Responsivity and Development of Tolerance to the Motor Impairing Effects of Moderate Doses of Ethanol in Alcohol-Preferring (P) and -Nonpreferring (NP) Rat Lines

Bell, Richard L.; Stewart, Robert B.; Woods, Jennifer; Lumeng, Lawrence; Li, Ting‐Kai; Murphy, James M.; McBride, William J.

doi:10.1097/00000374-200105000-00003

Cited by 23 publications

(35 citation statements)

References 40 publications

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“…Although initial sensitivity to alcohol may be an important factor in determining alcohol intake, at least in some cases the critical factor appears to be the individual organism's innate propensity to find alcohol reinforcing. In agreement, the initial sensitivity to alcohol has also been reported to vary widely among rat lines selectively bred for opposite alcohol preference (Colombo et al 2000;Bell et al 2001;Li et al 2001;for review George 1993).…”

Section: Discussionmentioning

confidence: 65%

Voluntary alcohol intake in two rat lines selectively bred for learned helpless and non-helpless behavior

et al. 2004

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Section: Discussionmentioning

confidence: 65%

Voluntary alcohol intake in two rat lines selectively bred for learned helpless and non-helpless behavior

et al. 2004

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“…Schuckit and colleagues (2001) estimate that approximately 40% of children of alcoholics are relatively insensitive to ethanol while only 10% of children of non-alcoholics have this characteristic. Animal research has investigated whether these initial intrasessional factors are associated with subsequent chronic tolerance development or drug consumption by using rodents from outbred and inbred strains, as well as knock-out mice and selectively bred lines for drug consumption, drug sensitivity, and acute tolerance [e.g., outbred strains (Tabakoff and Culp 1984;San-Marina et al 1989;Khanna et al 1990b;Khanna et al 1991); inbred strains (Crabbe et al 1982;Tabakoff and Culp 1984;Khanna et al 1990a;Crabbe et al 1994;Gehle and Erwin 2000); knock-out mice (Naassila et al 2002); lines selectively bred for consumption (Tampier and Mardones 1999;Tampier et al 2000;Bell et al 2001); lines selectively bred for sensitivity (Khanna et al 1985;Crabbe et al 1989;Limm andCrabbe 1992: Crabbe 1994;Browman et al 2000;Deitrich et al 2000;Draski et al 2001;Palmer et al 2002); lines selectively bred for acute tolerance (Deitrich et al 2000;Rustay et al 2001;Wu et al 2001)]. While the scientific literature is in general agreement that initial sensitivity and acute tolerance are relevant to the subsequent development of chronic tolerance and drug consumption, a coherent description of this relationship has not emerged.…”

Section: Discussionmentioning

confidence: 99%

Individual differences in initial sensitivity and acute tolerance predict patterns of chronic drug tolerance to nitrous-oxide-induced hypothermia in rats

2005

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Rationale: A preventive strategy for drug addiction would benefit from being able to identify vulnerable individuals. Understanding how an individual responds during an initial drug exposure may be useful for predicting how that individual will respond to repeated drug administrations.Objectives: This study investigated whether individual differences in initial drug sensitivity and acute tolerance can predict how chronic tolerance develops.Methods: During an initial 3-h administration of 60% nitrous oxide (N 2 O), male Long-Evans rats were screened for N 2 O's hypothermic effect into subsets based on being initially insensitive (II), sensitive with acute tolerance (AT), or sensitive with no intrasessional recovery (NR). Animals in each individual difference category were randomly assigned to receive six 90-min exposures of either 60% N 2 O or placebo gas. Core temperature was measured telemetrically.Results: Rats that exhibited a comparable degree of hypothermia during an initial N 2 O exposure, but differed in acute tolerance development, developed different patterns of chronic tolerance. Specifically, the NR group did not become fully tolerant over repeated N 2 O exposures while the AT group developed an initial hyperthermia followed by a return of core temperature to control levels indicative of full tolerance development. By the second N 2 O exposure, the II group breathing N 2 O became hyperthermic relative to the placebo control group and this hyperthermia persisted throughout the multiple N 2 O exposures.Conclusions: Individual differences in initial drug sensitivity and acute tolerance development predict different patterns of chronic tolerance. The hypothesis is suggested that individual differences in opponent adaptive responses may mediate this relationship.

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“…One of the 21 differentially expressed genes in the HIPP, ribosomal protein S2, was located within established alcohol QTLs Carr et al, 1998Carr et al, ,2003Foroud et al, 2002Foroud et al, ,2003Radcliffe et al, 2004;Terenina-Rigaldie et al, 2003) (Table 5). Some of these differences in the HIPP between iP and iNP rats may be associated with the differences in the development and/or persistence of tolerance to the motor impairing effects of alcohol observed for the parent lines (Bell et al, 2001;Gatto et al, 1987aGatto et al, ,1987bWaller et al, 1983).…”

Section: Within-region Analysismentioning

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

Self Cite

107

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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.

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Responsivity and Development of Tolerance to the Motor Impairing Effects of Moderate Doses of Ethanol in Alcohol-Preferring (P) and -Nonpreferring (NP) Rat Lines

Cited by 23 publications

References 40 publications

Voluntary alcohol intake in two rat lines selectively bred for learned helpless and non-helpless behavior

Voluntary alcohol intake in two rat lines selectively bred for learned helpless and non-helpless behavior

Individual differences in initial sensitivity and acute tolerance predict patterns of chronic drug tolerance to nitrous-oxide-induced hypothermia in rats

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

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