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K Kiianmaa

Publications and source records attributed to K Kiianmaa.

At least 19 recordsLinked to original sources
PubMed2001

Effects of repeated cocaine treatment on striatal dopamine release in alcohol-preferring AA and alcohol-avoiding ANA rats.

Modulation of striatal dopamine (DA) release by acute or repeated cocaine treatment was studied in the nucleus accumbens and caudate-putamen of alcohol-preferring (AA, Alko Alcohol) and alcohol-avoiding (ANA, Alko Non-Alcohol) rats. Cocaine (5-10 mg/kg i.p.) was administered daily for 4 days and the concentrations of extracellular DA measured by in vivo microdialysis on days 1 and 4 in the freely moving rats. The first administration of cocaine increased DA concentration similarly in rats of both lines in both the nucleus accumbens and caudate-putamen. On the 4th day, the effect of cocaine was significantly larger in the nucleus accumbens of AA than in that of ANA rats, whereas no such enhanced effect of cocaine was found in the caudate-putamen of either line. The results suggest that mesolimbic DA release in response to cocaine is sensitized more readily in AA than in ANA rats, which would not only render the former more susceptible to alcohol, but to other drugs of abuse, and might explain our previous findings that AA rats are more susceptible to psychomotor sensitization than ANA rats.

Alcohol Drinking↗
PubMed2001

Dose-dependent decrease in glial fibrillary acidic protein-immunoreactivity in rat cerebellum after lifelong ethanol consumption.

The effects of aging and lifelong ethanol consumption on astrocytic morphology and glial fibrillary acidic protein-immunoreactivity (GFAP-IR) in the cerebellar vermis obtained from ethanol-preferring Alko, Alcohol (AA) rats were analyzed by using computer-assisted image analysis. The ethanol-consuming animals (both male and female) were given ethanol (10%-12%, vol./vol.) as the only available fluid for 21 months (3-24 months), whereas the young (3 months) and the old (24 months) controls received water. In the male rats, but not in the female rats, an age-related decrease in GFAP-IR was found in folia II, VII, and X of the molecular layer, and in turn, an age-related increase was found in folium X of the granular layer, indicating opposite changes in GFAP-IR for male rats due to aging in adjacent brain regions. In the female rats, 21 months of daily average ethanol consumption of 6.6 g/kg resulted in decreased GFAP-IR in folium VII of the molecular layer, and the decrease in cerebellar GFAP-IR correlated with the average daily ethanol intake (r=-.886, P=.019) when folia II, IV, VII, and X were analyzed together. No effect of ethanol on GFAP-IR was detected in the granular layer or in the central white matter of the female rats. There was no change in GFAP-IR in any of the three cerebellar layers of the male rats with average daily ethanol consumption of 3.2 g/kg. These results indicate that the Bergmann glial fibers are the GFAP-expressing structures of the cerebellum most sensitive to moderate-to-heavy chronic ethanol exposure and that this effect is dose dependent.

Age Factors↗
PubMed2001

Effects of lifelong ethanol consumption on drinking behavior and motor impairment of alcohol-preferring AA and alcohol-avoiding ANA rats.

The effects of drinking ethanol throughout a lifetime on voluntary drinking behavior and ethanol-induced motor impairment were studied in alcohol-preferring AA (Alko, Alcohol) and alcohol-avoiding ANA (Alko, Non-Alcohol) rats of both sexes. At the age 3 months, the rats were tested for individual voluntary ethanol (10% vol./vol.) intake and ethanol-induced motor impairment (2 g/kg, i.p.). The rats were housed in group cages, half of them having 12% (vol./vol.) ethanol as the only source of fluid and the other half having free access to water. Food was always available for all animals. At the age of 23 months, their individual voluntary ethanol intake and ethanol-induced motor impairment were tested again. During forced drinking, the females of both strains consumed more ethanol than did the males. The ethanol consumption of the AA and ANA females and the ANA males increased significantly (P < .001) with age, but a slight decrease was seen in the ethanol consumption of the AA males. Time x strain interaction showed a significant (P < .05) difference in the ethanol consumption of male rats, with the AA males having a slight decrease in ethanol consumption with age, whereas the ANA males increased their ethanol consumption. After 19 months of forced ethanol exposure, AA males significantly decreased their individual voluntary ethanol consumption, and individual voluntary ethanol consumption by ethanol-exposed AA males was more pronounced (P < .001) than that of the AA rats that had free access to water (P < .05). For the female AA rats, those having free access to water significantly decreased their voluntary ethanol consumption (P < .05), but those having ethanol only did not. No significant changes in voluntary ethanol consumption with age or with different exposures were seen in the ANA rats. Body weights were higher in the groups having access to water than in the ethanol-only groups, but the differences were not significant within the AA and ANA strains. The ANA rats were significantly heavier in all groups. These results indicate that the voluntarily nondrinking ANA rats can drink almost as much ethanol as the voluntarily drinking AA rats when they are forced to drink ethanol and that lifelong forced ethanol drinking does not change their inherent drinking habits. When sensitivity to ethanol was measured with the tilting-plane test, the old AA female rats were more sensitive to ethanol than were the young ones. The young ANA females were more sensitive than the AA females when tested at 4 months. In males, aging did not produce any differences in ethanol sensitivity.

