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Ting-Kai Li

Publications and source records attributed to Ting-Kai Li.

At least 73 records · Page 4Linked to original sources

Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus.

Human brain oscillations represent important features of information processing and are highly heritable. A common feature of beta oscillations (13-28 Hz) is the critical involvement of networks of inhibitory interneurons as pacemakers, gated by gamma-aminobutyric acid type A (GABA(A)) action. Advances in molecular and statistical genetics permit examination of quantitative traits such as the beta frequency of the human electroencephalogram in conjunction with DNA markers. We report a significant linkage and linkage disequilibrium between beta frequency and a set of GABA(A) receptor genes. Uncovering the genes influencing brain oscillations provides a better understanding of the neural function involved in information processing.

Adolescent↗

The reinforcing effects of acetaldehyde in the posterior ventral tegmental area of alcohol-preferring rats.

Acetaldehyde (ACD), the first metabolite of ethanol, is a biologically active compound, which may mediate some of the reinforcing, behavioral and neurotoxic effects of ethanol. The objective of this study was to test the hypothesis that ACD is reinforcing within the mesolimbic system. The intracranial self-administration (ICSA) technique was employed to determine whether ACD was reinforcing in the posterior ventral tegmental area (VTA), a site that supports the reinforcing actions of ethanol. Adult female alcohol-preferring (P) rats were implanted with guide cannulae aimed at the posterior VTA. Subjects were placed in two-lever operant chambers 7-10 days after surgery. Responding on the "active lever" on a fixed ratio 1 (FR1) schedule of reinforcement caused the delivery of 100 nl of infusate, whereas responses on the "inactive lever" were without consequences. Rats were assigned to one of five groups that self-administered either artificial cerebrospinal fluid (aCSF) throughout all eight sessions (4 h in duration) or 3- and 6-, 11- and 23-, 45- and 90- or 180- and 360-microM ACD for the eight sessions, with the lower concentration of ACD given for the initial four sessions and the higher concentration of ACD given for the last four sessions. A second experiment examined the acquisition (first four sessions), extinction (aCSF in sessions 5 and 6) and reinstatement using 90-microM ACD. A third experiment examined the effects of extending the time-out period (from 5 to 55 s) on the number and pattern of infusions of 23-microM ACD. Adult P rats readily self-administered 6-90-microM ACD and discriminated between the active and inactive levers. Furthermore, rats self-administering 90-microM ACD also demonstrated extinction behavior when aCSF was substituted for ACD and gradually reinstated active lever responding when ACD was reintroduced. P rats maintained similar numbers of infusions and infusion patterns under both time-out schedules. Overall, the data indicate that ACD is a potent reinforcer within the posterior VTA of the P rat.

Acetaldehyde↗

Local cerebral glucose utilization after relapse in ethanol drinking in alcohol-preferring (P) rats.

The [(14)C]-2-deoxyglucose ([(14)C]-2-DG) quantitative autoradiographic technique was used to determine rates of local cerebral glucose utilization (LCGU) in discrete brain regions of adult, male alcohol-preferring (P) rats after 2 weeks of ethanol deprivation (E-D), 3 and 14 days of ethanol-relapse drinking (E-R3; E-R14), and in P rats, which were chronically drinking ethanol (E-C) for 8 weeks during daily 3-h scheduled-access sessions to 15% (vol./vol.) ethanol and water, or were ethanol-naive (E-N). The hypothesis to be tested was that ethanol-relapse drinking is initiated to restore changes in functional activity back to their chronic ethanol-exposed state. The LCGU rates were measured 1 h before the scheduled-access session. Mean ethanol intake did not differ among the groups. The LCGU rates were decreased in 41 of 57 regions or subregions examined in E-C rats compared with findings for E-N rats, including subregions of the cerebral cortex, hippocampus, and structures in the mesocorticolimbic and nigrostriatal systems. After 2 weeks of deprivation, LCGU values tended to return toward control values (E-N) in most CNS regions and did not differ significantly from control values in 12 regions or subregions (e.g., parts of the limbic system, cerebral cortex). Compared with LCGU values that recovered toward control levels in the E-D group, ethanol-relapse drinking was associated with decreased LCGU values in (1) 4 of 10 limbic structures, (2) all 6 cerebral cortical regions, (3) 1 of 4 basal ganglia regions, (4) 2 of 7 hippocampus subregions, and (5) 1 of 6 thalamic nuclei. The present results indicate that ethanol-relapse drinking was associated with reduced LCGU rates in most CNS regions that recovered toward control values and suggested to us that ethanol-relapse drinking may be initiated to restore neuronal function to its prior chronic ethanol-exposure state.

