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Ting-Kai Li

Publications and source records attributed to Ting-Kai Li.

At least 37 records · Page 2Linked to original sources
PubMed2005

The role of acetaldehyde in the central effects of ethanol.

This article represents the proceedings of a symposium at the 2004 annual meeting of the Research Society on Alcoholism in Vancouver, Canada. The symposium was organized by Etienne Quertemont and chaired by Kathleen A. Grant. The presentations were (1) Behavioral stimulant effects of intracranial injections of ethanol and acetaldehyde in rats, by Mercè Correa, Maria N. Arizzi and John D. Salamone; (2) Behavioral characterization of acetaldehyde in mice, by Etienne Quertemont and Sophie Tambour; (3) Role of brain catalase and central formed acetaldehyde in ethanol's behavioral effects, by Carlos M.G. Aragon; (4) Contrasting the reinforcing actions of acetaldehyde and ethanol within the ventral tegmental area (VTA) of alcohol-preferring (P) rats, by William J. McBride, Zachary A. Rodd, Avram Goldstein, Alejandro Zaffaroni and Ting-Kai Li; and (5) Acetaldehyde increases dopaminergic transmission in the limbic system, by Milena Pisano and Marco Diana.

Acetaldehyde↗
PubMed2005

Quantifying the risks associated with exceeding recommended drinking limits.

BACKGROUND: Although daily and weekly drinking limits demonstrate strong sensitivity and specificity in identifying alcohol use disorders (AUDs), there are no descriptive data that present the risks associated with exceeding these limits in a format suitable for presentation to patients, students, and the general public. METHODS: Data collected in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions were used to estimate the risks of past-year DSM-IV alcohol abuse and dependence associated with various frequencies of exceeding daily drinking limits (no more than 4 drinks for men; no more than 3 drinks for women) in a nationally representative sample of 26,946 US drinkers 18 years of age and older. These risks were further categorized by whether weekly drinking limits (no more than 14 drinks for men; no more than 7 drinks for women) were exceeded and by maximum number of drinks consumed in the past year. RESULTS: The prevalence of alcohol dependence with abuse increased in a fairly linear fashion with frequency of exceeding daily drinking limits. The prevalence of dependence alone (no abuse) and abuse alone (no dependence) peaked among persons who exceeded the daily limits twice a week and then leveled off, because individuals became increasingly likely to have both disorders at higher frequencies. Exceeding the weekly limits generally increased the risks of both disorders after accounting for frequency of exceeding the daily limits, but not always to a significant extent. Likewise, maximum quantity of drinks consumed was positively associated with the risks of AUDs even after accounting for frequency of risk drinking. There were few gender differences in the risk of dependence after adjusting for frequency of exceeding daily drinking limits, but the risk of alcohol abuse remained greater among men. CONCLUSIONS: These data provide a useful tool for illustrating the broad range of risk of AUDs associated with exceeding recommended drinking limits, and they support the utility of the daily and weekly drinking limits in predicting AUDs.

Adult↗
PubMed2004

Dopamine and serotonin content in select brain regions of weanling and adult alcohol drinking rat lines.

The objective of the present study was to examine innate differences in the tissue content of dopamine (DA), serotonin (5-HT) and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in five brain regions of weanling and adult alcohol-preferring (P), alcohol-nonpreferring (NP), high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) selected rat lines. Adult male and weanling (postnatal day 25) male rats were killed by decapitation and brains were rapidly dissected for the following regions: olfactory tubercles (OTU), nucleus accumbens (ACB), septum (SEP), anterior cerebral cortex (ACTX) and amygdala (AMYG). Tissue extracts were assayed by HPLC with electrochemical detection. Due to significantly higher content levels in the adults, adult and weanling animals were analyzed separately. Significant differences were found in the ACB and OTU between the adult lines in both DA and 5-HT content, with P and HAD rats having lower levels than NP and LAD rats, respectively. Significant differences in DA content between the weanling lines were also found in the OTU, with P and HAD rats having lower DA levels than NP and LAD rats, respectively. These results confirm previous findings of an association between innate low DA content in select limbic regions and high alcohol drinking behavior.