Aging↗
PubMed2001

Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial.

Several studies have shown the opioid antagonist naltrexone to be effective when combined with psychosocial therapies for the treatment of patients who are dependent on alcohol with fixed medication and time (12 weeks). In this study, 121 nonabstinent outpatients with alcohol dependence (DSM-IV) were treated with sessions of cognitive coping skills (N = 67) or supportive therapy (N = 54) and either naltrexone 50 mg/day (N = 63) or placebo (N = 58) daily for the first 12 weeks and thereafter for 20 weeks only when craving alcohol (i.e., targeted medication) in a prospective one-center, dual, double-blind, randomized clinical trial. The dropout rate for all subjects was 16.5% during the first 12-week period and approximately twice that level by the end of the study. There were no significant group differences in study completion and therapy participation rates. After the continuous medication (12 weeks), the coping/naltrexone group had the best outcome, and coping/placebo had the worst. This difference remained during the targeted medication period (the following 20 weeks). Naltrexone was not better than placebo in the supportive groups, but it had a significant effect in the coping groups: 27% of the coping/naltrexone patients had no relapses to heavy drinking throughout the 32 weeks, compared with only 3% of the coping/placebo patients. The authors' data confirm the original finding of the efficacy of naltrexone in conjunction with coping skills therapy. In addition, their data show that detoxification is not required and that targeted medication taken only when craving occurs is effective in maintaining the reduction in heavy drinking.

Adaptation, Psychological↗
PubMed2001

Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats.

BACKGROUND: Both mu- and delta-opioid receptors have been implicated in the reinforcing actions of ethanol. However, selective opioid receptor antagonists have not altered ethanol intake in all rodent strains consistently, which suggests that genotype may modulate their suppressive effects. Therefore, we tested the effects of the selective mu-antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and the selective delta-antagonist naltrindole in both high-drinking AA (Alko, Alcohol) and heterogeneous Wistar rats. METHODS: AA and Wistar rats were trained to respond for ethanol (10% w/v) in a two-lever operant condition by using a saccharin fading procedure. After stable baseline responding was established, rats were implanted stereotaxically either with a guide cannula above the lateral ventricle or with bilateral cannulas above the nucleus accumbens, basolateral amygdala, or ventral tegmental area. After postoperative recovery, AA and Wistar animals were tested after intracerebroventricular microinjections of either CTOP (0-3 microg) or naltrindole (0-30 microg) or subcutaneous injections of naloxone (0-1 g/kg), which was used as a reference antagonist. Effects of intracerebral microinjections of CTOP and naltrindole (both 0-500 ng) were tested only in Wistar rats. RESULTS: Subcutaneous naloxone and intracerebroventricular CTOP and naltrindole suppressed ethanol self-administration in a similar manner in AA and Wistar rats. Cumulative response patterns indicated that naloxone and naltrindole had no effect on the initiation of responding but suppressed it later during the session, whereas CTOP also affected initiation. In Wistar rats, naltrindole microinjections into both the nucleus accumbens and basolateral amygdala decreased ethanol responding, whereas CTOP was effective only in the amygdala. Injections of these antagonists into the ventral tegmental area had little effect on ethanol intake. CONCLUSIONS: The results confirm previous results which showed that both mu- and delta-opioid receptors are involved in the regulation of ethanol self-administration and indicate that genetic differences between AA and Wistar rats produced by selection do not modify the effects of opioid antagonists. The nucleus accumbens and the basolateral amygdala may be important central sites for the mediation of their suppressive effects.

Alcohol Drinking↗
PubMed2001

Neurobiological processes in alcohol addiction.

