Chronic ethanol tolerance through free-choice drinking in the P line of alcohol-preferring rats

Gatto, Gregory J.; Murphy, James M.; Waller, M.B.; McBride, William J.; Lumeng, Lawrence; Li, T.-K.

doi:10.1016/0091-3057(87)90021-9

Cited by 86 publications

(32 citation statements)

References 13 publications

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“…Voluntary consumption by P rats of amounts of ethanol similar to those in the present study produce pharmacologically significant blood ethanol levels, ranging from 50 to 200 mg% (Li et al, 1979;Murphy et al, 1986), and these levels of consumption by P rats produce tolerance to the effects of ethanol (Gatto et al, 1987; and perhaps even dependence (Kampov-Polevoy et al, 2000;Waller et al, 1982). Ethanoldependent animals exhibit a long-lasting negative affective state defined partly by elevated anxiety-like behavior (Valdez et al, 2002;Koob and LeMoal, 1997) that may be attributable to decreased NPY levels in the amygdala during ethanol abstinence (Roy & Pandey, 2002).…”

Section: Discussionsupporting

confidence: 58%

“…More specifically, the orexigenic effects of NPY are mediated by the PVN (Stanley et al, 1985), the sedative effects by the posterior hypothalamic nucleus (Naveilhan et al, 2001), and the CeA mediates the suppressive effects of NPY on anxiety-like behavior (Heilig et al, 1993) and possibly ethanol drinking (Pandey et al, 2005); the effects of NPY on most, if not all, of these behaviors is augmented following periods of ethanol abstinence (Gilpin et al, 2005;Rimondini et al, 2005). Therefore, Voluntary consumption by P rats of amounts of ethanol similar to those in the present study produce pharmacologically significant blood ethanol levels, ranging from 50 to 200 mg% (Li et al, 1979;Murphy et al, 1986), and these levels of consumption by P rats produce tolerance to the effects of ethanol (Gatto et al, 1987; and perhaps even dependence (Kampov-Polevoy et al, 2000;Waller et al, 1982). Ethanoldependent animals exhibit a long-lasting negative affective state defined partly by elevated anxiety-like behavior (Valdez et al, 2002;Koob and LeMoal, 1997) that may be attributable to decreased NPY levels in the amygdala during ethanol abstinence (Roy & Pandey, 2002).…”

Section: Nih-pa Author Manuscriptsupporting

confidence: 55%

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Neuropeptide Y administration into the amygdala suppresses ethanol drinking in alcohol-preferring (P) rats following multiple deprivations

Gilpin

Stewart

Badia-Elder

2008

Pharmacology Biochemistry and Behavior

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The present experiment examines the effects of NPY administered into the amygdala on ethanol drinking by alcohol-preferring P rats following long-term continuous ethanol access, with and without multiple periods of imposed ethanol abstinence. P rats had access to 15% (v/v) ethanol and water for 11 weeks followed by 2 weeks of ethanol abstinence, re-exposure to ethanol for 2 weeks, 2 more weeks of ethanol abstinence, and a final ethanol re-exposure. Immediately prior to the second ethanol re-exposure, 4 groups of rats received bilateral infusions NPY (0.25, 0.5, 1.0 μg) or artificial cerebrospinal fluid (aCSF) into the amygdala. Two additional groups were given uninterrupted ethanol access and were infused with a single NPY dose (1.0 μg) or aCSF. The highest NPY dose (1.0 μg) suppressed ethanol intake for 24 hrs in rats with a history of ethanol abstinence (i.e. deprivation) periods, but had no effect in rats with a history of continuous ethanol access. Water and food intakes were not altered. These results suggest that the amygdala mediates the suppressive effects of centrally administered NPY on ethanol drinking, and that NPY may block relapse-like drinking by opposing the anxiogenic effects of ethanol abstinence. KeywordsAlcohol-preferring rats; neuropeptide Y; abstinence; deprivation; anxiety; amygdala; allostasis Dysregulation of brain neuropeptide Y (NPY) systems involved in emotionality may mediate both the negative affective state that defines ethanol abstinence and the negative reinforcing effects of ethanol during relapse drinking (Valdez & Koob, 2004). NPY decreases anxiety-like behavior in rats in multiple behavioral assays (Heilig et al., 1989;1992;Broqua et al., 1995;Britton et al., 1997;Sajdyk et al., 1999Sajdyk et al., , 2008. The anxiolytic effects of NPY appear to be mediated by the central nucleus of the amygdala (CeA; Heilig et al., 1993), although a role has also been suggested for the basolateral nucleus of the amygdala (Sajdyk et al., 1999(Sajdyk et al., , 2008. Since there is a body of evidence suggesting that the CeA is involved in the regulation of both Corresponding Author: Nancy E. Badia-Elder, Department of Psychology, IUPUI, 402 N. Blackford Street, LD 124, Indianapolis, IN 46202, Phone:317-278-1815, Fax:317-274-6756, Email: nbadiael@iupui.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Davis, 1992) and ethanol drinking (McBride, 2002), the focus of this investigation was to examine the effects of NPY infusions into the CeA on ethanol intake. NIH Public AccessThe alcohol-preferring (P) and high alcohol drinking (HAD1) lines of r...

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Section: Discussionsupporting

confidence: 58%

Section: Nih-pa Author Manuscriptsupporting

confidence: 55%

Neuropeptide Y administration into the amygdala suppresses ethanol drinking in alcohol-preferring (P) rats following multiple deprivations

Gilpin

Stewart

Badia-Elder

2008

Pharmacology Biochemistry and Behavior

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“…P rats exhibit functional (Gatto et al, 1987) and metabolic tolerance (Lumeng and Li, 1986) following chronic free-choice drinking. Also, following extended periods of chronic free-choice alcohol drinking, P rats exhibit some signs of physical dependence (Waller et al, 1982), such as increased susceptibility to bicuculline-induced seizures (Kampov-Polevoy et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…P rats also voluntarily drink amounts of alcohol sufficient to achieve blood-alcohol levels (BALs) that are known to be reinforcing in rodents (Li et al, 1979;Lumeng and Li, 1986). Finally, following free-choice alcohol drinking, P rats exhibit both functional (Gatto et al, 1987) and metabolic tolerance (Lumeng and Li, 1986) and, following many weeks of access, they exhibit signs of physical dependence (Kampov-Polevoy et al, 2000;Waller et al, 1982).…”

mentioning

confidence: 99%

Dependence‐Induced Alcohol Drinking by Alcohol‐Preferring (P) Rats and Outbred Wistar Rats

Gilpin

Richardson

Lumeng

et al. 2008

Alcoholism Clin & Exp Res

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Background-Chronic intermittent alcohol vapor exposure and selective breeding procedures have been used separately for many years to model specific aspects of alcohol dependence. The purpose of the present investigation was to combine these 2 approaches by exposing alcoholpreferring (P) rats to chronic intermittent alcohol vapor for extended periods of time and then testing them for operant alcohol responding in parallel with a group of outbred Wistar rats at multiple time points following the termination of vapor exposure.

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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

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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Chronic ethanol tolerance through free-choice drinking in the P line of alcohol-preferring rats

Cited by 86 publications

References 13 publications

Neuropeptide Y administration into the amygdala suppresses ethanol drinking in alcohol-preferring (P) rats following multiple deprivations

Neuropeptide Y administration into the amygdala suppresses ethanol drinking in alcohol-preferring (P) rats following multiple deprivations

Dependence‐Induced Alcohol Drinking by Alcohol‐Preferring (P) Rats and Outbred Wistar Rats

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

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