Age Factors↗
PubMed2004

A pilot study of alcohol exposure and pharmacokinetics in women with or without children with fetal alcohol syndrome.

AIMS: To determine the alcohol exposure and pharmacokinetics of alcohol in a group of women who had given birth to children with FAS, compared with women who had not given birth to FAS children. METHODS: 10 women who had given birth to FAS children (FAS mothers) and 20 Controls were studied to determine how they metabolize alcohol in a single limited-access quasi-experimental session of voluntary consumption of alcohol. They had free choice in the consumption of any amount of their favourite beverage for approximately 2.5 h, but their drinking was terminated if the breath alcohol concentrations (BrAC) exceeded 150 mg%. BrACs was measured during ethanol consumption and for several hours after, for estimation of alcohol exposure and pharmacokinetics. RESULTS: FAS mothers consumed significantly larger amounts of alcohol, and achieved significantly higher peak BrAC levels than Controls. The rate of decline of alcohol from the circulation (beta-60) showed a 2-fold variation across subjects but there was no significant difference between the two groups. CONCLUSIONS: This study did not show any difference in alcohol pharmacokinetics in free-choice drinking by non-pregnant women, who either have given or have never given birth to FAS children. However, mothers of FAS children tend to consume more alcohol per session. Future studies in larger samples will be needed to confirm these findings and to examine drinking patterns and other factors that may increase the risk of FAS in children of women who drink alcohol during pregnancy.

Adolescent↗
PubMed2004

Reduced neuropeptide Y mRNA expression in the central nucleus of amygdala of alcohol preferring (P) rats: its potential involvement in alcohol preference and anxiety.

Levels of neuropeptide Y (NPY) mRNA expression in discrete brain regions of alcohol preferring (P) rats and alcohol nonpreferring (NP) rats were examined using in situ hybridization. NPY mRNA expression was significantly lower in the central nucleus of amygdala (CeA) of P rats than NP rats, whereas no differences were found in the medial or basolateral amygdaloid nuclei. This study suggests that reduced NPY gene expression in the CeA may contribute to differences in alcohol preference and other behavioral differences observed between P and NP rats.

Alcohol Drinking↗
PubMed2004

Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations.

Alcoholism is a complex disease with both genetic and environmental risk factors. To identify genes that affect the risk for alcoholism, we systematically ascertained and carefully assessed individuals in families with multiple alcoholics. Linkage and association analyses suggested that a region of chromosome 4p contained genes affecting a quantitative endophenotype, brain oscillations in the beta frequency range (13-28 Hz), and the risk for alcoholism. To identify the individual genes that affect these phenotypes, we performed linkage disequilibrium analyses of 69 single-nucleotide polymorphism (SNPs) within a cluster of four GABA(A) receptor genes, GABRG1, GABRA2, GABRA4, and GABRB1, at the center of the linked region. GABA(A) receptors mediate important effects of alcohol and also modulate beta frequencies. Thirty-one SNPs in GABRA2, but only 1 of the 20 SNPs in the flanking genes, showed significant association with alcoholism. Twenty-five of the GABRA2 SNPs, but only one of the SNPs in the flanking genes, were associated with the brain oscillations in the beta frequency. The region of strongest association with alcohol dependence extended from intron 3 past the 3' end of GABRA2; all 43 of the consecutive three-SNP haplotypes in this region of GABRA2 were highly significant. A three-SNP haplotype was associated with alcoholism, with P=.000000022. No coding differences were found between the high-risk and low-risk haplotypes, suggesting that the effect is mediated through gene regulation. The very strong association of GABRA2 with both alcohol dependence and the beta frequency of the electroencephalogram, combined with biological evidence for a role of this gene in both phenotypes, suggest that GABRA2 might influence susceptibility to alcohol dependence by modulating the level of neural excitation.