This article represents the proceedings of a symposium at the ISBRA Meeting in Yokohama, Japan. The chairs were A. D. Lê and K. Kiianmaa. The presentations were (1) Alcohol reward and aversion, by C. L. Cunningham; (2) The role of sensitization of neuronal mechanisms in ethanol self-administration, by J. A. Engel, M. Ericson, and B. Söderpalm; (3) Alcohol self-administration in dependent animals: Neurobiological mechanisms, by G. F. Koob, A. J. Roberts, and F. Weiss; (4) Stress and relapse to alcohol, by A. D. Lê; (5) Alcohol-preferring AA and alcohol-avoiding ANA rats differ in locomotor activation induced by repeated morphine injections, by P. Hyytiä, S. Janhunen, J. Mikkola, P. Bäckström, and K. Kiianmaa; and (6) Initial sensitivity and acute functional tolerance to the hypnotic effects of ethanol in mice genetically selected for mild and severe ethanol withdrawal convulsions, by I. Ponomarev and J. C. Crabbe.

Alcoholism↗
PubMed2001

Naltrexone suppresses ethanol intake in 6-hydroxydopamine-treated rats.

BACKGROUND: The suppressive effect of opioid antagonists, such as naltrexone, on ethanol intake has been suggested to be based on the interference with ethanol-induced stimulation of dopamine release in the nucleus accumbens. The aim of this study was to determine whether reduction of dopamine innervation to the nucleus accumbens with the neurotoxin 6-hydroxydopamine (6-OHDA) alters naltrexone-induced suppression of ethanol consumption. Because the mesolimbic dopaminergic neurons have also been implicated in ethanol reinforcement, the effects of 6-OHDA on the maintenance and acquisition of ethanol intake were also studied. METHODS: To damage accumbal terminals of the mesolimbic dopamine neurons, alcohol-preferring Alko Alcohol (AA) rats were given bilateral injections of 6-OHDA or vehicle into the nucleus accumbens after pretreatment with desipramine and pargyline. The effect of the lesion on the acquisition or maintenance of ethanol self-administration was studied in animals having continual access to ethanol solution (10% v/v) and water. Subsequently the effect of naltrexone on ethanol consumption was determined. RESULTS: Naltrexone (0.03-3.0 mg/kg subcutaneously) suppressed ethanol consumption in a dose-dependent manner both in 6-OHDA-treated and control animals given a daily 90-min access to ethanol solution. When the rats had continual access to ethanol, there was a clear day-to-day decline in ethanol intake during the first 5 days of the 7-day naltrexone treatment (10 mg/kg subcutaneously). 6-OHDA treatment had no effect on either the acquisition or maintenance of ethanol self-administration. Postmortem analysis of the brain dopamine content revealed approximately 92% depletion of dopamine in the nucleus accumbens of the 6-OHDA-treated rats. CONCLUSIONS: The suppressive effect of naltrexone does not depend on naltrexone's interaction with dopaminergic terminals in the nucleus accumbens. Furthermore, the role of the mesolimbic dopamine pathway is probably not central either in the acquisition or maintenance of ethanol self-administration in alcohol-preferring AA rats.

Animals↗
PubMed2000

The effects of nicotine on locomotor activity and dopamine overflow in the alcohol-preferring AA and alcohol-avoiding ANA rats.

The aim of the study was to investigate the importance of the interaction between central dopaminergic and cholinergic mechanisms for ethanol reinforcement. This was done by comparing the effects of nicotine on locomotor activity and release of dopamine in the nucleus accumbens of the alcohol-preferring Alko Alcohol (AA) and alcohol-avoiding alko non-alcohol (ANA) rats. Nicotine was administered acutely (0.25, 0.50 or 0.75 mg/kg, s.c.) or repeatedly once daily (0.5 mg/kg, s.c.) for 8 days. An acute dose of nicotine increased locomotor activity and the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) measured with in vivo microdialysis suggesting stimulation of dopamine release by nicotine. No difference in the stimulation of locomotor activity or in the increase in the extracellular concentrations of dopamine or its metabolites by nicotine was found between the rat lines. The concentrations of nicotine in the plasma were also identical. The rats treated repeatedly with nicotine showed a progressive increase in locomotion. On the challenge day, 1 week after termination of nicotine or saline injections, rats previously treated with nicotine were activated more by nicotine than saline-treated rats. This behavioral sensitization was not accompanied by an increase in the amplitude of the neurochemical response to nicotine, but the duration of the increase in the levels of DOPAC was longer in the nicotine than saline-treated animals. The increases in locomotor activity and metabolite levels were, however, similar in both rat lines. These data suggest that differences in the interaction of central dopaminergic and cholinergic mechanisms probably do not contribute to the difference in ethanol self-administration between the AA and ANA rat lines.

