Use and misuse of the concept of craving by alcohol, tobacco, and drug researchers.
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Alcohol Drinking↗
Biomedical subjects
D A Wilkinson
Publications and source records attributed to D A Wilkinson.
Dimensions of multiple drug use and a typology of drug users.
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Adolescent↗
Alcohol-induced brain damage: confounding variables.
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Age Factors↗
The chronic effects of alcohol on memory. A contrast between a unitary and dual system approach.
Recent studies have indicated that impairment of memory is a common cognitive deficit related to long-term alcohol consumption. Such deficits range from subtle disturbance through a "subclinical" amnesic disorder to full-blown Korsakoff syndrome. This finding is congenial with the hypothesized continuum of alcohol-related impairment of memory. Among alcoholics, this memory impairment appears to be etiologically distinct from the commonly observed deficits in abstracting and problem-solving abilities. In the present chapter, a dual and a unitary formulation of memory are contrasted in their ability to present a coherent account of what memory tasks Korsakoff amnesics can and cannot do. The explanations offered by unitary theory are weak compared to those derived from the theory that memory consists of two distinct systems--experiential and abstractive memory. We indicate how the pattern of responding on standard clinical tests of memory can be coherently analyzed post hoc within the dual formulation. A number of experimental predictions are also presented based on the theory that Korsakoff amnesics have a profound impairment of experiential memory, whereas the abstractive system is essentially normal. Such experiments should clarify the nature both of Korsakoff amnesia and of memory itself. In conclusion, we indicated that memory disorders related to alcoholism can be understood in terms of a gradient, or continuum, of impairment of the experiential system.
Alcohol Amnestic Disorder↗
A subtransition in a phospholipid with a net charge, dipalmitoylphosphatidylglycerol.
Suspensions of dipalmitoylphosphatidylglycerol (DPPG) have been analyzed by differential scanning calorimetry, equilibrium and differential scanning dilatometry, and X-ray diffraction techniques. After the DPPG suspensions are stored several days at 2 degrees C, a new phase transition is observed at a lower temperature than either the main transition or the pretransition. This subtransition has an enthalpy of about 6 kcal/mol and occurs at about 20 degrees C, the exact temperature depending on the buffer used. The lipid partial specific volume increases by 0.035 mL/g upon warming through the subtransition. X-ray diffraction patterns from suspensions in the subgel phase contain orders of a lamellar repeat and several additional sharp and broad wide-angle reflections between 8 and 2 A. As the water content in the specimen is reduced, the lamellar repeat period decreases, whereas the spacings and intensities of these additional wide-angle reflections are unchanged. These data indicate that on incubation at 2 degrees C the lipid molecules crystallize in the plane of each bilayer. X-ray experiments also show that this subgel phase converts to the normal L beta' gel phase above the subtransition.
Calorimetry, Differential Scanning↗
Computerized tomographic scan assessment of alcoholic brain damage and its potential reversibility.
The assessment of alcoholic brain damage by computerized tomographic (CT) scanning is reviewed and discussed. Alcoholics showed greater cerebral atrophy than aged-matched neurological controls. Supratentorial atrophy measurements correlated significantly with some neurobehavioral assessment measures. The cerebral atrophy reversed in some subjects with maintained abstinence. Computerized assessment of cerebral spinal fluid volume (cerebral atrophy) and mean cerebral density showed decreased cerebral spinal fluid volume and increased cerebral density with maintained abstinence over 4 weeks in a group of 20 alcoholics. CT cerebellar measurements demonstrated atrophy in many subjects, but these measurements did not correlate with measures of ataxia, cognitive impairment, supratentorial atrophy measurements, or age. An example of a magnetic resonance imaging scan of an alcoholic is given. Its advantages in avoiding bony artifact for posterior fossa atrophy estimations and its potential for in vivo description and localization of central nervous system metabolic abnormalities in alcoholism are discussed.
Adult↗
Beta-adrenergic [( 3H]CGP-12177) binding to brain slices and single intact pineal glands.
We have characterized and quantified the binding of [3H]CGP-12177 to beta-adrenergic receptor sites in slices (300 microns) of rat cerebral cortex. The receptors are stereospecific, saturable and of high affinity. Binding of [3H]CGP is readily reversible and demonstrates appropriate drug specificity. This assay method allows the demonstration of isoproterenol-induced down-regulation (internalization) of beta-adrenoreceptors. Receptor recycling is observed at 37 degrees C in the absence of beta-agonist but can be blocked by low temperature (0 degree C) or by monensin. beta-Adrenoreceptors can also be labeled and quantified in intact, single pineal glands of rat, mouse and hamster. Rat pineals contain approximately 10 times more binding sites than do hamster or mouse pineals and up to 8 times more sites than found in rat cerebral cortex. Rat pineal [3H]CGP binding can be up- and down-regulated but not to the same degree as seen in brain slices. This assay method is simple, rapid and provides new opportunities for the study of other receptor types in intact tissue.
Adrenergic beta-Antagonists↗
The noradrenergic neurotoxins DSP4 and xylamine bind to opiate receptors.