Alcoholism↗
PubMed2004

A genomic scan for habitual smoking in families of alcoholics: common and specific genetic factors in substance dependence.

Smoking is a highly heritable, addictive disorder that commonly co-occurs with alcohol dependence. The purpose of this study is to perform a genomic screen for habitual smoking and comorbid habitual smoking and alcohol dependence in families from the Collaborative Study on the Genetics of Alcoholism (COGA). Subjects were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) to evaluate alcohol dependence and habitual smoking (smoking one pack per day or more for at least 6 months). Sixty seven multi-generational families with 154 independent sibling pairs affected with habitual smoking were genotyped in a screening sample. Analyses on 79 multi-generational families with 173 independent sibling pairs were repeated in a replication sample. Sibpair analyses were performed using ASPEX. Four chromosomal regions in the screening sample had increased allele sharing among sibling pairs for habitual smoking with a LOD score greater than 1 (chromosomes 5, 9, 11, and 21). The highest LOD score was on chromosome 9 (LOD = 2.02; allele sharing 58.9%). Four chromosomal regions also had modest evidence for linkage to the comorbid phenotype habitual smoking and alcohol dependence (chromosomes 1, 2, 11, 15); and the strongest finding was on chromosome 2 (LOD = 3.30; allele sharing 69.1%). Previously identified areas (chromosomes 1 and 7) implicated in the development of alcohol dependence in this same data set did not provide evidence for linkage to habitual smoking in the screening sample. In the replication data set, there continued to be increased allele sharing near peaks identified in the screening sample on chromosomes 2 and 9, but the results were modest. An area on chromosome 7, approximately 60 cM from a location previously identified in linkage analysis with alcohol dependence, had increased allele sharing for the comorbid habitual smoking and alcohol dependence. These data provide evidence of specific genetic regions involved in the development of habitual smoking and not alcohol dependence. Conversely, genetic regions that influence the development of alcohol dependence do not appear to contribute to the development of habitual smoking. Finally, there is also evidence of an area on chromosome 2 that may reflect a common genetic vulnerability locus to both habitual smoking and alcohol dependence.

Adolescent↗
PubMed2004

Effects of concurrent access to a single concentration or multiple concentrations of ethanol on ethanol intake by periadolescent high-alcohol-drinking rats.

The objectives of the current study were to assess the effects of access to different concentrations of ethanol and sex of the animal on ethanol consumption of high-alcohol-drinking (HAD-1 and HAD-2) rats during adolescence [postnatal days (PNDs) 30 through 60]. At the beginning of adolescence (PND 30), the rats were given concurrent access to either a single concentration [15% volume/volume (vol./vol.)] or multiple concentrations [10%, 20%, and 30% (vol./vol.)] of ethanol and water. Analyses of ethanol consumption data revealed significant (P < .025) main effects of line, ethanol condition, and week, and a significant line by sex by ethanol condition by week interaction. For the first week, both male and female HAD-1 and HAD-2 rats consumed more ethanol under the multiple ethanol concentration condition than under the single ethanol concentration condition. However, across the second through fourth weeks, this pattern was seen primarily in male and female HAD-1 rats and to a lesser degree in female HAD-2 rats. In general, female rats consumed more fluids than consumed by male rats, and male rats displayed a higher preference for ethanol over water ratio than observed for their female counterparts. In addition, in comparison with HAD-2 rats, HAD-1 rats drank more ethanol and displayed a higher preference for ethanol ratio. Overall, the current study results indicate that, compared with access to a single concentration (which is used in most studies), concurrent access to multiple concentrations of ethanol produced significantly higher ethanol intakes in periadolescent HAD rats, supporting the suggestion that this ethanol drinking condition would have a greater impact on neuronal development. In addition, although the replicate lines were selectively bred by using the same criteria and foundation stock, the higher ethanol intakes of the HAD-1 line, compared with intakes for the HAD-2 line, seen in the current study support the suggestion that there are some differences in their genetic make-up, affecting ethanol intake, which are expressed during periadolescence.

