Progress toward a voluntary oral consumption model of alcoholism

Li, T.-K.; Lumeng, Lawrence; McBride, William J.; Waller, M.B.; Hawkins, Tim

doi:10.1016/0376-8716(79)90040-1

Cited by 175 publications

(78 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 59%

“…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: 57%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Nih-pa Author Manuscriptsupporting

confidence: 57%

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

View full text Add to dashboard Cite

show abstract

“…In conclusion, we have developed non-invasive, real-time approaches to track the course of alcohol metabolism in the brain that can be used to characterize differences among animals selectively bred for alcohol consumption behavior (Li et al, 1979), permit safe longitudinal tracking of acute alcohol kinetics during the development and maintenance of the alcohol dependence syndrome (Koob, 2000), and can be extended to humans. With an established model of its brain kinetics, alcohol could also serve as an internal in vivo quantitative reference for spectroscopically visible metabolites.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Quantification of Ethanol Kinetics in Rat Brain

Adalsteinsson

Sullivan

Mayer

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

Proton magnetic resonance spectroscopy was used at 3T to measure the uptake and clearance of brain ethanol in rats after bolus intraperitoneal (i.p.) or intragastric (i.g.) alcohol injection, and to estimate the effects of acute alcohol on brain metabolites. The observation duration was 1-1.5 h with temporal resolution of alcohol sampling ranging from 4 s-4 min. The observed time course of alcohol brain concentration followed a consistent pattern characterized by a rapid absorption, an intermediate distribution, and a slower clearance that approached a linear decay. In a sample of eight healthy Wistar rats, the intercept of the linear clearance term, extrapolated back to the time of injection, correlated well with the administered dose per unit of lean body mass. Alcohol concentration estimation based on spectroscopically measured clearance was compared with blood alcohol levels from blood samples at the end of observation, and were in good agreement with the administered dose. Serial proton spectroscopy measurements provide a valid in vivo method for quantifying brain alcohol uptake and elimination kinetics in real time.

show abstract

“…Using quantitative MRI acquired at 3 and 4.7 T, we observed significant growth in the corpus callosum, cerebellum, and hippocampus of alcohol-naïve adult selectively bred alcohol-preferring (P) rats (Li et al, 1979) over 1-year period during adulthood, from age 88 to 452 days old . Additionally, alcohol consumption by their cohorts, which were amply vitaminized throughout alcohol exposure, attenuated brain growth, particularly of the corpus callosum .…”

Section: Introductionmentioning

confidence: 99%

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Pfefferbaum

Adalsteinsson

Bell

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

Wernicke's encephalopathy (WE) is characterized by lesions in thalamus, hypothalamus (including mammillary nuclei), and inferior colliculi, results in serious disabilities, has an etiology of thiamine deficiency, is treatable with thiamine, and occurs most commonly with alcoholism. Despite decades of study, whether alcohol exposure exacerbates the neuropathology or retards its resolution remains controversial. To examine patterns of brain damage and recovery resulting from thiamine deprivation with and without alcohol exposure, we conducted in vivo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3 T in alcohol-preferring (P) rats, which had voluntarily consumed large amounts of alcohol before thiamine manipulation. A total of 18 adult male P rats (nine alcohol-exposed) received a thiamine-deficient diet for 2 weeks: 10 (five alcohol-exposed) received intraperitoneal (i.p.) pyrithiamine (PT) and eight (four alcohol-exposed) received i.p. thiamine supplementation. Neurological signs developed by day 14. Rats were scanned before thiamine depletion and 18 and 35 days after thiamine repletion. Two-dimensional J-resolved MRS single-voxel spectra with water reference were collected in a voxel subtending the thalamus; metabolite quantification was corrected for voxel tissue content. MRI identified significant enlargement of dorsal ventricles and increase in signal intensities in thalamus, inferior colliculi, and mammillary nuclei of PT compared with thiamine-treated (TT) groups from MRI 1-2, followed by significant normalization from MRI 2-3 in thalamus and colliculi, but not mammillary nuclei and lateral ventricles. Voxel-by-voxel analysis revealed additional hyperintense signal clusters in the dorsal and ventral hippocampus and enlargement of the fourth ventricle. MRS showed a significant decline and then partial recovery in thalamic N-acetylaspartate, a marker of neuronal integrity, in PT compared with TT rats, with no change detected in creatine, choline, or glutamate. PT rats with prior alcohol exposure exhibited attenuated recovery in the thalamus and arrested growth of the corpus callosum; further, two of the five alcohol-exposed PT rats died prematurely. Parenchymal and ventricular changes with thiamine manipulation concur with human radiological signs of WE. The enduring macrostructural and neurochemical abnormalities involving critical nodes of Papez circuit carry liabilities for development of amnesia and incomplete recovery from other cognitive and motor functions subserved by the affected neural systems.

show abstract

Progress toward a voluntary oral consumption model of alcoholism

Cited by 175 publications

References 23 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

In Vivo Quantification of Ethanol Kinetics in Rat Brain

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Contact Info

Product

Resources

About