Acetylation Phenotype in Abstinent Alcoholics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65222/1/j.1530-0277.1989.tb00285.x.pd

Neurochemical Correlates of Sympathetic Activation during Severe Alcohol Withdrawal

Cerebrospinal fluid (CSF) was obtained from 17 patients during acute alcohol withdrawal. Eight of these 17 patients had a second lumbar puncture a mean of 11.9 ± 8.1 (sd) days later, when the clinical signs of alcohol withdrawal had subsided. CSF 3‐methoxy‐4‐hydroxyphen‐ylglycol concentrations declined significantly (p < 0.05) during the course of alcohol withdrawal from 52.0 ± 22.1 (sd) to 39.6 ± 12.6 pM/ml. In early withdrawal, there was a significant positive correlation between CSF norepinephrine (NE) and corticotropin releasing hormone (CRH) concentrations (r= 0.95, p <0.001). Both NE and CRH concentrations correlated positively with diastolic blood pressure (r= 0.88, p < 0.001 and r= 0.62, p < 0.05, respectively). In all samples, CSF 5‐hydroxyindole acetic acid concentrations correlated positively with CSF‐homovanillic acid concentrations (r= 0.83, p < 0.001). These findings indicate significant perturbations of the noradrenergic neuronal system and a change in CRH‐NE interactions during acute alcohol withdrawal

Oral self-administration of ethanol, phencyclidine, methadone, pentobarbital and quinine in rhesus monkeys

Rationale: Simultaneous and sequential drug use among clinical populations is the norm, whereas the pattern of self-administration of multiple drugs among non-human primate populations has not been thoroughly explored. Objectives: To determine the relationship between the preferences and intakes of a large group of rhesus monkeys exposed to various orally available solutions. Methods: Thirteen male and eleven female young adult rhesus monkeys ( Macaca mulatta ) were exposed to orally available drug solutions using a concurrent choice (drug and water) procedure, where fluid delivery was made contingent upon single spout contacts (fixed ratio one). Results: Ethanol (0.25–16% w:v) produced biphasic effects on the number of fluid deliveries obtained, with peak ethanol preferences over water demonstrated at the 1–2% w:v concentrations. No preferences for the N -methyl- d -aspartate receptor antagonist phencyclidine or water were demonstrated at lower concentrations (0.0078125–0.125 mg/ml) and, at higher concentrations (0.25, 0.5 mg/ml), a preference for water was demonstrated. The µ opioid receptor agonist methadone (0.001–0.3 mg/ml) and the prototypic bitter substance quinine (0.001–0.3 mg/ml) failed to produce preferences for drug or water. A large preference for water over the barbiturate pentobarbital (0.01–3 mg/ml) was also demonstrated. After rank-ordering the subjects based on their drug preferences or intakes, modest to no correlations across drugs were demonstrated. Conclusions: These results reveal that a robust ethanol preference is not predictive of a preference for drugs of abuse from other classes and suggests that fluid intakes were correlated, irrespective of the presence or absence of drug in the solution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41968/1/213-147-2-113_91470113.pd

Cerebrospinal fluid thyrotropin-releasing hormone concentrations in alcoholics and normal controls

Alterations in hypothalamic-pituitary-thyroid axis function have been reported in alcoholism. Blunting of the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) occurs in approximately 25% of alcoholics patients. Using a sensitive radioimmunoassay that allows TRH itself to be measured in cerebrospinal fluid (CSF), CSF concentrations of TRH were measured in alcoholics and normal controls. There was no significant difference in TRH concentrations between the groups. However, among the controls there was a significant correlation between CSF concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and CSF concentrations of TRH. This correlation was lacking in the alcoholics. These findings are of interest because basic neurobiological studies have reported that TRH and serotonin are co-localized in certain neurons in the rat central nervous system