DSP4 and xylamine compete with [3H]-naloxone for opiate binding sites with IC50 values of approximately 1 microM. This effect can be blocked by excess naloxone but not by the noradrenaline uptake inhibitors cocaine or desipramine. Other drugs containing the 2-chloroalkylamine structure--phenoxybenzamine, dibenamine, chloroethyl clonidine, the cholinotoxin AF-64 and 2-dimethylaminoethyl chloride--were similarly tested. Phenoxybenzamine and dibenamine were also able to compete with [3H]-naloxone for binding at the opiate receptor. Experiments in vivo demonstrated that DSP4, like other opiates, can rapidly reduce LH secretion in the rat. This effect is prevented by naloxone but not by desipramine. These data suggest the use of caution in interpreting the results of experiments in which DSP4 and xylamine are used as "specific" noradrenergic uptake inhibitors or as neurotoxins.
Amines↗
Gonadal steroid-induced modification of opiate binding sites in anterior hypothalamus of female rats.
It has been previously shown that treatment with estradiol valerate (EV) or 17 beta-estradiol produces enhanced tritiated naloxone binding in the hypothalamus of the rat. In the present study, the following questions were addressed: Does this effect occur in the preoptic and anterior hypothalamic areas (regions associated with the cyclic gonadotropin surge)? Is chronic estradiol (E2) exposure essential in producing a long-term elevation in opiate binding? Is the effect steroid specific? The results indicated that chronic, but not acute, exposure to estradiol induces and maintains enhanced binding in the anterior hypothalamus. E2 exposure was most effective in this regard, testosterone (T) significantly less so, and 5 alpha-dihydrotestosterone (DHT) caused no elevation in binding above castrate control levels. Furthermore, both T and DHT significantly inhibited the estradiol effect. In addition, intact animals showed significantly less binding than their ovariectomized counterparts, suggesting that the ovary normally produces a factor that suppresses opiate binding. Enhancement of anterior hypothalamic opiate binding is therefore dependent on chronic exposure to E2, and the marginal effects of T are probably due to in situ aromatization. E2 enhancement of opiate binding may be causal in producing the hypothalamic aberration that results in the EV-induced polycystic ovarian condition.
Animals↗
Metastability in the phase behavior of dimyristoylphosphatidylethanolamine bilayers.
A new subgel phase is demonstrated to occur in hydrated dimyristoylphosphatidylethanolamine ( DMPE ) by using dilatometric and calorimetric techniques. The formation of the subgel phase takes place very slowly at temperatures near 0 degree C, but it can still be observed at 25 degrees C. Once formed, the subgel phase melts (delta Hh = 16.0 +/- 0.6 kcal/mol and delta V = 0.085 +/- 0.014 mL/g) directly into the liquid-crystalline phase at a temperature, Th = 56.3 degrees C, that is higher than the gel to liquid-crystalline transition temperature, Tm = 49.6 degrees C. Thus, the gel phase appears to be metastable over its entire temperature range. In this regard, DMPE behaves differently from dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine but similarly to dilaurylphosphatidylethanolamine . This unusual long-lived metastability provides cells an additional option in determining the properties of membranes.
Chemical Phenomena↗
Brain slices in radioligand binding assays: quantification of opiate, benzodiazepines and beta-adrenergic ([3H] CGP-12177) receptors.
We have characterized and quantified specific binding of [3H]-flunitrazepam (FNZ; (benzodiazepine), [3H]-naloxone (NAL; (opiate) and [3H] CGP-12177(CGP; (beta-adrenergic) to thick slices (230-400 micron) of mouse and rat brain. The binding sites are stereospecific, saturable and of high affinity. In all cases, the binding of the ligands is readily reversible and demonstrates the appropriate drug specificity. In mouse brain [3H]-NAL binding is elevated by chronic treatment with naloxone (via capsules). We have been unsuccessful in quantifying beta adrenoreceptors with the archetypal ligand [3H]-dihydroalprenolol (DHA). However, the use of [3H]-CGP 12177 enabled us to detect high-affinity beta adrenoreceptors in brain slices. [3H]-CGP also permits the demonstration of rapid and reversible agonist-induced down-regulation (internalization) of beta binding sites. We have been successful in quantifying beta adrenergic sites in single pineal glands of rat and hamster.
Animals↗
Partially reversible cerebral atrophy and functional improvement in recently abstinent alcoholics.
52 recently abstinent chronic alcoholics were given repeated psychological tests and 20 of these had repeated CT scans. The first scan was done within 5 weeks of the last drink. The degree of measurably reversible cerebral atrophy on CT scan correlated negatively with the interval between the last drink and the first CT scan. Significantly more reversibility of cerebral atrophy was noted in those subjects claiming interscan abstinence. There were positive correlations between functional improvement scores on neurological exam and reversible cerebral atrophy measurements. Significant improvement on psychological test performance was restricted to patients tested initially within 3 weeks of the last drink. Both the CT results and the psychological test results suggest that reversible changes occur soon after the cessation of drinking.