Alcohol Drinking↗

Maintaining steady state arterial alcohol levels in rats by using a physiologically based pharmacokinetic model.

An intravenous method of alcohol administration that maintains arterial alcohol concentrations (AACs) in rats at a prescribed level for a prolonged period was previously described. This method produced steady state AACs between 30 and 180 min after the start of the infusion, but it resulted in substantial overshoots in AAC initially. The present study was designed to achieve target AACs close to steady state more quickly while minimizing any overshoot. A physiologically based pharmacokinetic (PBPK) model of alcohol distribution and elimination was developed for male Wistar rats. Body weight was used to compute individualized infusion rate profiles that would achieve steady state AACs of 75, 150, and 250 mg%. Rats were chronically implanted with cannulae in the jugular vein (for alcohol infusion) and carotid artery (for blood sampling). Alcohol was administered according to the individualized infusion rate profiles. Blood was collected at intervals for AAC determination. The PBPK model-based infusion profiles achieved target AACs 5 min after the start of the infusion and maintained the AACs for 2 h. The AACs deviated an average of 4.9%, 5.1%, and 5.9% from target at the 75, 150, and 250 mg% levels, respectively. Through the application of a PBPK model, it is possible to achieve target AACs close to steady state more quickly in male Wistar rats and to minimize any overshoot in AAC. The PBPK model-based method seems to be improved over the earlier method. Maintaining steady state AACs in rats is useful for studies in which fluctuating alcohol levels may confound experimental results.

Animals↗

Phenotypic and genotypic characterization of the Indiana University rat lines selectively bred for high and low alcohol preference.

The Indiana lines of selected rats, the HAD and LAD replicates and the P and NP lines, were bred for high and low alcohol preference. The P and HAD lines have met criteria for an animal model of alcoholism in that they voluntarily consume sufficient ethanol to achieve significant blood alcohol concentrations, and their alcohol-seeking behavior is reinforced by the pharmacological effects of ethanol rather than its taste, caloric content, or other properties. These lines have been characterized extensively for associated behavioral and physiological phenotypes. The P and HAD rats show an enhanced responsiveness to the stimulatory effects of ethanol and reduced sensitivity to the aversive sedative effects of ethanol. Consistent findings with the selected lines include differences in the mesolimbic dopamine reward system, as well as differences in serotonin, GABA, endogenous opioid, and neuropeptide Y systems. Genetic mapping studies have identified quantitative trait loci influencing alcohol preference on chromosomes 3, 4, and 8 in the inbred P/NP rats and on chromosomes 5, 10, 12, and 16 in the noninbred HAD1/LAD1 rats. The elucidation of the genotypes and phenotypes that result in excessive alcohol intake may lead to a better understanding of alcohol abuse and alcoholism and could guide strategies for potential treatment and prevention.

Alcohol Drinking↗

Deviations in brain early serotonergic development as a result of fetal alcohol exposure.

Serotonin (5-HT) has specific roles not only as a transmitter but also as a signal for differentiation. We recently found that alcohol drinking during pregnancy resulted in incomplete-neural-tube-fusion which hindered the development of midline cells such as 5-HT neurons in mice. We now report that, at the birth of 5-HT neurons (E11), the 5-HT immunoreative (5-HT-im) neurons are often found missing medial projecting fibers towards ventricle in the Alcohol treated group (ALC) as compared with pair-fed (PF) and Chow-fed groups (Chow) in mice. At E13, there are fewer 5-HT-im neurons in either dorsal or median raphe of ALC as compared with PF or Chow; furthermore, neurite outgrowth and migration of the 5-HT neurons are also compromised with alcohol exposure. We, thus, demonstrated that fetal alcohol exposure compromised 5-HT development as early as at the 5-HT neuron birth. Since 5-HT is a signal for development of many forebrain neurons, the deviation of 5-HT in early life may have consequences on brain development that extend beyond those seen in the 5-HT system.

Journal Article↗

Heart rate and motor-activating effects of orally self-administered ethanol in alcohol-preferring (P) rats.