Aging↗
PubMed2004

Sedative and motor-impairing effects of neuropeptide Y and ethanol in selectively bred P and NP rats.

Past findings suggest a positive association between endogenous neuropeptide Y (NPY) activity and ethanol-induced sedation, and there is evidence for additive effects of administered NPY with sedative-hypnotics. The present investigation examined the effects of intracerebroventricular NPY injection on ethanol-induced sedation and motor impairment in selectively bred alcohol-preferring (P) and -nonpreferring (NP) rats. In Experiment 1, P and NP rats were assessed for loss and recovery of righting reflex (RR) following infusion with either NPY (10.0 microg) or aCSF followed by ethanol injection (2.5 g/kg ip). NPY reduced time to lose RR and increased time to regain RR similarly in P and NP rats. Blood-ethanol levels (BELs) were lower at time of recovery in NPY-treated rats relative to aCSF controls. Thus, NPY enhanced ethanol-induced sedation. In Experiment 2, P and NP rats pretreated with either saline or ethanol (1.0 g/kg ip) were assessed for motor activity following infusion with either NPY (2.5, 5.0, or 10.0 microg) or aCSF. Ethanol alone and NPY alone suppressed motor activity, but there were no additive effects between the two. Taken together, these results provide partial support for past observations of additivity between NPY and drug-induced sedation, and suggest a role for NPY in the neurobehavioral effects of acute ethanol exposure.

Alcohol Drinking↗
PubMed2004

Drug addiction: the neurobiology of behaviour gone awry.

Drug addiction manifests as a compulsive drive to take a drug despite serious adverse consequences. This aberrant behaviour has traditionally been viewed as bad "choices" that are made voluntarily by the addict. However, recent studies have shown that repeated drug use leads to long-lasting changes in the brain that undermine voluntary control. This, combined with new knowledge of how environmental, genetic and developmental factors contribute to addiction, should bring about changes in our approach to the prevention and treatment of addiction.

Animals↗
PubMed2004

Alcohol-related olfactory cues activate the nucleus accumbens and ventral tegmental area in high-risk drinkers: preliminary findings.

BACKGROUND: The mesocorticolimbic dopamine system is implicated in motivation and reward and may be involved in the development of alcoholism. METHODS: We used functional magnetic resonance imaging to study the blood oxygen level-dependent (BOLD) response to alcohol-related olfactory stimuli (AROS; odors of beer and whiskey) and non-alcohol-related olfactory stimuli (NAROS; odors of grass and leather) in 10 high-risk (HR) drinkers (average drinks per week, 19.99; SD, 6.99; all with > or = 2 first- or second-degree alcoholic relatives) and 5 low-risk (LR) social drinking controls (drinks per week, 2.82; SD, 2.87; 1 subject had 1 second-degree alcoholic relative). Data were analyzed with SPM99 and random effects analysis by using regions of interest and corrected cluster statistics (p < 0.05) to focus on the nucleus accumbens (NAc) and ventral tegmental area (VTA). RESULTS: In HR subjects, there was a greater BOLD signal increase in the NAc during AROS than during clean air. BOLD signal increases during AROS were also greater in the NAc than the signal increases induced by NAROS. The AROS signal was significantly greater than the NAROS signal in a small number of voxels in the VTA. Finally, the AROS/NAROS difference signal was larger in HR drinkers in both the NAc and VTA. CONCLUSIONS: Alcoholic olfactory cues may invoke the dopaminergic mesocorticolimbic system to a greater degree than nonalcoholic odors and could be effective tools in exploring the role of the dopamine system in susceptibility to alcoholism.

Adult↗
PubMed2004

Comparison of intracranial self-administration of ethanol within the posterior ventral tegmental area between alcohol-preferring and Wistar rats.