Alcoholism↗
Benzodiazepine receptors in fish brain: [3H]-flunitrazepam binding and modulatory effects of GABA in rainbow trout.
We have identified and partially characterised benzodiazepine binding sites in whole brain membranes of male rainbow trout. In terms of Bmax and KD values trout brain receptors are remarkably similar to those in rat and human brain. The Hill coefficient was 0.98, indicating a single binding site. GABA (10(-4) M) was able to significantly elevate binding of [3H]-FNZ through a change in KD rather than Bmax. This effect was prevented by the GABA receptor antagonist bicuculline methiodide.
Animals↗
Prolonged estrogen treatment induces changes in opiate, benzodiazepine and beta-adrenergic binding sites in female rat hypothalamus.
Exposure of the rat brain to estradiol is known to modify certain neurotransmitter binding sites. We have now examined the influence of long-term (3 months) treatment with this steroid. Opiate and benzodiazepine receptors are both elevated in hypothalamus but not in amygdala or cerebral cortex. In contrast, the affinity, but not maximum binding, of hypothalamic beta-adrenergic sites is reduced 5-fold. Our results confirm and extend previous reports that hypothalamic neurotransmitter binding sites are particularly sensitive to estrogen feedback.
Amygdala↗
Photoperiodic modification of opiate but not beta-adrenergic or benzodiazepine binding sites in hamster brain.
Exposure to short photoperiods induces gonadal regression in the golden hamster. This is accompanied by a fall in serum gonadotropins and changes in hypothalamic neurotransmitter turnover. We have attempted to correlate these changes with alterations in neurotransmitter receptor binding parameters. Compared to hamsters held in long photoperiods, opiate ([3H] naloxone) binding in hamsters exposed to short photoperiods is elevated in whole brain and in cerebral cortex but not in hypothalamus. However, beta-adrenergic ([3H] dihydroalprenolol) and benzodiazepine ([3H] flunitrazepam) binding are unaffected in whole brain, cerebral cortex or hypothalamus. Thus, changes in hypothalamic noradrenaline turnover rate previously reported may not be correlated with changes in beta-adrenergic binding.
Alprenolol↗
Cerebellar, cortical and functional impairment in toluene abusers.
24 solvent abusers (mean age 23 +/- 4.4 years +/- SD) were studied in hospital. They reported using substances containing a mean of 425 +/- 366 mg of toluene per day for 6.3 +/- 3.9 years. There was no laboratory evidence of under-nutrition. No withdrawal symptoms were observed. Marked impairment was observed in neurological and neuropsychological test performances in 65% of the sample. Cerebellar symptoms were particularly prominent. The impairment was significantly correlated with CT scan measurements of the cerebellum, ventricles and cortical sulci, all of which abnormal in comparison to age-matched controls. CSF abnormalities were elevated C1-, low PO2 and very low anion gap. The duration of abuse was only weakly correlated with neurological scores. After 2 weeks of abstinence, several liver function tests which were abnormal on admission had recovered, but only minimal changes in the CNS symptoms were observed.
Adolescent↗
Assessment of neurological dysfunction and recovery in alcoholics: CT scanning and other techniques.
The neurological complications of alcoholism are briefly mentioned. The cerebral dysfunction associated with long-term alcohol abuse is discussed in detail. The techniques used for measurement of functional deficits and cerebral morphological abnormalities are outlined. Significant correlations were noted between cerebral atrophy and functional measurements. Age was the most important covariate except in those alcoholics with the Wernicke's syndrome or an amnesic syndrome (with VIQ-MQ greater than or equal to 15). Partial reversibility of functional and cerebral atrophy measurements was noted in some recently abstinent alcoholics. EEG abnormalities also tended to improve in some alcoholics. A prolonged but resolving CSF acidosis was noted in many subjects. Possible biological mechanisms and the treatment implications of the sometimes slow (weeks to months) but remarkable functional recovery seen in some recently abstinent alcoholics are discussed.
Alcoholism↗
Dilatometric studies of the subtransition in dipalmitoylphosphatidylcholine.
The phase transition between the newly discovered low-temperature subgel phase and the gel phase of dipalmitoylphosphatidylcholine has been studied by using dilatometry. Equilibrium measurements show that the subtransition upon heating is centered at 13.5 degrees C, has a dilatometric half-width of 0.6 degree C, and comprises a specific volume change of 0.009 mL/g (about one-fourth the size of the main transition). When the gel phase is cooled, the subtransition does not occur until below 5 degrees C. The rate of formation as a function of incubation temperature for 1 degree C less than TI less than 6 degrees C was determined; it is not well fit by quantitative theories based upon homogeneous nucleation. However, some form of nucleation is present since temperature-jump studies show that once the subgel phase has started to form, it continues to grow in the range 6 degrees C less than TJ less than 12.8 degrees C. Thus, the true transition temperature lies between 12.8 and 13.5 degrees C, but nucleation of the subgel phase is severely retarded above 6 degrees C, leading to the large hysteresis observed upon cooling.
Calorimetry↗