BACKGROUND: Autonomic and behavioral arousals often accompany reinforcement. Additionally, contextual cues associated with alcohol consumption elicit increases in heart rate in alcoholics. This study examined changes in heart rate (HR) and motor activity before and during limited-access to ethanol, saccharin, or water in adult male alcohol-preferring (P) rats. METHODS: Adult male P rats were implanted with radiotelemetric transmitters to measure HR and motor activity. The experiment involved placing the animals in a test chamber for a 90-min pretest period, with water available. Thereafter, the animals were given a 90-min test session with access to one of three test solutions: water, 0.0125% saccharin, or 15% (v/v) ethanol (EtOH). After a week of habituation (water served as the test solution for all three groups), the animals were given their respective test solution for 3 weeks. RESULTS: Analyses of HR revealed that the saccharin and EtOH groups had significantly higher HR than the water group during the pretest period of the third test week. Both the saccharin and EtOH groups had significantly higher HR than the water group during the test period of all three test weeks. Analyses of motor activity revealed that the EtOH group displayed higher motor activity than the water and saccharin groups during the pretest period of the third test week. CONCLUSIONS: The data indicate that oral self-administration of EtOH enhances behavioral and autonomic activation, compared with saccharin or water, in adult male P rats and support previous observations that changes in HR can be used as an index of reinforcement. Additionally, it seems that the behavioral and autonomic activation elicited by EtOH self-administration can be conditioned to the environment in which EtOH was self-administered. These findings parallel reports on cued reactivity (behavioral and autonomic activation) in alcoholics exposed to alcohol-associated stimuli.

Administration, Oral↗

Alcohol dependence symptoms and alcohol dehydrogenase 2 polymorphism: Israeli Ashkenazis, Sephardics, and recent Russian immigrants.

BACKGROUND: Jews have lower rates of alcohol-related problems than other Caucasians. The ADH2*2 allele of the alcohol dehydrogenase 2 (ADH2 ) gene protects against alcoholism in Asians and is found in approximately 20% of Jews. We studied the relationship of ADH2*2 to DSM-IV dependence severity in a random community sample of Israeli Ashkenazis, recent Russian immigrants (also Ashkenazis), and Sephardics. METHODS: Subjects participated in a structured interview that included highly reliable questions on DSM-IV alcohol dependence symptoms. ADH2 genotype was determined for 68 subjects. RESULTS: Recent Russian immigrants had more past and lifetime DSM-IV dependence symptoms. Sephardics had a higher prevalence of ADH2*2 than Ashkenazis. Controlling for group and other potentially confounding factors, ADH2*2 was associated with a lower lifetime DSM-IV alcohol dependence severity, although this differed somewhat within groups. CONCLUSIONS: ADH2*2 protects against dependence severity in Jewish samples. Future work in larger samples should address genetic and environmental factors that affect the relationship of ADH2*2 to alcohol consumption and dependence.

Adult↗

Saccadic eye movements are associated with a family history of alcoholism at baseline and after exposure to alcohol.

OBJECTIVE: To evaluate the influence of family history of alcoholism (FHA) on the response of saccadic eye movements to alcohol. METHOD: Saccadic performance was evaluated in 54 healthy adult subjects with a FHA (family history-positive) and 49 controls (family history-negative). Alcohol and placebo sessions were presented in counterbalanced order. Alcohol was administered intravenously to achieve and maintain a target breath alcohol concentration of 60 mg/100 ml (60%) for 160 min in each subject. During each session, saccadic eye movement testing was performed at baseline (before infusion of alcohol) and twice during the steady-state target breath alcohol concentration. The saccadic testing elicited visually guided saccades (VGS) and antisaccades (AS). Saccadic latency and velocity and the percentage of AS errors were quantified and analyzed using multivariate analysis of variance. RESULTS: The family history-positive and family history-negative groups showed an overall difference at baseline in AS and VGS latencies and velocities in the alcohol and placebo sessions ( p= 0.006). Alcohol delayed saccades such that AS and VGS latencies increased (p = 0.0001) and slowed the execution of saccades such that peak velocities decreased ( p = 0.0002). The percentage of AS errors decreased after alcohol administration, but no significant effect of alcohol (alcohol versus placebo session) was observed (p = 0.1). Latency of AS saccades demonstrated a significant overall FHA effect (p = 0.02) and a significant interaction between FHA and response to alcohol over time (p = 0.02). CONCLUSIONS: Differences in operational characteristics of the saccadic control system are associated with FHA in adult social drinkers, both at baseline and when the brain is exposed to ethanol at 60 mg/100 ml.

Adult↗

Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: I. Periadolescent exposure.

