction is also characterized by persistent susceptibility to drug relapse [52] .…”

Section: Discussionmentioning

confidence: 80%

“…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] .…”

Section: Discussionmentioning

confidence: 81%

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

et al. 2015

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Aim:We have reported that a selective dopamine D 3 receptor antagonist YQA14 attenuates cocaine reward and relapse to drugseeking in mice. In the present study, we investigated whether YQA14 could inhibit methamphetamine (METH)-induced locomotor sensitization and conditioned place preference (CPP) in mice. Methods: Locomotor activity was monitored in mice treated with METH (1 mg/kg, ip) daily on d 4-13, followed by a challenge with METH (0.5 mg/kg) on d 21. CPP was examined in mice that were administered METH (1 mg/kg) or saline alternately on each other day for 8 days (METH conditioning). YQA14 was injected intraperitoneally 20 min prior to METH or saline. Results: Both repetitive (daily on d 4-13) and a single injection (on the day of challenge) of YQA14 (6.25, 12.5 and 25 mg/kg) dosedependently inhibited the acquisition and expression of METH-induced locomotor sensitization. However, repetitive injection of YQA14 (daily during the METH conditioning) did not alter the acquisition of METH-induced CPP, whereas a single injection of YQA14 (prior to CPP test) dose-dependently attenuated the expression of METH-induced CPP. In addition, the repetitive injection of YQA14 dosedependently facilitated the extinction and decreased the reinstatement of METH-induced CPP. Conclusion: Brain D 3 receptors are critically involved in the reward and psychomotor-stimulating effects of METH. Thus, YQA14 deserves further study as a potential medication for METH addiction.

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“…However, those results are difficult to interpret as the Cdk5 knock-out manipulation used in that experiment spanned the development and expression phases of conditioning, making it impossible to determine whether the effects observed were due to actions of the Cdk5 knock-out during acquisition, testing, or a combination of the two. Indeed, different neuronal mechanisms appear to underlie the induction and expression of excitatory conditioning [10–11] and these may be differentially regulated by Cdk5. Recently, we reported that inhibiting Cdk5 signaling in the NAcc exclusively during exposure to amphetamine prevented the accrual of contextual locomotor conditioning by amphetamine, indicating that Cdk5 actions in the NAcc are necessary for the induction of excitatory contextual associative conditioning [12].…”

Section: Reportmentioning

confidence: 99%

Inhibiting cyclin-dependent kinase 5 in the nucleus accumbens enhances the expression of amphetamine-induced locomotor conditioning

Singer

Forneris

Vezina

2014

Behavioural Brain Research

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When psychostimulant drugs like amphetamine are administered repeatedly in the presence of a contextual stimulus complex, long-lasting associations form between the unconditioned effects of the drug and the contextual stimuli. Here we assessed the role played by the proline-directed serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) in the nucleus accumbens (NAcc) on the expression of the conditioned locomotion normally observed when rats are returned to a context previously paired with amphetamine. Infusing the Cdk5 inhibitor roscovitine (40 nmol/0.5μl/side) into the NAcc 30-min before the test for conditioning significantly enhanced the conditioned locomotor response observed in rats previously administered amphetamine in the test environment. This effect was specific to the expression of a conditioned response as inhibiting Cdk5 produced no effect in control rats previously administered saline or previously administered amphetamine elsewhere. As inhibiting Cdk5 during exposure to amphetamine has been found to block the accrual of locomotor conditioning, the present results suggest distinct roles for NAcc Cdk5 in the induction and expression of excitatory conditioning by amphetamine.

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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

Cited by 17 publications

References 42 publications

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

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

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

Inhibiting cyclin-dependent kinase 5 in the nucleus accumbens enhances the expression of amphetamine-induced locomotor conditioning

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