The novel dopamine D4 receptor agonist (PD 168,077 maleate): Doses with different effects on locomotor activity are without effect in classical conditioning

Nayak, Sahana; Cassaday, Helen J.

doi:10.1016/s0278-5846(03)00031-9

Cited by 27 publications

(17 citation statements)

References 28 publications

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“…One obvious concern that can be raised is whether the dose range of this compound tested herein is adequate or not. Nayak and Cassaday (2003) reported that systemic injection (i.p.) of PD168077 produced a dose-dependent increase in locomotor activity in rats when the dose range was 0.046-1 mg/kg and PD168077 given by the effective doses on locomotor activity had no effect on associative learning tests motivated by either appetitive or aversive stimuli.…”

Section: Discussionmentioning

confidence: 99%

“…Doses of each drug were as follows: SKF38393 (0, 1, and 3 mg/kg), quinpirole (0, 0.01, and 0.03 mg/kg), bromocriptine (0, 1, 2, 4, 8, 16, and 32 mg/kg), and PD168077 (0, 0.5, 1.0, and 3.0 mg/kg). Doses and pretreatment times were referenced via a pilot study in this laboratory and via previous studies examining the effects of systemic injection of these drugs on the conditioned behaviors in the rat (Cory-Slechta et al, 1996;Knapp and Kornestsky, 1994;Koffarnus et al, 2009;Nayak and Cassaday, 2003;Sanger et al, 1996;Weissenborn et al, 1996). The doses used in this study were selected with to the aim of avoiding the appearance of any gross motor deficit or stereotypy behavior in the subject under drug treatment.…”

Section: Drugsmentioning

confidence: 99%

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Differential effects of dopamine receptor subtype-specific agonists with respect to operant behavior maintained on a differential reinforcement of low-rate responding (DRL) schedule

Chiang¹,

Cheng²,

Liao³

2015

Pharmacology Biochemistry and Behavior

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Section: Discussionmentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

Differential effects of dopamine receptor subtype-specific agonists with respect to operant behavior maintained on a differential reinforcement of low-rate responding (DRL) schedule

Chiang¹,

Cheng²,

Liao³

2015

Pharmacology Biochemistry and Behavior

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“…It seems unlikely that the failure of PD 168,077 to induce nicotine-seeking behavior resulted from a low selectivity for DRD4, because the agonist has been demonstrated to be highly selective for DRD4, showing low binding affinities for other dopaminergic, adrenergic, or serotoninergic receptors (eg, with 4100-fold selectivity over DRD1, 4400-fold selectivity over DRD2, and 4300-fold selectivity vs DRD3) (Glase et al, 1997). It also seems unlikely that the failure of PD 168,077 to induce nicotine-seeking behavior resulted from an insufficient dosage as a similar range of doses has been used to elucidate the specific function of DRD4 in in vivo studies (Bernaerts and Tirelli, 2003;Gago et al, 2007;Nayak and Cassaday, 2003). Previously, it was reported that the role of both DRD1 antagonists and agonists in the reinstatement of cocaine-seeking behavior is dissociable in rats: a selective DRD1 antagonist, SCH23390, attenuates, whereas a selective DRD1 agonist has no affect on, the reinstatement of cocaine-seeking behavior in rats (Self, 2004).…”

Section: Discussionmentioning

confidence: 99%

Blockade of Dopamine D4 Receptors Attenuates Reinstatement of Extinguished Nicotine-Seeking Behavior in Rats

Yan

Pushparaj

Strat

et al. 2011

Neuropsychopharmacol

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Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It has been reported that polymorphism of the DRD4 gene in humans is associated with reactivity to cues related to tobacco smoking. However, the role of DRD4 in animal models of nicotine addiction has seldom been explored. In our study, male Long-Evans rats learned to intravenously self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Effects of the selective DRD4 antagonist L-745,870 were evaluated on nicotine self-administration behavior and on reinstatement of extinguished nicotine-seeking behavior induced by nicotine-associated cues or by priming injections of nicotine. L-745,870 was also tested on reinstatement of extinguished food-seeking behavior as a control. In addition, the selective DRD4 agonist PD 168,077 was tested for its ability to reinstate extinguished nicotine-seeking behavior. Finally, L-745,870 was tested in Sprague Dawley rats trained to discriminate administration of 0.4 mg/kg nicotine from vehicle under an FR schedule of food delivery. L-745,870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast, L-745,870 did not affect established nicotine self-administration behavior or reinstatement of food-seeking behavior induced by food cues or food priming. L-745,870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168,077 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745,870 selectively attenuated both cue- and nicotine-induced reinstatement of nicotine-seeking behavior, without affecting cue- or food-induced reinstatement of food-seeking behavior, DRD4 antagonists are potential therapeutic agents against tobacco smoking relapse.

