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K Kiianmaa

Publications and source records attributed to K Kiianmaa.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

Effects of lifelong ethanol consumption on cerebellar layer volumes in AA and ANA rats.

Aging and chronic alcohol consumption can cause degenerative changes in the cerebellar cortex. In this study, the effects of aging and lifelong alcohol consumption on cerebellar cortical layer volumes (molecular and granular) and also white matter layer volumes were studied in alcohol-preferring (AA) and nonpreferring (ANA) rats of both sexes. The ethanol-consuming animals (EtOH) had 12% (w/v) ethanol as the only available fluid from 4 to 22 months of age, whereas the young (3 month) and old controls (24 months) had only water to drink. The volumes of molecular, granular, and white matter layers of the cerebellar vermis in folia II, IV, VII, and X were measured by using systematic sampling and a point-counting method. The volumes of the granular and white matter layers showed consistent increase between 3 and 24 months of age, whereas the volume of the molecular layer remained unchanged with increasing age. Individual ethanol intake was measured over a 1-week period at the beginning and at the end of chronic ethanol exposure. Significant (ANOVA, p = 0.000) sex difference was found in the drinking behavior in both lines, with females consuming more alcohol than males (daily ethanol consumption at 22 months of age 3.2 +/- 0.3 vs. 7.1 +/- 0.3 g/kg for AA males and females; 3.2 +/- 0.3 vs. 5.4 +/- 0.4 g/kg for ANA males and females, respectively). The only ethanol-induced effect on the cerebellum was observed in ANA-EtOH females with a 15% reduction in the volumes of the molecular and granular layer in folium II compared with age-matched controls and a significant (p < 0.05, analysis of covariance with ethanol intake as a covariate) line difference in folium II (molecular and granular layers) was observed between ANA-EtOH females and AA-EtOH females. Furthermore, the volume of the molecular layer in folium II was significantly (p < 0.05, analysis of covariance with ethanol intake and body weights as covariates) reduced for ANA-EtOH females, compared with ANA-EtOH males indicating a sex difference in the cerebellar degeneration due to chronic alcohol consumption. Of the three layers studied, the white matter layer was the most resistant layer to the effects caused by chronic alcohol consumption. In view of the fact that AA and ANA rats of both sexes differ regarding the drinking behavior and ethanol metabolism, they provide an important model for further research on ethanol-induced pathological changes in the central nervous system.

Acetaldehyde↗
PubMed1997

Ethanol-reinforced responding by AA and ANA rats following the sucrose-substitution initiation procedure.

Ethanol-reinforced responding was initiated in male AA and ANA rats using the sucrose-substitution procedure. Before the initiation procedure, a homecage, two-bottle preference test was conducted. The rats were then trained to respond on an Fixed-Ratio 1 schedule with sucrose reinforcement. Over sessions, ethanol was added gradually to the sucrose solution as the concentration of sucrose was reduced until 10% ethanol (v/v) alone functioned as the reinforcer for lever pressing. The schedule of reinforcement was then increased to Fixed-Ratio 4. Next, the ethanol concentration presented as the reinforcer was increased over weeks to 15%, 20%, 30%, and then returned to 10%. A second homecage test was then performed. The results showed that the AA and ANA lines differed significantly on preference and intake (g/kg) during the homecage preference tests. There was a significant increase in preference during the second homecage test. During sucrose substitution, initial large differences in responding were observed between the lines. When the ethanol concentration was increased, intake (grams per kilogram) increased for the AA line but not for the ANA line. These effects were a function of no change in responding by the AA rats as concentration was increased and a decrease in responding by the ANA rats at the higher concentrations (20% and 30%). Taken together, data indicate that ethanol can function as a positive reinforcer for the behavior of AA and ANA rats. Even though 10% ethanol functioned as a reinforcer similarly for the two lines, ethanol intake in the AA line was significantly greater at the higher concentrations of ethanol, suggesting that ethanol functioned as a qualitatively different reinforcer for the AA rats, compared with the ANA rats.

Alcohol Drinking↗
PubMed1997

Behavioral similarities and differences among alcohol-preferring and -nonpreferring rats: confirmation by factor analysis and extension to additional groups.

Thirteen behavioral variables from six tasks were measured in alcohol-preferring (AA, FH, and P) and -nonpreferring (ANA, FRL, and NP) rat lines/strains and subjected to Factor Analysis. Four Independent factors accounted for > 90% of the variance. Defecation in the open field and ultrasonic vocalizations after an air puff were negatively correlated with alcohol intake and preference, whereas the increase in daily fluid intake in the presence of saccharin was positively correlated. Other factors could be labeled Activity, Emotionality, and immobility Factors, and each was independent of the Alcohol Factor. When an additional alcohol-preferring rat line (HAD) and two additional nonpreferring groups (LAD and ACI) were tested, they were found to differ on most behaviors that were associated with alcohol intake and preference in the Factor Analysis; vocalizations and saccharin-induced increase in fluid intake, but not defection. A new Factor Analysis was then performed incorporating these three new groups and including five new behavioral measures. The following measures had high loadings on the Alcohol Factor: alcohol intake under choice conditions; alcohol preference; forced alcohol intake; alcohol acceptance (forced alcohol intake/basal water intake x 100); ultrasonic vocalization; saccharin intake; saccharin-induced increase in daily fluid intake; defecation in the open field test; and immobility in a modified forced swim test. These findings indicate that there are indeed certain behavioral characteristics that are common among alcohol-preferring rat lines/strains, but there are also substantial group differences on other behavioral measures. For those behavioral measures reflecting emotionality (defecation and ultrasonic vocalization) that loaded highly on the Alcohol Factor, the alcohol-preferring rats had lower scores.