BACKGROUND: A previous study indicated that selectively bred alcohol-preferring (P) rats self-administered ethanol (EtOH) directly into the ventral tegmental area (VTA), whereas the alcohol-nonpreferring line did not. Wistar rats will also self-administer EtOH directly into the posterior VTA. Because Wistar rats also have a low preference for EtOH solutions but self-inject EtOH into the VTA, this study was undertaken to test the hypothesis that there is an association between EtOH preference and sensitivity of the VTA to the reinforcing effects of EtOH. METHODS: Adult P and Wistar rats were assigned to groups that received one of the following concentrations of EtOH: 0, 50, 75, 100, 150, or 200 mg/100 ml. Rats were connected to the microinjection system, placed into two-lever (active and inactive) experimental chambers, and given EtOH for the first four sessions (acquisition), artificial cerebrospinal fluid for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). Responding on the active lever produced a 100-nl injection of the infusate. RESULTS: P rats self-infused 75 to 200 mg/100 ml EtOH and demonstrated lever discrimination, whereas Wistar rats reliably self-infused only 150 and 200 mg/100 ml EtOH. Both P and Wistar rats reduced responding on the active lever when artificial cerebrospinal fluid (aCSF) was substituted for EtOH and reinstated responding in session 7 when EtOH was restored, although P rats demonstrated a very robust enhancement of responding for 100 and 150 mg/100 ml EtOH, and this was not found for Wistar rats. CONCLUSIONS: These results suggest that, compared with Wistar rats, the posterior VTA of P rats was more sensitive to the reinforcing effects of EtOH. Furthermore, the reinstatement data suggest that the posterior VTA of P rats underwent neuronal alterations as a result of prior EtOH exposure and extinction that changed the reinforcing effects of EtOH within this region.

Alcohol Drinking↗
PubMed2004

Glutathione S-transferase 8-8 expression is lower in alcohol-preferring than in alcohol-nonpreferring rats.

OBJECTIVE: A primary focus of alcohol research is to provide novel targets for alcohol treatment by identifying genes that predispose individuals to drink alcohol. Animal models of alcoholism developed by selective breeding are invaluable tools to elucidate both the genetic nature and the underlying biological mechanisms that contribute to alcohol dependence. These selected lines (high alcohol preferring and low alcohol preferring) display phenotypic and genetic differences that can be studied to further our understanding of alcohol preference and related genetic traits. By combining molecular techniques, genetic and physiological factors that underlie the cause of alcoholism can be identified. METHODS: Total gene expression analysis was used to identify genes that are differentially expressed in specific brain regions between alcohol-naive, inbred alcohol-preferring (iP) and -nonpreferring (iNP) rats. Quantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, Western blot, and sequence analysis were used to further characterize rat glutathione S-transferase 8-8 (rGST 8-8). RESULTS: Lower expression of rGST 8-8 mRNA was observed in discrete brain regions of iP compared with iNP animals, and these expression differences were confirmed. To determine additional expression patterns of rGST 8-8, we used in situ hybridization. Rat GST 8-8 was highly expressed in hippocampus, the choroid plexus of the dorsal third ventricle and the lateral ventricle, and ependymal cells along the dorsal third ventricle and the third ventricle. Western blot analysis showed that rGST 8-8 protein levels were lower in the hippocampus and the amygdala of iP compared with iNP. A silent single-nucleotide polymorphism in the coding region and three single-nucleotide polymorphisms in the 3'-UTR were identified in the rGST 8-8 cDNA. CONCLUSION: There is regional variation of rGST 8-8 expression in the brain, at both the mRNA and protein level, and the iP strain has lower innate rGST 8-8 levels than the iNP strain in discrete brain regions.

Alcohol Drinking↗
PubMed2004

Effects of long-term episodic access to ethanol on the expression of an alcohol deprivation effect in low alcohol-consuming rats.

