Dopamine D1 antagonist SCH23390 attenuates self-administration of both cocaine and fentanyl in rats

Awasaki, Yasuyuki; Nishida, Nobuyuki; Sasaki, Satoshi; Sato, Shuzo

doi:10.1016/s1382-6689(97)00147-6

Cited by 21 publications

(10 citation statements)

References 28 publications

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“…In the present study, dopamine receptor antagonists may have decreased this motivation, thereby resulting in the observed decreases in drug self-administration (Arnold and Roberts 1997;Cardinal and Everitt 2004). These findings are similar to those of previous studies conducted at the systemic level, which demonstrate that selective dopamine D1 and D2 receptor antagonists attenuated cocaine selfadministration in rats (Awasaki et al 1997;Corrigall and Coen 1991a;Richardson et al 1993). Additionally, these findings are comparable to those of studies conducted at the level of the nucleus accumbens, which demonstrate that dopamine transmission is directly reinforcing in this region (Carlezon et al 1995;Ikemoto et al 1997).…”

Section: Discussionsupporting

confidence: 91%

Cocaine and heroin (‘speedball’) self-administration: the involvement of nucleus accumbens dopamine and μ-opiate, but not δ-opiate receptors

et al. 2005

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Section: Discussionsupporting

confidence: 91%

Cocaine and heroin (‘speedball’) self-administration: the involvement of nucleus accumbens dopamine and μ-opiate, but not δ-opiate receptors

et al. 2005

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“…Thus, if decreased dopamine release is the parsimonious mechanism that underlies reduced methamphetamine‐ and fentanyl‐induced behaviors in Hn1+/− mice, a more pronounced behavioral effect would be expected in response to a psychostimulant compared with an opioid. We should also note that we previously found indirect evidence for modulation of hnRNP H immunohistochemical staining in cultured rat primary neurons in response to D1 but not D2 receptor activation that was reversed by a D1 receptor antagonist 20 ; thus, because our more recent study did not distinguish between the pre‐ and postsynaptic synaptosome, 19 an alteration in postsynaptic D1 receptor signaling in Hn1+/− mice could also comprise a molecular mechanism underlying both psychostimulant and opioid behaviors 59 …”

Section: Discussionmentioning

confidence: 83%

Sex‐dependent effects of anHnrnph1mutation on fentanyl addiction‐relevant behaviors but not antinociception in mice

Bryant

Healy

Ruan

et al. 2020

Genes Brain and Behavior

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Opioid Use Disorder (OUD) and opioid‐related deaths remain a major public health concern in the United States. Both environmental and genetic factors influence risk for OUD. We previously identified Hnrnph1 as a quantitative trait gene underlying the stimulant, rewarding, and reinforcing properties of methamphetamine. Prior work shows that hnRNP H1, the RNA‐binding protein encoded by Hnrnph1, post‐transcriptionally regulates Oprm1 (mu opioid receptor gene)—the primary molecular target for the therapeutic and addictive properties of opioids. Because genetic variants can exert pleiotropic effects on behaviors induced by multiple drugs of abuse, in the current study, we tested the hypothesis that Hnrnph1 mutants would show reduced behavioral sensitivity to the mu opioid receptor agonist fentanyl. Hnrnph1 mutants showed reduced sensitivity to fentanyl‐induced locomotor activity, along with a female‐specific reduction in, and a male‐specific induction of, locomotor sensitization following three, daily injections (0.2 mg/kg, i.p.). Hnrnph1 mutants also required a higher dose of fentanyl to exhibit opioid reward as measured via conditioned place preference (CPP). Male Hnrnph1 mutants showed reduced fentanyl reinforcement. Hnrnph1 mutants also showed reduced sucrose motivation, suggesting a reward deficit. No genotypic differences were observed in baseline thermal nociception, fentanyl‐induced antinociception, physical or negative affective signs of opioid dependence, or in sensorimotor gating. In the context of our prior work, these findings suggest that Hnrnph1 dysfunction exerts a selective role in reducing the addiction liability to drugs of abuse (opioids and psychostimulants), which could provide new biological pathways to improve their therapeutic profiles.

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“…A number of studies have shown that D 1 -or D 2 -preferring antagonists inhibit cocaine self-administration, cocaineenhanced BSR, and cocaine-triggered reinstatement of drug-seeking behavior (Wilson and Schuster, 1972;de Wit and Wise, 1977;Koob et al, 1987;Bergman et al, 1990;Corrigall and Coen, 1991;McGregor and Roberts, 1993;Caine and Koob, 1994;Caine et al, 1995Caine et al, , 2002Self et al, 1996;Awasaki et al, 1997;Ikemoto et al, 1997;Kita et al, 1999;Spealman et al, 1999;Khroyan et al, 2000Khroyan et al, , 2003Hummel and Unterwald, 2002;Norman et al, 2002;Anderson et al, 2003;Sanchez et al, 2003; for reviews see Platt et al, 2002;Kapur and Mamo, 2003;Gorelick et al, 2004). Consequently, this raises the issue of whether the presently observed attenuating effects of NGB 2904 in these three behavioral paradigms might be attributable to D 1 or D 2 receptor-selective antagonism rather than to D 3 receptor-selective antagonism.…”

Section: Ngb 2904's Selective Blockade Of Da D 3 Receptorsmentioning

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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Dopamine D1 antagonist SCH23390 attenuates self-administration of both cocaine and fentanyl in rats

Cited by 21 publications

References 28 publications

Cocaine and heroin (‘speedball’) self-administration: the involvement of nucleus accumbens dopamine and μ-opiate, but not δ-opiate receptors

Cocaine and heroin (‘speedball’) self-administration: the involvement of nucleus accumbens dopamine and μ-opiate, but not δ-opiate receptors

Sex‐dependent effects of anHnrnph1mutation on fentanyl addiction‐relevant behaviors but not antinociception in mice

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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