Lack of Discrimination by Agonists for D2 and D3 Dopamine Receptors

Burris, Kevin D.; Pacheco, Mary A.; Filtz, Theresa M.; Kung, Mei‐Ping; Kung, Hank F.; Molinoff, Perry B.

doi:10.1016/0893-133x(94)00099-l

Cited by 75 publications

(45 citation statements)

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“…Dopamine receptors exhibit differing affinity states for dopamine, termed high-affinity and low-affinity states. The low-affinity K i for dopamine for the cloned rat D3 receptor is in the range of 27-44 nM (Sokoloff et al, 1990(Sokoloff et al, , 1992Levesque et al, 1992;Burris et al, 1995), close to basal extracellular dopamine (3-5 nM (Kalivas and Duffy, 1993;Parsons and Justice, 1992)) and basal synaptic dopamine concentrations ((50 nM (Ross, 1991)). In contrast, the low-affinity state K i 's for D1 and D2 receptors are significantly higher.…”

Section: Discussion 'D3 Dopamine Receptor Hypothesis' Of Sensitizationmentioning

confidence: 74%

“…The disparity in binding affinity between D2 and D3 receptor subtypes is not as great for the high-affinity state receptors. The high-affinity state D3 receptor exhibits approximately seven-fold greater affinity for dopamine than the high-affinity D2 receptor (Burris et al, 1995), while the high-affinity D3 receptor has approximately 60-fold greater affinity for dopamine than the high-affinity state D1 receptor (Seeman, 1999). Because dopamine concentrations are elevated for prolonged periods following stimulant drug administration (Jones et al, 1996a, b;Schad et al, 2002;Zetterstrom et al, 1983), these differing affinities suggest that tolerance would develop differentially for each of these three receptor systems under these conditions, with greatest tolerance of D3 receptor-mediated effects.…”

Section: Discussion 'D3 Dopamine Receptor Hypothesis' Of Sensitizationmentioning

confidence: 99%

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Altered Behavioral Response to Dopamine D3 Receptor Agonists 7-OH-DPAT and PD 128907 Following Repetitive Amphetamine Administration

Richtand

Welge

Levant

et al. 2003

Neuropsychopharmacol

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Behavioral sensitization, the progressive and enduring enhancement of certain behaviors following repetitive drug use, is mediated in part by dopaminergic pathways. Increased locomotor response to drug treatment, a sensitizable behavior, is modulated by an opposing balance of dopamine receptor subtypes, with D1/D2 dopamine receptor stimulation increasing and D3 dopamine receptor activation inhibiting amphetamine-induced locomotion. We hypothesize that tolerance of D3 receptor locomotor inhibition contributes to behavioral sensitization. In order to test the hypothesis that expression of behavioral sensitization results in part from release of D3 receptor-mediated inhibition, thereby resulting in decreased response to D3 receptor agonists, we examined the effect of repetitive amphetamine administration on the behavioral response to the D3 receptor preferring agonists 7-OH-DPAT and PD 128907. D3-selective effects have recently been described for both drugs at a low dose. At 1 week following completion of a repetitive treatment regimen, amphetamine-pretreated rats displayed a decreased response to D3-selective doses of both 7-OH-DPAT and PD 128907, when compared to animals receiving saline pretreatment. Moreover, in addition to the quantitative alteration in response, there was a change in the inter-relation between response to amphetamine and D3 agonist. A highly significant inverse relation between locomotor inhibitory response to PD 128907 and the locomotor-stimulant response to amphetamine was observed prior to amphetamine treatment. In contrast, 10 days following repetitive amphetamine treatment, the relation between response to PD 128907 and amphetamine was not detected. The observed behavioral alteration could not be accounted for by changes in D3 receptor binding in ventral striatum. These findings suggest a persistent release of D3 receptor-mediated inhibitory influence contributes to the expression of behavioral sensitization to amphetamine.

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Section: Discussion 'D3 Dopamine Receptor Hypothesis' Of Sensitizationmentioning

confidence: 74%

Section: Discussion 'D3 Dopamine Receptor Hypothesis' Of Sensitizationmentioning

confidence: 99%

Altered Behavioral Response to Dopamine D3 Receptor Agonists 7-OH-DPAT and PD 128907 Following Repetitive Amphetamine Administration

Richtand

Welge

Levant

et al. 2003

Neuropsychopharmacol

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“…Estimates of the binding selectivity of agonists for D3 over D2 receptors are influenced by whether one compares the high or low affinity states of the receptors (e.g. Burris et al, 1995). In the present study [3H]-spiperone preferentially labelled the low affinity sites at which approximately 600 fold selectivity for D3 receptors was seen.…”

Section: Functional Effects Of (+)-Pd 128907mentioning

confidence: 73%

Antagonism of the effects of (+)‐PD 128907 on midbrain dopamine neurones in rat brain slices by a selective D₂ receptor antagonist L‐741,626

