The dopamine D3 receptor partial agonist, BP 897, is an antagonist at human dopamine D3 receptors and at rat somatodendritic dopamine D3 receptors

Wicke, Karsten; Garcia-Ladona, Javier

doi:10.1016/s0014-2999(01)01054-8

Cited by 73 publications

(73 citation statements)

References 21 publications

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“…Therefore, the impairment of the establishment of food CPP by these full agonists unlikely resulted from primary actions on feeding behavior, but very probably involved stimulusreward associations. Interestingly, the doses of 7-OH-DPAT (0.5-2 mg/kg) and quinelorane (1 mg/kg) active to prevent food CPP were in the range of their ED 50 for inhibition of DA neuron firing in the ventral tegmental area and/or substantia nigra (Liu et al, 1994;Kreiss et al, 1995;Lejeune and Millan, 1995;Wicke and Garcia-Ladona, 2001). Since the latter effect has been claimed to be more closely related to drug affinity at D 3 than D 2 receptors (Kreiss et al, 1995), this supports a preferential role for D 3 R in the action of very low doses of full D 2-like agonists.…”

Section: Discussionmentioning

confidence: 99%

“…In vivo, BP 897 acts as a D 3 R partial agonist or antagonist, at low doses, and as a weak D 2 R antagonist at doses above 10 mg/kg (Pilla et al, 1999;Wood et al, 2000;Wicke and Garcia-Ladona, 2001). It was not selfadministered by cocaine-experienced rats and monkeys, did not generalize from cocaine or d-amphetamine discriminative stimulus in rats, and did not support CPP in mice (Pilla et al, 1999;Beardsley et al, 2001;Francès et al, 2003), indicating that it is devoid of positive reinforcing potential.…”

Section: Introductionmentioning

confidence: 99%

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Effects of a Dopamine D3 Receptor Ligand, BP 897, on Acquisition and Expression of Food-, Morphine-, and Cocaine-induced Conditioned Place Preference, and Food-seeking Behavior in Rats

Duarte

Lefebvre

Chaperon

et al. 2003

Neuropsychopharmacol

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The present study addressed the role of dopaminergic D 3 receptors (D 3 R) in motivational processes in rats. The effects of the selective D 3 R partial agonist, BP 897 (0.25-1 mg/kg, i.p.), on the establishment and the expression of conditioned place preference (CPP) supported by food, morphine (4 mg/kg, s.c.), or cocaine (2 mg/kg, s.c.) were investigated using an unbiased, one-compartment, placeconditioning procedure. When administered alone, BP 897 (0.05-2 mg/kg, i.p.) did not support CPP; on the contrary, conditioned place avoidance (CPA) was observed at 1 mg/kg, suggesting that this dose of BP 897 could be perceived as aversive. When given before each cocaine injection during the conditioning phase, BP 897 (1 mg/kg) prevented the establishment of CPP, and a single administration of BP 897 (0.5 and 1 mg/kg) before the test session impaired the expression of cocaine CPP. In contrast, neither the establishment nor the expression of food-and morphine-CPP were significantly altered by BP 897 (up to 1 mg/kg), whereas the full but less selective D 3 /D 2 R agonists, 7-OH-DPAT (0.5-2 mg/kg, s.c.) and quinelorane (1 mg/kg, s.c.), prevented the acquisition of food CPP. In a within-session extinction schedule of lever pressing for food, BP 897 (0.06-2 mg/kg) was ineffective in potentiating response reinstatement induced by the noncontingent delivery of two food pellets, in contrast with quinelorane and 7-OH-DPAT where previous studies showed to be efficient in this respect (Duarte et al, 2003). These results indicate that BP 897 has no positive appetitive value on its own, and that a moderate degree of stimulation of D 3 R is not sufficient to modulate food-primed food-seeking behavior or alter incentive motivation for food, morphine, and/or their associated cues. However, D 3 R are likely involved in the perception of the rewarding value of cocaine and cocaine-paired cues. This suggests that the appetitive effects of cocaine are subserved by mechanisms different, at least in part, from those of morphine and food, and that D 3 R play a role only in the former.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of a Dopamine D3 Receptor Ligand, BP 897, on Acquisition and Expression of Food-, Morphine-, and Cocaine-induced Conditioned Place Preference, and Food-seeking Behavior in Rats