Alcohol Drinking↗
PubMed2000

Opioid propeptide mRNA content and receptor density in the brains of AA and ANA rats.

Recent evidence has indicated an association between the rewarding effects of ethanol intake and endogenous opioid activity. The present studies examine the presence of differences in opioid peptide mRNA content and mu and kappa opioid receptor densities, between ethanol naive AA and ANA rats bred selectively for their high and low alcohol consumption, respectively. In situ hybridization was used to compare the content of proopiomelanocortin, proenkephalin and prodynorphin mRNA in distinct brain regions known to be involved in the reinforcing properties of addictive drugs, between rats from each line. Results indicated that AA rats had a significantly greater content of proopiomelanocortin mRNA in the arcuate nucleus of the hypothalamus, of proenkephalin mRNA in the prefrontal cortex and of prodynorphin mRNA in the mediodorsal nucleus of the thalamus (p < or = .05). Receptor autoradiography was performed using 3H-labeled ligands specific for mu and kappa opioid receptors. AA rats were found to have a greater density of mu opioid receptors in the shell region of the nucleus accumbens and prefrontal cortex, but a lower density of kappa opioid receptors in the ventromedial hypothalamus, compared to ANA rats. The present data demonstrate the presence of inherited differences in the activity of distinct components of the endogenous opioid system in some brain regions associated with the processes of reward and reinforcement; and as such, may play a role in determining differences in ethanol drinking between AA and ANA rats.

Alcoholism↗
PubMed2000

Effects of repeated morphine on cerebral dopamine release and metabolism in AA and ANA rats.

Cerebral dopaminergic mechanisms were studied in the nucleus accumbens and caudate-putamen of alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Non-Alcohol) rats after 4-day repeated morphine treatment. This treatment has been shown to enhance the locomotor activity stimulating effect of morphine in the AA but not in the ANA rats. Morphine (1 or 3 mg/kg) or saline was administered subcutaneously once daily and the extracellular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured, in freely moving rats by in vivo microdialysis on days 1 and 4. Morphine increased accumbal DA, DOPAC and HVA similarly in rats of both lines, and no sensitization of DA release or metabolism was seen in rats of either line given morphine repeatedly. In the caudate-putamen, morphine increased DA, DOPAC and HVA significantly only in the AA rats. During repeated treatment, the morphine-induced elevation of DA metabolites, but not that of DA, was enhanced similarly in rats of both lines. These results suggest that the effects of acute morphine administration on nigrostriatal dopaminergic mechanisms are stronger in the AA than in the ANA rats, whereas the effects of morphine on mesolimbic dopaminergic systems do not differ. Furthermore, in rats of both lines, repeated morphine treatment enhanced the responses of the nigrostriatal dopaminergic systems similarly, but no enhancement occurred in the mesolimbic systems of rats of either line. These findings do not support the critical role of accumbal dopaminergic systems in morphine-induced behavioural sensitization.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Effects of chronic alcohol consumption on the expression of different NR1 splice variants in the brain of AA and ANA lines of rats.

Following chronic alcohol treatment alterations in N-methyl-D-aspartate receptor subunit 1 and 2 (NR1 and NR2), mRNA and protein levels have been reported. The NR1 gene undergoes alternative RNA splicing, resulting in eight splice variants, which were shown to differ in their sensitivity to alcohol. Here, we studied mRNA and protein levels of NR1 splice variants in alcohol-preferring (AA) and alcohol-nonpreferring (ANA) rat lines under basal conditions (alcohol-naive), and following chronic alcohol consumption. mRNA levels of three NR1 splice variants (NR1-1, NR1-2, NR1-4), and the protein levels of NR1 (NR1-1/NR1-2), and of NR1 alternative C-terminus (NR1-3/NR1-4) were determined in the hippocampus and nucleus accumbens by competitive RT-PCR and Western blot analysis, respectively. No significant differences in NR1 mRNA, or protein levels were found in the nucleus accumbens between the two rat lines under basal conditions, or following chronic alcohol consumption. In the hippocampus of alcohol-naive rats, the NR1-4 mRNA content was significantly higher in ANA compared to AA rats, however, no significant difference could be detected at the protein level. Following chronic alcohol consumption, the protein level of the NR1 alternative C-terminus (NR1-3/NR1-4) was significantly higher in AA rats compared to the corresponding control. Taken together, these results suggest: (i) brain site-specific alterations in NMDA receptor subunit composition occur following chronic alcohol consumption. (ii) In the hippocampus, NR1 splice variant mRNA levels differ between AA and ANA rats. (iii) The mRNA levels and protein levels of NR1 splice variants are differentially affected by chronic alcohol consumption.