Bowery

Razzaque

Emms

et al. 1996

British J Pharmacology

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3 (+)-PD 128907 inhibited cell firing in both the ventral tegmental area and substantia nigra pars compacta with EC50 values of 33 nM (pEC5o= 7.48+0.10, n = 10) and 38 nM (pEC50= 7.42+0.15, n = 5), respectively. No effects of (+)-PD 128907 (100 nM) were observed on glutamate or GABA-mediated synaptic potentials elicited by focal bipolar stimulation. 4 L-741,626 antagonized these effects of (+ )-PD 128907 in a concentration-dependent and surmountable manner with an affinity, determined from Schild analysis, of 20 nM (pKB= 7.71 + 0.14)in the ventral tegmental area and 11 nM (pKB = 7.95 + 0.18) in the substantia nigra pars compacta.5 (+)-PD128907 also inhibited dopamine release in the caudate-putamen with an ECso of 66 nM (n = 5). The affinity of L-741,626 for these nerve terminal autoreceptors (pKB= 7.71 + 0.06; = 20 nM) was identical to that observed on midbrain dopamine neurones. 6 These data demonstrate that the D3 receptor ligand (+)-PD 128907 is a potent agonist on rat midbrain dopamine neurones. However, its lack of regional selectivity, and the high affinity of the selective D2 receptor antagonist L-741,626 for receptors activated by (+ )-PD 128907, was more consistent with an action on D2 autoreceptors rather than upon a D3 dopamine receptor subtype.

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“…[175]). For example, the observed D 3 selectivity of several DA agonists may directly result from the use of in vitro conditions that disfavor the high-affinity conformation of the D 2 receptor such as the inclusion of Na + in some in vitro assay systems [40,180] [20,114,250] as well as labeling of σ [250,296] and 5-HT 1A receptors [72,198] Fig. 1 for further details).…”

Section: In Vitro Pharmacological Characterization Of Da D 3 Ligandsmentioning

confidence: 99%

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

Heidbreder

Gardner

et al. 2005

Brain Research Reviews

304

249

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The cDNA for the dopamine D 3 receptor was isolated and characterized in 1990. Subsequent studies have indicated that D 3 receptors, as well as D 3 receptor mRNA, are primarily localized in limbic regions in mammals. This finding led to the postulate that D 3 receptors may be involved in drug dependence and addiction. However, this hypothesis has been difficult to test due to the lack of compounds with high selectivity for central D 3 receptors. The interpretation of results from studies using mixed D 2 /D 3 agonists and/or antagonists is problematic because these agents have low selectivity for D 3 over D 2 receptors and it is likely that their actions are primarily related to D 2 receptor antagonism and possibly interaction with other neurotransmitter receptors. Currently, with the synthesis and characterization of new highly selective D 3 receptor antagonists such as SB-277011-A this difficulty has been surmounted. The purpose of the present article is to review, for the first time, the effects of various putative D 3 receptor selective compounds in animal models of drug dependence and addiction. The results obtained with highly selective D 3 receptor antagonists such as SB-277011-A, SB-414796, and NGB-2904 indicate that central D 3 receptors may play an important role in drug-induced reward, drug-taking, and cue-, drug-, and stressinduced reinstatement of drug-seeking behavior. Provided these results can be extrapolated to human drug addicts, they suggest that selective DA D 3 receptor antagonists may prove effective as potential pharmacotherapeutic agents to manage drug dependence and addiction.

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Lack of Discrimination by Agonists for D2 and D3 Dopamine Receptors

Abstract: The D2 subtype of dopamine receptor is thought to be an important site of action for antipsychotic drugs (Creese et al. 1976;Seeman et al. 1976). Recently, two new D2-like receptor subtypes, termed D3 and D4

Cited by 75 publications

References 39 publications

Altered Behavioral Response to Dopamine D3 Receptor Agonists 7-OH-DPAT and PD 128907 Following Repetitive Amphetamine Administration

Altered Behavioral Response to Dopamine D3 Receptor Agonists 7-OH-DPAT and PD 128907 Following Repetitive Amphetamine Administration

Antagonism of the effects of (+)‐PD 128907 on midbrain dopamine neurones in rat brain slices by a selective D₂ receptor antagonist L‐741,626

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

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Lack of Discrimination by Agonists for D2 and D3 Dopamine Receptors

Abstract: The D2 subtype of dopamine receptor is thought to be an important site of action for antipsychotic drugs (Creese et al. 1976;Seeman et al. 1976). Recently, two new D2-like receptor subtypes, termed D3 and D4

Cited by 75 publications

References 39 publications

Altered Behavioral Response to Dopamine D3 Receptor Agonists 7-OH-DPAT and PD 128907 Following Repetitive Amphetamine Administration

Altered Behavioral Response to Dopamine D3 Receptor Agonists 7-OH-DPAT and PD 128907 Following Repetitive Amphetamine Administration

Antagonism of the effects of (+)‐PD 128907 on midbrain dopamine neurones in rat brain slices by a selective D2 receptor antagonist L‐741,626

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

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Product

Resources

About

Antagonism of the effects of (+)‐PD 128907 on midbrain dopamine neurones in rat brain slices by a selective D₂ receptor antagonist L‐741,626