Duarte

Lefebvre

Chaperon

et al. 2003

Neuropsychopharmacol

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“…This is also consistent with previous studies demonstrating that BP-897 produces an aversive-like effect, as assessed in the BSR and conditioned place preference/aversion paradigms (Duarte et al 2003;Gyertyán and Gál 2003;Campos et al 2004). In addition, BP-897 also produces a compensatory increase in cocaine self-administration (Gyertyán and Gál 2003), and inhibits quinpirole (a mixed D 2 / D 3 receptor agonist)-induced inhibition of DA neuronal firing in the substantia nigra, similar to the D 2 receptor antagonist haloperidol (Wicke and Garcia-Ladona 2001).…”

Section: Bp-897 Has Anti-addictive and Other Unwanted Effectsmentioning

confidence: 99%

The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats

Spiller

Peng

et al. 2007

Psychopharmacology

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Rationale-We have previously reported that selective antagonism of brain D 3 receptors by SB-277011A or NGB 2904 significantly attenuates cocaine-or nicotine-enhanced brain stimulation reward (BSR).Objective-In the present study, we investigated whether the selective D 3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D 3 agonist BP-897 similarly reduce methamphetamine (METH)-enhanced BSR.Materials and methods-Rats were trained to respond for rewarding electrical self-stimulation of the medial forebrain bundle. To assess the degree of drug-induced changes in BSR, a ratefrequency curve shift paradigm was used to measure brain-reward threshold (θ 0 ). © Springer-Verlag 2007Correspondence to: Zheng-Xiong Xi. Conflict of interest statementThere are no personal financial holdings that could be perceived as constituting a potential conflict of interest. NIH Public AccessAuthor Manuscript Psychopharmacology (Berl). Author manuscript; available in PMC 2013 July 17. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResults-METH (0.1-0.65 mg/kg, i.p.) dose-dependently lowered (~10-50%) BSR thresholds, producing an enhancement of BSR. Pretreatment with SB-277011A (12 mg/kg, but not 24 mg/kg, i.p.) significantly attenuated METH-enhanced BSR. NGB 2904 (0.1-1.0 mg/kg, but not 10 mg/kg) also attenuated METH-enhanced BSR. SB-277011A or NGB 2904 alone, at the doses tested, had no effect on BSR. Pretreatment with BP-897 (0.1-5 mg/kg) dose-dependently attenuated METHenhanced BSR. However, when the dose was increased to 10 mg/kg, BP-897 shifted the stimulation-response curve to the right (inhibited BSR itself) in the presence or absence of METH.Conclusions-Selective antagonism of D 3 receptors by SB-277011A or NGB 2904 attenuates METH-enhanced BSR in rats, while the METH-enhanced BSR attenuation produced by BP-897 may involve both D 3 and non-D 3 receptors. These findings support a potential use of selective D 3 receptor antagonists for the treatment of METH addiction.

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“…This suggestion is consistent with our findings that NGB 2904 or SB-277011A had no effect on cocaine self-administration under continuous FR reinforcement conditions in which a high cumulative dose is easily built up, but significantly inhibited cocaine self-administration under PR reinforcement conditions in which a high cumulative dose of drug is difficult to achieve (Di Ciano et al, 2003;Gilbert et al, 2003). Similarly, BP-897 (a D 3 partial agonist whose antagonist properties may predominate; see Wood et al, 2000;Wicke and Garcia-Ladona, 2001) also fails to inhibit cocaine self-administration under FR reinforcement conditions, but significantly inhibits cocaine-seeking behavior under second-order reinforcement conditions (Pilla et al, 1999), under which the brain's DA response to the cocaineassociated cues that drive second-order reinforced drugseeking behavior is substantially lower than to cocaine itself (ie approximately a 25% increase in accumbens DA produced by cocaine-associated cues (Gerasimov et al, 2001) vs approximately a 200-800% increase in accumbens DA produced by either exogenously or self-administered cocaine (Wise et al, 1995;Dewey et al, 1997)). …”

