Alcohol‐Naïve Alcohol‐Preferring (P) Rats Exhibit Higher Local Cerebral Glucose Utilization Than Alcohol‐Nonpreferring (NP) and Wistar Rats

Smith, Daniel G.; Learn, Jennifer E.; McBride, William J.; Lumeng, L.; Li, T K; Murphy, James M.

doi:10.1111/j.1530-0277.2001.tb02352.x

Cited by 16 publications

(12 citation statements)

References 37 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animal studies, human imaging and post-mortem analyses have previously provided evidence that these regions are implicated in alcoholism. [26][27][28] Data for the analysis came from studies of three experimental paradigms. Paradigm 1 29 examined basal level of gene expression in the brains of the alcohol-naïve iP and iNP lines of rats.…”

Section: Internal Lines Of Evidencementioning

confidence: 99%

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Bertsch

Strother

et al. 2006

Pharmacogenomics J

View full text Add to dashboard Cite

We describe a comprehensive translational approach for identifying candidate genes for alcoholism. The approach relies on the cross-matching of animal model brain gene expression data with human genetic linkage data, as well as human tissue data and biological roles data, an approach termed convergent functional genomics. An analysis of three animal model paradigms, based on inbred alcohol-preferring (iP) and alcohol-non-preferring (iNP) rats, and their response to treatments with alcohol, was used. A comprehensive analysis of microarray gene expression data from five key brain regions (frontal cortex, amygdala, caudate-putamen, nucleus accumbens and hippocampus) was carried out. The Bayesian-like integration of multiple independent lines of evidence, each by itself lacking sufficient discriminatory power, led to the identification of high probability candidate genes, pathways and mechanisms for alcoholism. These data reveal that alcohol has pleiotropic effects on multiple systems, which may explain the diverse neuropsychiatric and medical pathology in alcoholism. Some of the pathways identified suggest avenues for pharmacotherapy of alcoholism with existing agents, such as angiotensin-converting enzyme (ACE) inhibitors. Experiments we carried out in alcohol-preferring rats with an ACE inhibitor show a marked modulation of alcohol intake. Other pathways are new potential targets for drug development. The emergent overall picture is that physical and physiological robustness may permit alcohol-preferring individuals to withstand the aversive effects of alcohol. In conjunction with a higher reactivity to its rewarding effects, they may able to ingest enough of this nonspecific drug for a strong hedonic and addictive effect to occur.

show abstract

Section: Internal Lines Of Evidencementioning

confidence: 99%

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Bertsch

Strother

et al. 2006

Pharmacogenomics J

View full text Add to dashboard Cite

show abstract

“…Furthermore, neuropeptide Y (NPY) (Ehlers et al, 1998), corticotropin-releasing factor (Ehlers et al, 1992), neurotensin (Ehlers et al, 1999), substance P, and neurokinin levels (Slawecki et al, 2001) are all significantly lower in CNS regions of P compared to NP rats. Additionally, higher functional neuronal activity has been found in numerous brain regions of the P rat compared to the NP rat (Smith et al, 2001;Strother et al, 2005). Witzmann et al (2003) examined differences in protein levels in the hippocampus (HIPP) and nucleus accumbens (ACB) of alcohol-naïve inbred-P (iP) and inbred-NP (iNP) rats, and found that almost all of the proteins that differed were lower in the iP rats compared to the iNP rats.…”

Section: Introductionmentioning

confidence: 99%

Functional gene expression differences between inbred alcohol-preferring and –non-preferring rats in five brain regions

Kimpel

Strother

McClintick

et al. 2007

Alcohol

107

View full text Add to dashboard Cite

The objective of this study was to determine if there are innate differences in gene expression in selected CNS regions between inbred alcohol-preferring (iP) and -non-preferring (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU), and hippocampus (HIPP) of alcohol-naïve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Using Linear Modeling for Microarray Analysis with a false discovery rate threshold of 0.1, there were 16 genes with differential expression in the ACB, 54 in the AMYG, 8 in the FC, 24 in the CPU, and 21 in the HIPP. When examining the main effect of strain across regions, 296 genes were differentially expressed. Although the relatively small number of genes found significant within individual regions precluded a powerful analysis for over-represented Gene Ontology categories, the much larger list resulting from the main effect of strain analysis produced 17 over-represented categories (P <.05), including axon guidance, gliogenesis, negative regulation of programmed cell death, regulation of programmed cell death, regulation of synapse structure function, and transmission of nerve impulse. Co-citation analysis and graphing of significant genes revealed a network involved in the neuropeptide Y (NPY) transmitter system. Correlation of all significant genes with those located within previously established rat alcohol QTLs revealed that of the total of 313 significant genes, 71 are located within such QTLs. The many regional and overall gene expression differences between the iP and iNP rat lines may contribute to the divergent alcohol drinking phenotypes of these rats.

show abstract

“…Further analysis revealed that the binge ethanol induced changes in sleep-wakefulness in P rats occurred during the dark period on post-ethanol day. There was no significant difference in either wakefulness or sleep (both NREM and REM phases) during the light period, most likely due to different cerebral metabolism rates in P and NP rats (Smith et al, 2001; Strother et al, 2008). Our data is supported by previous animal studies.…”

Section: Discussionmentioning

confidence: 88%

Sleep–wakefulness in alcohol preferring and non-preferring rats following binge alcohol administration

et al. 2010

View full text Add to dashboard Cite

The alcohol-preferring (P) rat is a valid animal model of alcoholism. However, the effect of alcohol on sleep in P or alcohol non-preferring (NP) rats is unknown. Since alcohol consumption has tremendous impact on sleep, the present study compared the effects of binge alcohol administration on sleep-wakefulness in P and NP rats. Using standard surgical procedures, the P and NP rats were bilaterally implanted with sleep recording electrodes. Following post-operative recovery and habituation, pre-ethanol (baseline) sleep-wakefulness was electrographically recorded for 48 hr. Subsequently, ethanol was administered beginning with a priming dose of 5 g/Kg followed by two doses of 2 g/Kg every 8 hrs on the first day and three doses of 3 g/Kg/8 hr on the second day. On the following day (post-ethanol), undisturbed sleep-wakefulness was electrographically recorded for 24 hr. Our initial results suggest that, during baseline conditions, the time spent in each of the three behavioral states: wakefulness, non-rapid eye movement (NREM) sleep and REM sleep, was comparable between P and NP rats. However, the P rats were more susceptible to changes in sleep-wakefulness following 2 days of binge ethanol treatment. As compared to NP rats, the P rats displayed insomnia like symptoms including a significant reduction in the amount of time spent in NREM sleep coupled with a significant increase in wakefulness on post-ethanol day. Subsequent analysis revealed that binge ethanol induced increased wakefulness and reduced NREM sleep in P rats occurred mainly in the dark period. This is the first study that : 1) demonstrates spontaneous sleep-wake profile in P and NP rats, and 2) compares the effects of binge ethanol treatment on sleep in P and NP rats. Our results suggest that as compared to NP rats, the P rats were more susceptible to sleep disruptions after binge ethanol treatment. In addition, the P rats exhibited insomnia-like symptoms observed during abstinence from alcohol in human subjects.

show abstract

Alcohol‐Naïve Alcohol‐Preferring (P) Rats Exhibit Higher Local Cerebral Glucose Utilization Than Alcohol‐Nonpreferring (NP) and Wistar Rats

Cited by 16 publications

References 37 publications

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Functional gene expression differences between inbred alcohol-preferring and –non-preferring rats in five brain regions

Sleep–wakefulness in alcohol preferring and non-preferring rats following binge alcohol administration

Contact Info

Product

Resources

About