The putative dopamine D3 receptor agonist 7-OH-DPAT: lack of mesolimbic selectivity

Liu, June-Chin; Cox, Richard F.; Greif, Gabriela J.; Freedman, Jonathan E.; Waszczak, Barbara L.

doi:10.1016/0014-2999(94)00477-3

Cited by 32 publications

(17 citation statements)

References 29 publications

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“…First, the contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the display of turning behaviour is solely due to its ability to activate dopamine D2 receptors. This conclusion fits in with earlier reports showing that this drug behave similarly to dopamine D2 receptor agonists (Caine et al, 1995;Freedman et al, 1994;Gonzalez and Sibley, 1995;Large and Stubbs, 1994;Liu et al, 1994;Starr and Stair, 1995). The present study, however, shows that this holds also true for intracerebrally administered 7-OH-DPAT, confirming and extending thereby the findings reported in our accompanying paper (Koshikawa et al, 1996b).…”

Section: Discussionsupporting

confidence: 92%

“…Fax: 81 3 3219-8136. Freedman et al, 1994;Liu et al, 1994; behavioural stud ies: Koshikawa et al, 1996b;Large and Stubbs, 1994). Apart from the accompanying paper, in which the effects of intra-accumbens injections of 7-OH-DPAT on jaw movements were studied (Koshikawa et al, 1996b), all remaining studies on the behavioural function of dopamine D3 receptors are limited to studies in which 7-OH-DPAT and other putative, selective dopamine D3 receptor agents are systemically applied.…”

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confidence: 99%

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Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

Koshikawa

Kitamura

Kobayashi

et al. 1996

European Journal of Pharmacology

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The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of turning behaviour in rats. When combined with the dopamine receptor agonist (± )-i-phenyl-2,3,4,5-tetrahydro-1 //-3-benzazepine-7,8-diol (SKF-38393, 5 jx g ) , the putative dopamine D3 receptor agonist (±)-7-hydroxy-/V,N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 jJLg) elicited contralateral turning in a dose-dependent manner following unilateral injection into the shell, but not the core, of the nucleus accumbens. The turning pattern displayed was identical to that reported previously after intra-accumbens administration of the cocktail of SKF-38393 and the dopamine D2 receptor agonist quinpirole. The behaviour under study was dose-dependently attenuated by local administration of the dopamine Dj receptor antagonist /?(-h)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1//-3-benzazepi ne (SCH 23390: 10 and 100 ng), the dopamine D2 receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor antagonist /-sulpiride (5 and 25 ng). Combined blockade of both dopamine Dj and D2 receptors in the shell with a dose of either antagonist alone that produced just a moderate reduction (10 ng SCH 23390 and 50 ng domperidone) completely antagonized the turning behaviour elicited by the cocktail of SKF-38393 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist, 5( + )-(4a/?,10W?)-3,4,4tf,10£~tetrahydro-4-propyl-2tf,5//-[l]benzopyrano [4,[3][4][5][6]907, 10 jxg), in the cocktail did produce no turning behaviour at all. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific turning behaviour: the contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the display of turning behaviour is solely due to its ability to activate dopamine D2 receptors,

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

Koshikawa

Kitamura

Kobayashi

et al. 1996

European Journal of Pharmacology

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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%

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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“…Injections of SCH23390 into the VTA at approximate final concentrations between 6 and 24 M (assuming a 1000-fold dilution) increased cocaine self-administration, suggesting that dendritically released dopamine normally moderates reward behavior through D1 receptor activation. Considering that VTA neurons contain D2-like receptors coupled to GIRK channels (Momiyama et al, 1993;Liu et al, 1994), it is plausible that the SCH23390 actions might reflect the inhibition of D2 receptor-activated GIRK currents and subsequent excitation of VTA neurons.…”

Section: Discussionmentioning

confidence: 99%

Classic D1 Dopamine Receptor AntagonistR-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) Directly Inhibits G Protein-Coupled Inwardly Rectifying Potassium Channels

Kuzhikandathil

Oxford

2002

Mol Pharmacol

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R-(ϩ)-7- 3,4,dro-1H-3-benzazepine hydrochloride (SCH23390) is a widely used, highly selective antagonist of D1 dopamine receptors. While investigating the crosstalk between D1 and D3 dopamine receptor signaling pathways, we discovered that in addition to being a D1 receptor antagonist, SCH23390 and related compounds inhibit G protein-coupled inwardly rectifying potassium (GIRK) channels. We present evidence that SCH23390 blocks endogenous GIRK currents induced by either somatostatin or D3 dopamine receptors in AtT-20 cells (IC 50 , 268 nM). The inhibition is receptor-independent because constitutive GIRK currents in Chinese hamster ovary cells expressing only GIRK channels are also blocked by SCH23390. The inhibition of GIRK channels is somewhat selective because members of the closely related Kir2.0 family of inwardly rectifying potassium channels, as well as various endogenous cationic currents present in AtT-20 cells, are not affected. In addition, in current clamp recordings, SCH23390 can depolarize the membrane potential and induce AtT-20 cells to fire action potentials, indicating potential physiological significance of the GIRK channel inhibition. To identify the chemical features that contribute to GIRK channel block, we tested several structurally related compounds [SKF38393, R-(ϩ)-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (normethyl-SCH23390), and R-(ϩ)-2,3,4,5-tetrahydro-8-iodo-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrochloride (iodo-SCH23390)], and our results indicate that the halide atom is critical for blocking GIRK channels. Taken together, our results suggest that SCH23390 and related compounds might provide the basis for designing novel GIRK channel-selective blockers. Perhaps more importantly, some studies that have exclusively used SCH23390 to probe D1 receptor function or as a diagnostic of D1 receptor involvement may need to be reevaluated in light of these results.We have previously shown that the D3 dopamine receptor couples to and activates G protein-coupled inwardly rectifying potassium (GIRK) channels (Werner et al., 1996;Kuzhikandathil et al., 1998) and inhibits P/Q-type calcium channels (Kuzhikandathil and Oxford, 1999). Given the coexpression of D1 and D3 dopamine receptors in central nervous system neurons, particularly in a subset of nucleus accumbens neurons (Le Moine and Bloch, 1996), we were interested in exploring the functional consequence of D1 receptor activation on D3 receptor-GIRK channel coupling. To address this issue, we used two ligands that are highly selective for D1 receptors and have long served as diagnostic probes of D1 receptor function. One of these ligands, R-(ϩ)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390), is a highly selective antagonist of D1 dopamine receptors with at least a 1000-fold higher affinity for D1 receptors than for D3 receptors (Iorio et al., 1983;Neve and Neve, 1997). SCH23390 is a member of the phenyltetrahydrobenzazepines, a structural class...

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The putative dopamine D3 receptor agonist 7-OH-DPAT: lack of mesolimbic selectivity

Cited by 32 publications

References 29 publications

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

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

Classic D1 Dopamine Receptor AntagonistR-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) Directly Inhibits G Protein-Coupled Inwardly Rectifying Potassium Channels

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