Section: Ngb 2904's Attenuation Of Cocaine-enhanced Bsrmentioning

confidence: 99%

“…This compound has structural similarity to BP-897 (Pilla et al, 1999;Wood et al, 2000;Wicke and Garcia-Ladona, 2001), and binds with high affinity to cloned primate D 3 receptors (K i 1.4 nM) (Yuan et al, 1998;Robarge et al, 2001). NGB 2904 is reported to have 155-fold selectivity for primate D 3 over primate D 2 receptors, and 4800-fold selectivity for rat D 3 vs D 2 receptors (Yuan et al, 1998;Newman et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

The Novel Dopamine D3 Receptor Antagonist NGB 2904 Inhibits Cocaine's Rewarding Effects and Cocaine-Induced Reinstatement of Drug-Seeking Behavior in Rats

Newman

Gilbert

et al. 2005

Neuropsychopharmacol

146

177

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Accumulating evidence indicates that dopamine (DA) D 3 receptor antagonists appear highly promising in attenuating cocaine reward and relapse in preclinical models of addiction. In the present study, we investigated the effects of the novel D 3 -selective antagonist NGB 2904 (N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-3-fluorenylcarboxamide) on cocaine self-administration, cocaine-enhanced brain stimulation reward (BSR), and cocaine-triggered reinstatement of drug-seeking behavior in male Long-Evans rats. We found that: (1) acute intraperitoneal (i.p.) administration of NGB 2904 (0.1-10 mg/kg) failed to alter cocaine self-administration (0.5 mg/kg/infusion) under fixed-ratio 2 (FR2) reinforcement, but 1 or 5 mg/kg NGB 2904 significantly lowered the break-point for cocaine self-administration under progressive-ratio (PR) reinforcement; (2) cocaine (1, 2, and 10 mg/kg) significantly enhanced electrical BSR (decreased brain reward thresholds), while NGB 2904 significantly inhibited the enhancement of BSR elicited by 2 mg/kg, but not 10 mg/kg of cocaine; (3) NGB 2904 alone neither maintained self-administration behavior nor altered brain reward thresholds; and (4) NGB 2904 significantly inhibited cocaine-triggered reinstatement of extinguished drug-seeking behavior, but not sucrose-plus-sucrose-cue-triggered reinstatement of sucrose-seeking behavior. Overall, these data show that the novel D 3 -selective antagonist NGB 2904 attenuates cocaine's rewarding effects as assessed by PR self-administration, BSR, and cocaine-triggered reinstatement of cocaine-seeking behavior. Owing to these properties and to its lack of rewarding effects (as assessed by BSR and by substitution during drug self-administration), NGB 2904 merits further investigation as a potential agent for treatment of cocaine addiction.

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The dopamine D3 receptor partial agonist, BP 897, is an antagonist at human dopamine D3 receptors and at rat somatodendritic dopamine D3 receptors

Cited by 73 publications

References 21 publications

Effects of a Dopamine D3 Receptor Ligand, BP 897, on Acquisition and Expression of Food-, Morphine-, and Cocaine-induced Conditioned Place Preference, and Food-seeking Behavior in Rats

Effects of a Dopamine D3 Receptor Ligand, BP 897, on Acquisition and Expression of Food-, Morphine-, and Cocaine-induced Conditioned Place Preference, and Food-seeking Behavior in Rats

The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats

The Novel Dopamine D3 Receptor Antagonist NGB 2904 Inhibits Cocaine's Rewarding Effects and Cocaine-Induced Reinstatement of Drug-Seeking Behavior in Rats

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