BACKGROUND: The current study examined the effects of ethanol (EtOH) drinking during periadolescence on the subsequent acquisition and extinction of operant self-administration of EtOH and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats to test the hypothesis that alcohol drinking during periadolescence produces enduring alterations that enhance the reinforcing properties of EtOH. METHODS: Periadolescent female P rats were given 24 hr free-choice access to 15% (v/v) EtOH starting at postnatal day (PND) 30 and ending on PND 60 or were similarly housed and received water only. On PND 75, without any prior training, periadolescent alcohol-drinking and periadolescent alcohol-naïve rats were placed in standard two-lever (15% EtOH and water) chambers to examine acquisition of EtOH self-administration with a fixed ratio (FR) 1 schedule of reinforcement. After the acquisition phase and after stable responding was established on an FR5 for EtOH and FR1 for water, P rats underwent extinction training for both EtOH and water rewards. After extinction training and a 2 week home cage period, rats were returned to the operant chambers in the absence of reward for seven consecutive sessions (Pavlovian spontaneous recovery). After this testing period, animals were maintained in their home cage for a week before being returned to the operant chambers and allowed to respond for EtOH and water (reacquisition). RESULTS: Compared with periadolescent alcohol-naïve rats, periadolescent alcohol-drinking rats acquired EtOH responding sooner (i.e., in the first acquisition session), displayed a greater resistance to extinguish EtOH responding (i.e., higher levels of responding in sessions 4-6), had higher responding for more sessions on the EtOH lever in the absence of reward after a prolonged home cage rest period, and had a more prolonged elevated level of EtOH responding during reacquisition (four sessions versus one session). CONCLUSIONS: Overall, the results suggest that periadolescent EtOH drinking by P rats produced long-lasting alterations in the reinforcing effects of alcohol, which increased the likelihood that alcohol drinking would be initiated in adulthood, decreased the likelihood that once adult alcohol drinking began it could be extinguished easily, and increased the potential for relapse.

Aging↗

Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: II. Adult exposure.

BACKGROUND: In a preceding study, we reported that ethanol (EtOH) consumption during periadolescence in alcohol-preferring (P) rats produced significant effects on the acquisition, extinction, Pavlovian spontaneous recovery (PSR), and reacquisition of operant self-administration of EtOH. The objective of the present study was to determine if EtOH consumption during adulthood produced similar effects on subsequent operant behaviors. METHODS: Adult female P rats (>135 days of age) were given 24 hr free-choice access to 15% EtOH for 30 days or were similarly housed and received water only. After a 15 day period of no EtOH access and without any prior training, adult alcohol drinking and adult alcohol-naïve rats were placed in standard two-lever (15% EtOH and water) chambers to examine acquisition of EtOH self-administration. After stable responding was established on a concurrent fixed ratio (FR) 5 FR1 schedule for EtOH versus water, the P rats underwent extinction training for nine sessions. After extinction and a 2 week home cage period (with no operant sessions or access to EtOH), rats were returned to the operant chambers in the absence of reward for seven consecutive sessions to test for PSR. After PSR testing, animals were maintained in their home cage for a week, before being reintroduced to the operant chambers and allowed to respond for EtOH and water. RESULTS: Both the adult alcohol-drinking and adult alcohol-naïve groups rapidly acquired EtOH self-administration, expressed a pronounced PSR, which was augmented by EtOH priming and the presence of a discriminative stimulus (odor cue), and increased responding when EtOH was reinstated. Adult pre-exposure to EtOH did not alter any of the operant measures. CONCLUSIONS: The results of this study suggest that, unlike the results with EtOH pre-exposure during periadolescence, chronic alcohol drinking by P rats in adulthood did not produce sufficient long-lasting changes in neuronal function to alter subsequent operant acquisition of alcohol self-administration, alcohol relapse, or alcohol-seeking behavior.

Aging↗

Binge drinking in Jewish and non-Jewish white college students.