Alcohol Drinking↗
PubMed1999

Effects of lifelong ethanol consumption on rat sympathetic neurons.

In this experiment we studied the effects of aging and lifelong ethanol consumption on rat peripheral sympathetic neurons. The aim was to find out the possible differences in the vulnerability to ethanol-induced neuronal degeneration between rats of both genders, or between the alcohol-avoiding (ANA) and the alcohol-preferring (AA) lines of rat. The superior cervical ganglia (SCG) of 40 male and 41 female AA and ANA rats were analyzed. The ethanol-exposed groups had 12% ethanol as the only available fluid from 3 to 24 months of age. The young (3 months) and old (24 months) control groups had water instead. SCG neuronal density, volume, and total neuron number were measured by unbiased morphometric methods. No gender difference was seen in either the volume of the SCG or in the SCG neuron number. The volume of the ganglion was significantly increased with age, but the total neuron number did not change. Neuronal density was significantly decreased with age, but lifelong ethanol consumption induced no further decrease. SCG neuron number in the ethanol-exposed groups did not differ from the age-matched or young control groups, but a significant negative correlation (r = -0.70, p<0.01) was seen between individual ethanol consumption and the number of SCG neurons in the female rats. The amount of lipopigment in the SCG was increased in the ethanol-exposed male rats. These results suggest that the peripheral sympathetic neurons are rather resistant to ethanol-induced degeneration, and that no major gender or line differences exist in this respect.

Aging↗
PubMed1999

Brain ethanol levels after voluntary ethanol drinking in AA and Wistar rats.

Brain ethanol was monitored in the nucleus accumbens with one minute microdialysis and headspace gas chromatography in male Wistar and alcohol preferring AA (Alko Alcohol) rats after voluntary limited access consumption without food restriction. The rats drank 0.93 +/- 0.14 (Wistar) and 0.73 +/- 0.07 g/kg (AA), with a resulting mean maximal brain ethanol level of 15.9 mM and 14.1 mM, respectively. Maximum brain ethanol levels for individual AA rats were in the range 9.4-33.6 mM, median 15.5 mM and for the individual Wistar rats in the range 2.5-35.2 mM, median 17.8 mM. There was a significant but not perfect correlation between the amount ethanol drunk and the resulting ethanol level in the nucleus accumbens, probably because of the rats not being food deprived before the experiment. The results show that rats drink pharmacologically meaningful doses in a voluntary limited access situation and that blood samples can give us a hint about the level attained in the brain, but to know the early brain concentration after drinking, microdialysis is an excellent tool.

Alcohol Drinking↗
PubMed1999

Drinking habits and prevalence of heavy drinking among primary health care outpatients and general population.

AIMS: To identify the target group for brief alcohol intervention in primary health care and to compare the prevalence of heavy drinking in two different primary health care populations and the general population in the same geographical area. DESIGN: Drinking data were collected from outpatients of primary health care by a questionnaire containing the CAGE test and quantity-frequency alcohol consumption questions and from a sample of the general population by a telephone survey, including the CAGE. The index of heavy drinking was for men three, and for women two, affirmative answers in CAGE which though not specifically a consumption questionnaire is a good marker of heavy drinking. SETTING: Two different primary health care populations (primary health care clinic and occupational health care clinic) and the general population in a Finnish health care area. PARTICIPANTS: Consecutive 1861 primary health care clinic and 2942 occupational health care clinic outpatients and 544 randomly selected adults in the general population, contacted by telephone. FINDINGS: The primary health care clinic patients drank significantly more per occasion than the patients of the occupational health care clinic (75 vs. 66 g. in men; 33 vs. 27 g. in women) and fewer times per week (0.8 vs. 0.9 in men; 0.5 vs. 0.6 in women). The patients in the primary health care clinic also reported drinking more per week (76 vs. 67 g. in men; 23 vs. 19 g. in women); among women the difference was significant. Among men the prevalences of heavy drinking in the primary health care clinic, occupational health care clinic and general population were 20%, 17% and 16%, respectively (p > or = 0.05). Among women the corresponding figures were 9%, 6% and 13% (p < 0.05). CONCLUSIONS: The high prevalence of heavy drinking found in the study confirms the importance of brief intervention by general practitioners. The study also indicates that prevalence and drinking habits depend on the type of clinic and heavy drinkers in general may not be over-represented in primary health care. This study raises the question, especially among women, of how to reach and to provide health advice to those heavy drinkers who do not attend primary health care facilities.