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“…However, the D 4 R agonist (PD168,077) (Glase et al, 1997) and D 4 R antagonist (L745,870) (Kulagowski et al, 1996) used in the present study have been demonstrated to be highly selective for this receptor, showing low binding affinities for other dopaminergic, adrenergic, or serotoninergic receptors. Thus, PD168,077 (Wang et al, 2002(Wang et al, , 2003Azdad et al, 2003;Bernaerts et al, 2003;Nayak et al, 2003) and L745,870 (Bristow et al, 1997;Zhang et al, 2002a;Azdad et al, 2003;Cavas and Navarro, 2006) are being used to elucidate the specific function of D 4 R.…”

Section: Discussionmentioning

confidence: 99%

Dopamine D₄ receptor activation decreases the expression of μ‐opioid receptors in the rat striatum

Gago

Fuxé

Agnati

et al. 2007

J of Comparative Neurology

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The dopaminergic and opioid peptide systems interact in many nuclei of the brain. In the striatum, dopamine/opioid peptide interactions modulate locomotor and motivated behaviors as well as reward, motivational, and tolerance processes in opiate dependence. Dopamine D(4) receptors (D(4) R) and mu-opioid receptors (MOR) are highly concentrated in the striosomes (islands) of the striatum, suggesting the existence of receptor-receptor interactions between them. In the present work we studied the role of D(4) R in modulating MOR expression in the islands by using immunohistochemistry and image analysis. The activation of D(4) R by the agonist PD168,077 (1 mg/kg) decreased MOR immunoreactivity (IR) in the striosomes 6 hours after drug treatment. MOR IR levels had recovered 12 hours later. Treatment with a D(4) R antagonist (L745,870, 1mg/kg) blocked downregulation of MOR IR, showing that the D(4) R agonist effects observed were specific. Furthermore, treatment with the D(2)/D(3) receptor agonist quinpirol (1 mg/kg) and D(2)/D(3) receptor antagonist raclopride (1 mg/kg) had no effect in MOR IR, suggesting that D(4) R is the only D2-like receptor producing an MOR downregulation in the islands. The decreases of MOR IR in the striosomes suggest that D(4) R activation may reduce MOR signaling. Increasing evidence has demonstrated that the islands in the striatum play a critical role in habit acquisition during drug addiction. D(4) R/MOR interactions could be crucial in such processes.

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The novel dopamine D4 receptor agonist (PD 168,077 maleate): Doses with different effects on locomotor activity are without effect in classical conditioning

Cited by 27 publications

References 28 publications

Differential effects of dopamine receptor subtype-specific agonists with respect to operant behavior maintained on a differential reinforcement of low-rate responding (DRL) schedule

Differential effects of dopamine receptor subtype-specific agonists with respect to operant behavior maintained on a differential reinforcement of low-rate responding (DRL) schedule

Blockade of Dopamine D4 Receptors Attenuates Reinstatement of Extinguished Nicotine-Seeking Behavior in Rats

Dopamine D₄ receptor activation decreases the expression of μ‐opioid receptors in the rat striatum

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The novel dopamine D4 receptor agonist (PD 168,077 maleate): Doses with different effects on locomotor activity are without effect in classical conditioning

Cited by 27 publications

References 28 publications

Differential effects of dopamine receptor subtype-specific agonists with respect to operant behavior maintained on a differential reinforcement of low-rate responding (DRL) schedule

Differential effects of dopamine receptor subtype-specific agonists with respect to operant behavior maintained on a differential reinforcement of low-rate responding (DRL) schedule

Blockade of Dopamine D4 Receptors Attenuates Reinstatement of Extinguished Nicotine-Seeking Behavior in Rats

Dopamine D4 receptor activation decreases the expression of μ‐opioid receptors in the rat striatum

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Dopamine D₄ receptor activation decreases the expression of μ‐opioid receptors in the rat striatum