BACKGROUND: In the United States, religious commitment, as measured by service attendance, has an inverse relationship with alcohol consumption, heavy use, and problem use. This association, however, has not been found consistently in Jewish Americans. The present study examined the relationship between religious variables and binge drinking in Jewish and non-Jewish white college students. In addition, the association among genetic, cultural, and religious variables and binge drinking was examined in the Jewish sample alone. METHODS: Participants were 132 Jewish and 147 non-Jewish white college students. All participants completed the Time-Line Follow-Back, had blood drawn for genotyping at the alcohol dehydrogenase locus ADH2, and reported their religious affiliation and the number of religious services attended in the past year. Jewish subjects also completed the Jewish Identity Scale. RESULTS: As hypothesized, more frequent religious service attendance related to lower rates of binge drinking in non-Jews but was not related to binge drinking in Jews. Within the Jewish sample, individuals who were religiously affiliated had approximately one third the risk of binge drinking as those who were secularly affiliated, but identification with Jewish culture was not related to binge drinking. In the total sample, individuals who possessed a variant alcohol dehydrogenase allele ADH2*2 were approximately half as likely to binge drink as those who did not possess this allele. CONCLUSIONS: These results are consistent with previous studies that find an inverse relationship between religious service attendance and heavy alcohol use in Christian but not Jewish college students. Findings within the Jewish sample support theories that suggest religious, not just cultural, Jewish affiliation relates to lower levels of alcohol behavior. More research is needed to identify additional factors, including other religious, cultural, genetic, and biological influences, that protect Jewish Americans from heavy drinking.

Adult↗

Cocaine is self-administered into the shell but not the core of the nucleus accumbens of Wistar rats.

The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine system. However, the possibility that the rewarding properties of cocaine are mediated by direct activation of this system has yielded contradictory findings. The intracranial self-administration technique is used to identify specific brain regions involved in the initiation of response-contingent behaviors for the delivery of a reinforcer. The present study assessed whether adult Wistar rats would self-administer cocaine directly into the nucleus accumbens shell (AcbSh) and core (AcbC). For each subregion, subjects were placed in standard two-lever operant chambers and randomly assigned to one of five groups for each site that were given either artificial cerebrospinal fluid (aCSF), or 400, 800, 1200, or 1600 pmol of cocaine/100 nl to self-administer. The data indicate that rats with placements within the AcbSh readily self-administered 800 to 1600 pmol of cocaine/100 nl and responded significantly more on the active than inactive lever. These subjects also decreased responding on the active lever when aCSF was substituted for cocaine and reinstated responding on the active lever when cocaine was reintroduced. Coinfusion of the D2-like receptor antagonist sulpiride inhibited cocaine self-infusion in the AcbSh. In contrast to the AcbSh data, rats failed to self-administer any tested dose of cocaine into the AcbC or areas ventral to the AcbSh. These findings suggest that the AcbSh is a neuroanatomical substrate for the reinforcing effects of cocaine and that activation of D2-like receptors is involved.

Animals↗

Alcohol and ADH2 in Israel: Ashkenazis, Sephardics, and recent Russian immigrants.

OBJECTIVE: Jews drink less than other Caucasians and have a higher prevalence of ADH2*2, an allele of an alcohol dehydrogenase gene that protects against heavy drinking. The relationship of ADH2 polymorphisms to lifetime maximum number of drinks per occasion was investigated in recent Russian immigrants to Israel (exposed to heavier drinking in their country of origin), other Israeli Ashkenazis, and Sephardics. METHOD: Seventy-five randomly sampled Israelis participated in a structured interview. ADH2 was genotyped for 68 subjects. RESULTS: ADH2*2 predicted less drinking; however, associations between ADH2 and drinking appeared to differ across the groups, consistent with differences in environmental exposure to heavy drinking. CONCLUSIONS: The findings support a protective effect for ADH2*2 against heavy drinking in Jewish samples but also suggest the importance of environment. Future work should investigate interactions between genes and the environment in larger samples.

Adult↗

Recent drinking history: association with family history of alcoholism and the acute response to alcohol during a 60 mg% clamp.

OBJECTIVE: Family history of alcoholism (FHA) is associated with increased drinking history, which can be a confounding factor in studies of the influence of FHA on the acute response to alcohol. The objective of this analysis was to investigate the association between recent drinking history (RDH) and FHA in a sample of family history positive (FHP; n = 55, 28 women) and family history negative (FHN; n = 55, 29 women) subjects, and to explore the influence of RDH on the response to alcohol during a 60 mg% clamp. METHOD: RDH was measured using daily diary and timeline followback methods. The total number of drinks in the 4-week (TD28) and 1-week (TD07) intervals prior to the study were determined, as well as the number of drinking days in the same intervals. Dependent measures of brain function were obtained at baseline (B0), immediately after the target BrAC was achieved (B1) and 105 minutes later (B2). The alcohol response was quantified as an initial response (ira = B1-B0) and an adaptive response (ada = B2-B1). The association between RDH and the ira and ada measures was tested using multivariate regression. RESULTS: The RDH measures showed a large variance across subjects, with no significant differences between FHP and FHN groups in the study sample. The initial responses for subjective perceptions of "high" and "intoxicated," Alcohol Sensation Scale scores and scores for the grooved pegboardtask were significantly negatively associated with TD28. Acute tolerance to perceptions of "high" and "intoxication" was significantly negatively associated with TD28. CONCLUSIONS: Heavy drinking history is associated with a decreased initial response to alcohol and greater acute tolerance to alcohol, particularly for subjective measures. Although RDH was not associated with FHA in this study, it may be an important determinant of the response to alcohol.

