1-4
5-8
9-12
13-16
17-20
21-24
25-28
29-32
33-36
37-40
41-44
months later, the relapse rates were assessed following the European guidelines of the
Plinius Maior Society (time to first relapse, time to first loss of control, cumulative
abstinence duration).
Lesch types I, III and IV showed that nicotine is used mainly in an addictive way
(ICD-10 positive). Also the Fagerström test showed in these subgroups high levels
(more than 5 points). Type II patients had significantly lower levels in the Fagerström
scale and usually do not smoke in an addictive way. As we could show in the other
study, mentioned above, there are 4 different kinds of craving, also in nicotine
addiction: relaxation, stress, depression, coping.
These differences might lead to different alcohol relapse rates in smoking alcohol
dependent patients. The results of the 6-months follow up and the hypotheses will be
presented, in which periods of alcoholism course tobacco dependence should be
treated. Besides the "When to treat" question we will comment on the second question
of "With what should we treat", discussing different medications, as e.g. nicotine
replacement, bupropione.
BLOOD FROM DIFFERENT MAMMALIAN SPECIES
University, Sweden
: Phosphatidylethanol (PEth) is an abnormal phospholipid formed in
mammalian cells that have been exposed to ethanol. This study was made to
investigate the level of PEth in blood from rats after in vivoalcohol exposure as
compared to the PEth formed in organs. Blood from humans, rats, pig and ferret was
also incubated in vitrowith ethanol for investigation of the PEth formation and
degradation in response to different inhibitors and activators of the enzymes involved.
Methods: Rats were given 9% ethanol in liquid diet for 30 days. Control rats were pair
fed with liquid diet. Lipids from whole blood from the rats were extracted directly
after decapitation. Organs were dissected and frozen. Blood aliquots were incubated
with ethanol and inhibitors or activators at 37 ºC for different times. Whole blood
from humans, pig, and ferret was incubated in the same way as the rat blood. PEth
was analyzed by high performance liquid chromatography (HPLC).
Results:No PEth was found in the rat blood, but PEth was found in the organs. The
levels in organs were comparable to previous results, (obtained after feeding rats
standard lab chow and free per osaccess to liquid bottles containing a 20 % aqueous
ethanol solution as sole source of liquid for 4-6 weeks) although higher amounts were
noted in some organs, maybe depending on the liquid diet. In human blood incubated
with ethanol basal PEth formation was detected. Furthermore in the human blood the
PEth formation could be stimulated and the degradation could be inhibited. In blood
the PEth formation could not be stimulated. The blood from rats exposed to ethanol
for thirty days did not form any PEth in vitro.
Conclusions:PEth is formed in vitro in human blood but not in rat, pig or ferret
blood. Rats form PEth in their organs but not in their blood in vivo.
PHARMACOKINETICS AND REINFORCING
EFFECTS OF ALCOHOL
263 Farmington Avenue, Farmington, CT 06030-2103, USA.
mesolimbic dopamine activation, which seems to be important in the reinforcing
properties of alcohol. Consistent with this model, acute administration to rats of the
tertiary nicotinic receptor antagonist mecamylamine blocks both alcohol consumption
and alcohol-induced dopamine release in the nucleus accumbens. This study was
conducted to test the hypothesis that, during the ascending limb of the blood alcohol
concentration curve, mecamylamine would reduce the stimulating and pleasurable
effects of an intoxicating dose of alcohol in humans.
METHODS: Ten female and 10 male volunteers with no history of alcohol or
substance use disorders, including nicotine dependence, completed the study. During
two laboratory sessions, subjects consumed three aliquots of an alcohol-containing
drink, with a total ethanol content of 0.7 g/kg (in women) or 0.8 g/kg (in men), over a
30-min period. Two hours before the first drink, subjects were pretreated with
mecamylamine or placebo, with the order of sessions counterbalanced. Primary
outcome measures included the Drug Effect Questionnaire, the central stimulation
subscale of the Alcohol Sensation Scale, and the stimulant subscale of the Biphasic
Alcohol Effects Scale. Breath alcohol level (BAL) was examined to identify the
ascending and descending limbs of the blood alcohol curve and to assess
pharmacokinetic interactions between alcohol and mecamylamine.
