Dopamine D2 Receptor Binding, Drd2 Expression and the Number of Dopamine Neurons in the BXD Recombinant Inbred Series: Genetic Relationships to Alcohol and Other Drug Associated Phenotypes

Hitzemann, Robert; Hitzemann, Barbara; Rivera, Seth; Gatley, John; Thanos, Peter K.; Shou, Lu Lu Siming; Williams, Robert W.

doi:10.1097/00000374-200301000-00002

Cited by 19 publications

(22 citation statements)

References 49 publications

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“…Despite enhancing the sensitivity of our measure by testing after two CS+ (ethanol) exposures, we found that dopamine D2-like receptor blockade did not reduce ethanol-induced CPP acquisition. Although these findings agree with studies showing that dopamine D2-like receptors play only a minor role in ethanol reward (e.g., Cunningham et al 1992; Risinger et al 1992), they oppose others that have shown reduced ethanol-induced CPP in D2 receptor-deficient mice (Cunningham et al 2000) and a robust positive correlation between expression of the dopamine D2 receptor gene (Drd2) and ethanol-induced CPP magnitude (Hitzemann et al 2003). …”

Section: Discussionsupporting

confidence: 86%

Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice

Pina

Cunningham

2013

Psychopharmacology

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Rationale Studies support differential roles of dopamine receptor subfamilies in the rewarding and reinforcing properties of drugs of abuse, including ethanol. However, the roles these receptor subfamilies play in ethanol reward are not fully delineated. Objective To examine the roles of dopamine receptor subfamilies in the acquisition of ethanol-induced conditioned place preference (CPP), we pretreated animals systemically with antagonist drugs selective for dopamine D1- (SCH-23390) and D2-like (raclopride) receptors prior to ethanol conditioning trials. Methods Effects of raclopride (0–1.2 mg/kg) and SCH-23390 (0–0.3 mg/kg) on the acquisition of ethanol-induced CPP were examined in DBA/2J mice (experiments 1 and 2). Based on significant effects of SCH-23390, we then determined if SCH-23390 (0.3 mg/kg) produced a place preference on its own (experiment 3). To evaluate whether SCH-23390 impaired learning, we used a conditioned place aversion (CPA) paradigm and pretreated animals with SCH-23390 (0–0.3 mg/kg) before conditioning sessions with LiCl (experiment 4). Results Whereas raclopride (0–1.2 mg/kg) did not affect acquisition, SCH-23390 (0.1–0.3 mg/kg) impaired the development of ethanol-induced CPP. SCH-23390 (0.3 mg/kg) did not produce place preference when tested alone and SCH-23390 (0.1–0.3 mg/kg) did not perturb the acquisition of LiCl-induced CPA. Conclusions Our results support a role for dopamine D1-like but not D2-like receptors in ethanol’s unconditioned rewarding effect as indexed by CPP. Blockade of D1-like receptors did not affect aversive learning in this procedure.

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Section: Discussionsupporting

confidence: 86%

Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice

Pina

Cunningham

2013

Psychopharmacology

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“…For example, the wide variation among individuals in striatal Drd2 expression seen in this study and elsewhere (e.g. Hitzemann et al 2003) is not correlated with the expression of “epigenetic” related genes but has marked behavioral consequences ( Hitzemann et al 1995). Understanding the causes of such variation will be key to developing new therapeutic strategies for the treatment of alcoholism and other drugs of abuse.…”

Section: Discussioncontrasting

confidence: 48%

Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID)

Hitzemann

Oberbeck

Iancu

et al. 2017

Alcohol

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Among animals at risk for excessive ethanol consumption such as the HDID selected lines, there is considerable individual variation in the amount of ethanol consumed and the associated blood ethanol concentrations (BECs). For the HDID lines, this variation occurs even though the residual genetic variation associated with the DID phenotype has been largely exhausted and thus is most likely associated with epigenetic factors. Here we focus on the question of whether the genes associated with individual variation in HDID-1 mice are different from those associated with selection (risk) ( Iancu et al. 2013). Thirty-three HDID-1 mice were phenotyped for their BECs at the end of a standard DID trial, were sacrificed 3 weeks later and RNA-Seq was used to analyze the striatal transcriptome. The data obtained illustrated that there is considerable overlap of the risk and variation gene sets; both focus on the fine tuning of synaptic plasticity.

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“…For example, synaptic trafficking/scaffolding molecules including Syntaxin 12 (Weng, Symons, & Singh, 2009) and Munc18-1 (Fehr et al, 2005) help control ethanol consumption/preference. Additionally, dopamine D2 receptors appear to regulate ethanol reward, as represented by conditioned place preference (Hitzemann et al, 2003). Notably, dependence-enhanced ethanol drinking has not been as extensively studied using recombinant inbred lines.…”

Section: Introductionmentioning

confidence: 99%

Chronic intermittent ethanol inhalation increases ethanol self-administration in both C57BL/6J and DBA/2J mice

McCool

Chappell

2015

Alcohol

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Inbred mouse strains provide significant opportunities to understand the genetic mechanisms controlling ethanol-directed behaviors and neurobiology. They have been specifically employed to understand cellular mechanisms contributing to ethanol consumption, acute intoxication, and sensitivities to chronic effects. However, limited ethanol consumption by some strains has restricted our understanding of clinically relevant endpoints such as dependence-related ethanol intake. Previous work with a novel tastant-substitution procedure using monosodium glutamate (MSG or umami flavor) has shown that the procedure greatly enhances ethanol consumption by mouse strains that express limited drinking phenotypes using other methods. In the current study, we employ this MSG-substitution procedure to examine how ethanol dependence, induced with passive vapor inhalation, modifies ethanol drinking in C57BL/6J and DBA/2J mice. These strains represent ‘high’ and ‘low’ drinking phenotypes, respectively. We found that the MSG substitution greatly facilitates ethanol drinking in both strains, and likewise, ethanol dependence increased ethanol consumption regardless of strain. However, DBA/2J mice exhibited greater sensitivity dependence-enhanced drinking, as represented by consumption behaviors directed at lower ethanol concentrations and relative to baseline intake levels. DBA/2J mice also exhibited significant withdrawal-associated anxiety-like behavior while C57BL/6J mice did not. These findings suggest that the MSG-substitution procedure can be employed to examine dependence-enhanced ethanol consumption across a range of drinking phenotypes, and that C57BL/6J and DBA/2J mice may represent unique neurobehavioral pathways for developing dependence-enhanced ethanol consumption.

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Dopamine D2 Receptor Binding, Drd2 Expression and the Number of Dopamine Neurons in the BXD Recombinant Inbred Series: Genetic Relationships to Alcohol and Other Drug Associated Phenotypes

Cited by 19 publications

References 49 publications

Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice

Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice

Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID)

Chronic intermittent ethanol inhalation increases ethanol self-administration in both C57BL/6J and DBA/2J mice

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