Adult↗

Involvement of acetaldehyde in alcohol addiction.

This article presents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizers and chairs were William J. McBride and Ting-Kai Li. The presentations were (1) Metabolism of ethanol in the brain and the behavioral consequences, by Richard A. Deitrich and Sergey Zimatkin; (2) Catalase production of acetaldehyde as a possible mediator of the psychopharmacological effects of ethanol, by Brian R. Smith; (3) The reinforcing actions of acetaldehyde in the ventral tegmental area, by Zachary A. Rodd-Henricks; and (4) Salsolinol and alcohol addiction, by William J. McBride.

Acetaldehyde↗

Microdialysis of dopamine in the nucleus accumbens of alcohol-preferring (P) rats during anticipation and operant self-administration of ethanol.

BACKGROUND: The present study was designed to test directly whether a contextual stimulus for access to ethanol would acquire the ability to enhance locomotor activity and dopamine efflux in the nucleus accumbens (NAc) of alcohol-preferring (P) rats. The study also explored the association between elevated locomotor activity and NAc dopamine efflux during operant self-administration of ethanol. METHODS: Adult female P rats were randomly assigned to operantly self-administer either 15% (v/v) ethanol or 0.0125% (w/v) saccharin. Both groups were trained in a daily 30-min two-lever concurrent operant task (FR-3) to orally self-administer ethanol or saccharin, with water on the alternate lever. A third (control) group was trained to self-administer water on both levers. All groups were also acclimated in the operant chambers to periods of habituation, anticipation, and postadministration. RESULTS: Compared with controls, the ethanol group, but not the saccharin group, showed significant increases in locomotor activity as well as increased NAc dopamine efflux during the first 10 min of the anticipation period. During the first 10 min of the self-administration period, locomotor activity was significantly increased in both the ethanol and saccharin groups compared with control values. The ethanol group, but not the saccharin group, showed significant increases in NAc dopamine efflux during the 20th and 30th min of the self-administration period and during the first 10 min of the postadministration period. CONCLUSIONS: The findings suggest that acquisition of signal-induced anticipation of self-administered ethanol is associated with increases in locomotor activity and extracellular levels of dopamine in the NAc of P rats. Such associations may be important to the development and maintenance of ethanol-seeking behaviors. The findings also indicate that operant self-administration of ethanol is associated with increases in extracellular levels of dopamine in the NAc of P rats.

Alcohol Drinking↗

Linkage for platelet monoamine oxidase (MAO) activity: results from a replication sample.

BACKGROUND: Monoamine oxidase B (MAO-B) degrades catecholamines in presynaptic nerve endings and is also active in platelets. There is evidence to suggest that platelet MAO-B activity level is controlled by a major genetic locus distinct from the structural gene on the X chromosome. To expand on a prior report, new linkage analyses for platelet MAO-B activity have been performed on the previously analyzed sample (designated the initial sample), on a new sample of families (the replication sample), and on the combined sample. These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA). METHODS: The initial sample consists of 105 extended families providing 1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO activity and genotyped. The replication sample of 157 extended families contains 608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses were conducted using Haseman-Elston based regression on sib pairs and variance component analysis on extended pedigrees, and the importance of cigarette smoking and gender as covariates of platelet MAO-B activity was taken into account. RESULTS: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for linkage across the two distinct datasets by at least one analysis method. Under Haseman-Elston regression of independent sib pairs, only the chromosome 2 region gave lod scores above 1 in both the initial and replication samples. Using all possible pairs, unweighted, for the regression, chromosome 12 gave lod scores above 1 in both samples. For variance component analysis, only the chromosome 9 region gave lod scores above 1 in both samples. CONCLUSIONS: The consistency across datasets of these findings is encouraging. In particular, variance component analysis of extended pedigrees supports a potential linkage of MAO-B activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined sample. Sib-pair regression supports this finding with modest lod scores in the region. Suggestive linkage to chromosomes 2 and 12 from sib-pair analysis is only weakly supported by variance component analysis.

Blood Platelets↗