Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry

Jones, Byron C.; Tarantino, Lisa M.; Rodriguez, Lawrence A.; Reed, Cheryl; McClearn, Gerald E.; Plomin, Robert; Erwin, V. Gene

doi:10.1097/00008571-199910000-00007

Cited by 73 publications

(78 citation statements)

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“…The phenotypes to which these known QTL were associated could be alternative manifestations of the same fundamental genetic process detected with CART transcript abundance. The QTL Dautb3 (dopamine transporter binding 3), which impacts abundance of the dopamine transporter (DAT) in the caudate-putamen in both sexes maps at 25 cM on Chr 11 (Jones et al, 1999). This is an intriguing QTL as the DAT is one of the main targets for psychostimulant action.…”

Section: Discussionmentioning

confidence: 99%

“…Quantitative trait analysis, using panels of BxD recombinant inbred (RI) mice, continues to be one of the leading methods for the study of genes involved in complex neurobehavioral traits. The BxD series has been used to nominate and map QTL that contribute to a wide variety of complex traits including behavioral, pharmacological, neurochemical and neuroanatomical phenotypes (Erwin et al, 1997;Garlow et al, 2005Garlow et al, , 2006Jones et al, 1999Jones et al, , 2003Gora-Masalak et al, 1991;Belknap et al, 1992;Zhang and Gershenfeld 2003). The major goal of this study is to conduct quantitative trait analysis of CART expression in hypothalamus, by utilizing the BxD series of RI mice.…”

Section: Introductionmentioning

confidence: 99%

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Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice

Boone

Hawks

et al. 2008

Brain Research

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Cocaine-Amphetamine Regulated Transcript (CART) peptides are implicated in a wide range of behaviors including in the reinforcing properties of psychostimulants, feeding and energy balance and stress and anxiety responses. We conducted a complex trait analysis to examine natural variation in the regulation of CART transcript abundance (CARTta) in the hypothalamus. CART transcript abundance was measured in total hypothalamic RNA from 26 BxD recombinant inbred (RI) mouse strains and in the C57BL/6 (B6) and DBA/2J (D2) progenitor strains. The strain distribution pattern for CARTta was continuous across the RI panel, which is consistent with this being a quantitative trait. Marker regression and interval mapping revealed significant quantitative trait loci (QTL) on mouse chromosome 4 (around 58.2cM) and chromosome 11 (between 20-36cM) that influence CARTta and account for 31% of the between strain variance in this phenotype. There are numerous candidate genes and QTL in these chromosomal regions that may indicate shared genetic regulation between CART expression and other neurobiological processes referable to known actions of this neuropeptide.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice

Boone

Hawks

et al. 2008

Brain Research

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“…12. Psychophysiological processes involved in exploratory behavior [Rear2, (44)], cocaine induced activation [Cocia 1, (45)], dopamine receptor binding (Drb5, (46), and alcohol acceptance [Aaq2, (47)] may be relevant to choice-based alcohol consumption (Table 5). Syntaxin binding protein 6 is involved in synaptic vesicle-mediated transport.…”

Section: Discussionmentioning

confidence: 99%

Mapping of QTLs for Oral Alcohol Self-Administration in B6.C and B6.I Quasi-Congenic RQI Strains

et al. 2007

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One strategy to identify neurochemical pathways of addiction is to map the relevant genes. In the present study we used 43 B6.C and 35 B6.I inbred RQI mouse strains, carrying <3% donor genome on C57BL/6ByJ background, for gene mapping. The strains were phenotyped for consumption of alcohol (12% v/v) in a two-bottle-choice paradigm, and genotyped for 396 microsatellite markers. The current mapping study extends our earlier experiment scanning five mouse chromosomes (1) to a whole-genome study, and discusses the differences and limitations. Data were analyzed with composite interval (CIM) and multiple interval (MIM) QTL mapping methods. CIM of B6.C strains detected significant QTLs on chrs. 6 and 12. A suggestive, but not significant, locus was detected in the B6.I strains on chr. 12. The best MIM model for B6.C strains confirmed one QTL on chr. 6 and one QTL on chr. 12., while the MIM model for the B6.I strains confirmed the suggestive locus on chr. 12. Some of the QTLs for alcohol consumption are new, while others confirm previously reported QTLs for alcohol preference, and alcohol acceptance.

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“…The protein kinase C gamma (Prkcc) subunit resides at 2 cM of chromosome 7 and this gene product has been implicated in various neurobehavioral processes including anxiety behaviors, spatial and contextual learning, ethanol consumption and impulsive behaviors (Abeliovich et al, 1993a, b;Bowers et al, 2000;Bowers and Wehner, 2001). There are a number of intriguing genes within the NTta LRS peak on chromosome 9, between 25 and 35 cM including the dopamine 2 receptor structural gene (Drd2) at 28 cM (O'Dowd et al, 1990), hypothermia sensitivity (Hts) which is in response to D2-selective agent quinpirole (Buck et al, 2000), cocaine-related behavior 8 (Cocrb8) at 28 cM, ethanol consumption 3 (Etohc3) at 29 cM (Phillips et al, 1998;Jones et al, 1999), and haloperidol-induced catalepsy 1 (Hpic1) at 35 cM (Patel and Hitzemann, 1999). There are also QTL in this region that impact body weight/composition (abdominal fat weight 4, Afw4, body weight Bwnd2wk6, Bwnd6wk4, Bwnd5wk5) and activity patterns (activity-distance traveled 4, Actd4).…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of the Hypothalamic Neurotensin System

Garlow

Boone

Kinkead

et al. 2005

Neuropsychopharmacol

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This study used B Â D recombinant inbred mice to detect and localize genes that control the hypothalamic neurotensin (NT) system. Abundance of transcripts that encode NT and NT receptors 1, 2, and 3 (NTR1, NTR2, and NTR3) in total hypothalamic RNA was the quantitative trait measured. Analysis of transcript abundance data revealed associations with quantitative trait loci (QTL) for NT transcript abundance (NTta) on chromosome 1, 3, 6, 7, 8, and 9; for NTR1ta on chromosome 3, 8, 12, and X; for NTR2ta on chromosome 2, 4, 9, 10, 12, 13, and 17; for NTR3ta on chromosome 1, 7, 11, and 12. NTta QTL on chromosomes 3, 7, and 8 coincide with QTL previously identified that impact NT peptide content and NTR2ta QTL on chromosome 2 and 12 coincide with genes previously associated with NTR2 receptor abundance. The NTta, NTR1ta, and NTR3ta QTL were not linked to their respective structural genes, but there is a highly significant (po0.001) association for NTR2ta on chromosome 12 that includes the Ntsr2 structural gene. There are areas of potential shared genetic regulation between NTta and NTR3ta on chromosome 1 and 7 and for all three receptors on proximal chromosome 12. The NTta QTL on chromosome 9 includes the dopamine D2 receptor (Drd2) gene and QTL involved in responses to dopaminergic agents (Hts), antipsychotics (Hpic1) and cocaine (Cocrb8), and ethanol (Etohc3). These results further strengthen the hypothesis that the NT system is involved in mediating the actions of antipsychotic agents and drugs of abuse.

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Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry

Cited by 73 publications

References 0 publications

Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice

Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice

Mapping of QTLs for Oral Alcohol Self-Administration in B6.C and B6.I Quasi-Congenic RQI Strains

Genetic Analysis of the Hypothalamic Neurotensin System

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