BACKGROUND: The alcohol-preferring (P) and -nonpreferring (NP) and high alcohol-drinking (HAD) and low alcohol-drinking (LAD) rats have been selectively bred for divergent preference for ethanol over water. In addition, both P and HAD rats display an alcohol deprivation effect (ADE). This study was undertaken to test whether the NP, LAD-1, and LAD-2 lines of rats could display an ADE as well. METHOD: Adult female NP, LAD-1, and LAD-2 rats were given concurrent access to multiple concentrations of ethanol [5, 10, 15% (v/v)] and water in an ADE paradigm involving an initial 6 weeks of 24-hr access to ethanol, followed by four cycles of 2 weeks of deprivation from and 2 weeks of re-exposure to ethanol (5, 10, and 15%). A control group had continuous access to the ethanol concentrations (5, 10, and 15%) and water through the end of the fourth re-exposure period. RESULTS: For NP rats, a preference for the highest ethanol concentration (15%) was evident by the end of the fifth week of access (approximately 60% of total ethanol fluid intake). Contrarily, LAD rats did not display a marked preference for any one concentration of ethanol. All three lines displayed an ADE after repeated cycles of re-exposure to ethanol, with the general ranking of intake being LAD-1 > NP > LAD-2 (e.g., for the first day of reinstatement of the third re-exposure cycle, intakes were 6.5, 2.9, and 2.4 g/kg/day compared with baseline values of 3.1, 2.0, and 1.3 g/kg/day for each line, respectively). By the 13th week, rats from all three lines, with a ranking of LAD-1 > NP > LAD-2, were drinking more ethanol (3.3, 2.2, and 2.0 g/kg/day, respectively) compared with their consumption during the first week of access (approximately 1.1 g/kg/day for all three lines). CONCLUSION: These data indicate that access to multiple concentrations of ethanol and exposure to multiple deprivation cycles can partially overcome a genetic predisposition of NP, LAD-1, and LAD-2 rats for low alcohol consumption. In addition, the findings suggest that genetic control of low alcohol consumption in rats is not associated with the inability to display an ADE.

Alcohol Drinking↗
PubMed2003

Moderate alcohol exposure compromises neural tube midline development in prenatal brain.

We previously reported that fetal alcohol treatment compromised the development of the midline raphe and the serotonin neurons contained in it. In this study, we report that the timely development of midline neural tissue during neural tube formation is sensitive to alcohol exposure. Pregnant dams were treated from embryonic day 7 (E7, prior to neurulation) or E8.5 (at neurulation) with the following diets: (a) alcohol (ALC), given as either a 20% or 25% ethanol-derived calorie (EDC) liquid diet, or (b) isocaloric liquid diet pair-fed (PF), or (c) standard rat chow (Chow). Fetal brains from each group were examined on E13, E15, or E18. Neural tube development was compromised as a result of alcohol exposure in the following ways: (1) approximately 60% of embryos at E13 and 20% at E15 showed perforation of the floor plate in the diencephalic vesicle, (2) although completely closed at E13, 70-80% of embryos failed to complete the formation of neural tissue at the roof as the alcohol exposure continued to E15, and (3) 60-80% of embryos show delayed 'occlusion' of the ventral canal by newly formed nestin-positive neuroepithelial cells and S100beta-positive glia in the brainstem of E15. The compromised (incomplete) neural tube midline (cNTM) occurred near the ventricles at E13 and E15, but was later completed at E18. In all cases, the cNTM was accompanied by an enlarged ventricle, and dose-dependent brain weight reduction. The midline of the neural tube at the roof and floor plates is known to mediate timely trophic induction for neural differentiation. Prenatal midline deficits also have the potential to affect the development of midline neurons such as raphe, septal nuclei, and the timely crossing of commissural fibers. The results of the liquid diet alcohol exposure paradigm suggest it is more a model for Alcohol-Related Neurodevelopmental Disorder (ARND) featuring neuropsychiatric disorders than for full-blown fetal alcohol syndrome (FAS) with noticeable facial dysmorphogenesis and gross brain retardation.

Animals↗