Adult↗
PubMed1999

Effects of dexmedetomidine on rat locus coeruleus and ethanol withdrawal symptoms during intermittent ethanol exposure.

In the present study, the neuroprotective effects of dexmedetomidine on rat locus coeruleus were studied during a 5-week intermittent ethanol exposure. Male Wistar rats (3 to 4 months old) were given ethanol or isocaloric sucrose by intragastric intubations three times a day for 4 days, which was followed by a 3-day withdrawal period. This 7-day cycle of ethanol exposure and withdrawal was repeated five times. Dexmedetomidine (at a dose decreasing from 30 microg/kg to 10 microg/kg, s.c.) was given to the treatment group during the withdrawal phase. The results showed that, during the 5-week experiment, dexmedetomidine significantly relieved the ethanol withdrawal syndrome, measured as the sum of the three most specific symptoms (rigidity, tremor, and irritability). The total neuron number of locus coeruleus (LC) decreased in the ethanol-treated group by 24%, compared with the nontreated control group and by 11%, compared with the sucrose-treated control group. Interestingly, the LC neuron numbers were found to decrease in the sucrose-intubated rats as well, compared with the nontreated control group. Dexmedetomidine was found to relieve ethanol-induced neuronal loss in the LC. Dexmedetomidine might be a new interesting alternative in the treatment of ethanol withdrawal syndrome, particularly due to its possible neuroprotective effects in the central nervous system.

Adrenergic alpha-Agonists↗
PubMed1998

Lifelong ethanol consumption and loss of locus coeruleus neurons in AA and ANA rats.

The effects of lifelong ethanol exposure and aging on the morphology of the locus coeruleus (LC) were studied in the AA (Alko, Alcohol) and ANA (Alko, Nonalcohol) rats of both sexes. The ethanol-consuming (EtOH) rats were given 12% (v/v) ethanol as the only drinking fluid from 4 to 22 months of age, whereas the young (3-month-old) and aged (24-month-old) controls had only water available. The total LC neuron numbers were obtained by using the unbiased disector method. In the AA line, as we have previously reported. the EtOH female and male rats displayed a 26-30% loss of LC neurons compared with the controls. In the ANA line, the EtOH females had 30% fewer LC neurons than the controls (EtOH 1579 +/- 377 vs. controls 2264 +/- 269, ANOVA p < 0.01), whereas the EtOH males showed no neuron loss compared to the controls (EtOH 1848 +/- 525 vs. controls 2216 +/- 152, ANOVA NS). However, taking into account (sex by line ANCOVA) the markedly higher ethanol intake of the female rats in both lines, no gender or line differences in the ethanol-induced LC degeneration were detected. Neither was there any difference in LC neuron numbers between the young and old control rats of either line of rats. In conclusion, chronic alcohol consumption, not aging per se, damages the LC neurons in experimental animals.

Acetaldehyde↗
PubMed1998

Dopamine release during ethanol drinking in AA rats.

The dopamine overflow in the nucleus accumbens of rats from the high alcohol drinking AA line was measured by microdialysis before, during, and after one-half hour sessions of cued drinking of ethanol flavored with saccharin and peppermint or, as a control, saccharin-peppermint drinking. The animals had had extensive previous experience with ethanol drinking. Self-administration of the ethanol solution did not raise the dopamine level substantially: there was a small (17%) but significant increase only during the first 10 min after the onset of drinking. Giving the rats a cue for ethanol, which was part of their daily routine drinking regime, did not raise the dopamine level before ethanol was presented to the rats (i.e., during "anticipation"). The results are consistent with our previous studies showing a lack of a large ethanol-induced dopamine response in rats with previous experience of drinking ethanol and with the idea that although dopamine may play some role in alcohol drinking, it is not the central substrate producing the reinforcement from ethanol in AA rats.

Alcohol Drinking↗