RESULTS: Significant effects of time, study drug, and their interaction were
observed. Compared with placebo, mecamylamine reduced BAL. After controlling for
BAL at each time point, mecamylamine also reduced the Drug Effect Questionnaire
and Alcohol Sensation Scale stimulant subscale scores, with a trend for a similar
effect on the Biphasic Alcohol Effects Scale score.
CONCLUSIONS: Mecamylamine seems to modify both the pharmacokinetic profile
of alcohol and the rewarding effects of alcohol in healthy volunteers.
HERB, DELAYS ACQUISITION OF ALCOHOL
DRINKING BEHAVIOR IN ALCOHOL-
PREFERRING SP RATS
Paolo Morazzoni3, Ezio Bombardelli3, Mauro A.M. Carai1, Giancarlo
Colombo2, Gian Luigi Gessa1,2,4
Cagliari, Italy; 3Indena SpA, Milan, Italy; 4”Bernard B. Brodie” Department of Neuroscience,
University of Cagliari, Cagliari, Italy.
Salvia miltiorrhiza,
a valued folk medicine in China, are effective in reducing voluntary alcohol intake in
selectively bred Sardinian alcohol-preferring (sP) rats. These studies were conducted
in alcohol-experienced sP rats, i.e. rats which had the opportunity to consume alcohol
for several weeks before the test with Salvia miltiorrhizaextracts, reproducing the
human “active drinking” phase. In contrast, the present study investigated the effect of
IDN 5082, a standardized extract of Salvia miltiorrhiza, on the acquisition of alcohol
drinking behavior in sP rats that were alcohol-naive at the start of the study.
Accordingly, the first administration of IDN 5082 (0, 25, 50 and 100 mg/kg; i.g.)
occurred immediately before alcohol presentation. Alcohol was offered under the
two-bottle free-choice regimen with unlimited access for 24 hours/day. Treatment
with IDN 5082 was repeated once daily for 10 consecutive days. Alcohol, water and
food intakes were recorded once a day.
As shown in Fig. 1, IDN 5082 significantly and dose-dependently delayed acquisition
of alcohol drinking behavior. IDN 5082-induced reduction in alcohol intake was
compensated by an increase in water intake, so that daily total fluid intake remained
virtually unchanged. Daily food intake was significantly higher in the rat groups
treated with IDN 5082 than in the vehicle-dosed group, likely because in the control
group part of the total caloric intake was provided by alcohol.
These results, demonstrating the ability of IDN 5082 to markedly delay the
acquisition of alcohol drinking behavior in alcohol-preferring sP rats, add further
support to the preclinical anti-alcohol profile of Salvia miltiorrhizaextracts.
Salvia miltiorrhizaextract, IDN 5082, on the
acquisition of alcohol drinking behavior in sP rats.
The dashed line indicates the completion of the 10-day treatment period and the start
of the post-treatment period. Each point is the mean ± S.E.M. of n=8.
EFFECT OF ETHANOL ON NMDA GLUTAMATE
RECEPTORS IN CEREBELLAR GRANULE CELLS
SE-17176 Stockholm, Sweden, E-mail: gvido.cebers@ks.se
and in vivoexperiments strongly suggest that NMDA
receptors represent a major target for ethanol in the CNS and that acute application of
ethanol partially inhibits NMDA/glutamate receptor activity. However, the exact
site(s) and the molecular mechanism(s) by which ethanol inhibits the activity of
NMDA receptors in the brain are not known although the involvement of several
NMDA receptor modulatory sites activated by glycine, Mg2+, Zn2+, polyamines and
red-ox agents has been suggested.
In this study we investigated the effects of spermidine, a polyamine site agonist, on
NMDA-induced neurotoxicity and its ability to modulate the inhibitory action of
ethanol on neurotoxicity produced by neurotoxic concentration of NMDA in rat
cerebellar granule cells. We used MTT assay that measures the enzymatic activity in
mitochondria and/or endosome/lysosome compartment that closely correlates with the
cell viability.
Spermidine dramatically potentiated NMDA-induced responses both at non-toxic and
maximally neurotoxic NMDA concentrations. As expected, ethanol concentration-
dependently inhibited the maximal neurotoxicity produced by NMDA. The
potentiating effect of spermidine observed at non-toxic concentrations of NMDA was
not altered by ethanol, as the EC50value for spermidine was not significantly changed