Alcohol Drinking↗
PubMed1996

Effect of prior ethanol experience on dopamine overflow in accumbens of AA and ANA rats.

The purpose of this study was to investigate the effect of repeated ethanol administration on dopamine overflow in the nucleus accumbens of alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Nonalcohol) rats. Dopamine is a possible mediator of the reinforcing effects of ethanol, but it has previously been shown that ethanol-naïve alcohol-preferring AA and alcohol-nonpreferring ANA rats do not differ in their dopaminergic reaction to an intraperitoneal ethanol injection (0.5-2.0 g/kg), as assessed by measuring extracellular dopamine in the nucleus accumbens with in vivo microdialysis. Here a group of AA rats drank 10% (v/v) ethanol voluntarily-continual access for 5-15 days, limited access for 3 weeks-while a yoked group of AA rats and a yoked group of ANA rats received the same amount intragastrically by intubation. The rats were implanted with guide cannulas on the fourth week of limited access. Dopamine overflow was monitored in the microdialysis perfusate after 1 g/kg i.p. ethanol. The AA and the ANA rats that received ethanol non-contingently showed the same dopaminergic response to this as naïve animals have before. The group that had ingested the ethanol voluntarily showed, however, a significantly smaller increase in dopamine after 1 g/kg ethanol i.p. This suggests that the active behavior associated with obtaining the contingent drug may have an important impact on the reactions of the dopamine system to the drug, producing different results than when the same drug is administered by other routes. The hypothesis that dopamine mediates ethanol reinforcement in AA rats is not supported by the results.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Effect of ethanol on extracellular dopamine in the nucleus accumbens of alcohol-preferring AA and alcohol-avoiding ANA rats.

The role of central monoamines in the genetically determined influences on voluntary ethanol consumption were examined by studying the extracellular levels of monoamines in the nucleus accumbens of the alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Nonalcohol) rats with in vivo microdialysis. Dialysate samples for the assay of monoamines with small bore HPLC were collected from freely moving animals at 15 min intervals after administration of ethanol (0.5, 1, or 2 g/kg, i.p.). Ethanol significantly increased the extracellular levels of dopamine, DOPAC, and HVA, suggesting stimulation of dopamine release by ethanol, while the effect on 5-HIAA did not reach significance. No difference in the extent or time course of stimulation of dopamine release between the AA and ANA rats was found. The results could so far give no indication that the differential ethanol consumption by AA and ANA rats could be explained in terms of differences in ethanol-induced stimulation of dopamine release in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Distribution of the mu and delta opioid binding sites in the brain of the alcohol-preferring AA and alcohol-avoiding ANA lines of rats.

There is experimental evidence indicating that the positive reinforcing effects of ethanol, responsible for voluntary ethanol consumption, are in part mediated by the endogenous opioid system. Differences in some components of the endogenous opioid system have been observed between lines and strains of animals bred selectively for their high or low ethanol consumption. Our objective was to investigate the presence of differences in the density and distribution of mu and delta opioid receptors in the brain of the alcohol-preferring Alko-Alcohol and alcohol-avoiding Alko, NonAlcohol lines of rats using iodinated ligands specific for mu ([D-Ala2, MePhe4, Met(o)ol5]-Enkephalin (FK 33-824)) or for delta ([D-Ser2]-leucine enkephalin-Thr) opioid receptors. Results calculated from studies on membrane preparations of whole brain minus cerebellum indicated that the Bmax and Kd were similar between the two lines of rats; however, autoradiographic studies showed that the alko-alcohol rats presented significantly higher density of mu opioid receptors in some brain regions, including nuclei of the limbic system that are important in mediating the reinforcing properties of many drugs of abuse. Furthermore, studies on brain membrane preparations indicated that both lines of rats were deficient in high affinity delta binding sites compared to Sprague-Dawley rats. Indeed, autoradiographic studies confirmed the presence of low density of the high affinity binding sites for [D-Ser2]-leucine enkephalin-Thr in both lines of rats. However, the density of the high affinity delta binding sites was higher in some distinct brain regions of the Alko-Alcohol than Alko-NonAlcohol rats. These differences in the density of both mu and delta opioid receptors may be partially responsible for the differences in voluntary ethanol consumption exhibited by these two lines of rats.

Alcoholism↗
PubMed1994

Spontaneous and ethanol-stimulated in vitro release of beta-endorphin by the hypothalamus of AA and ANA rats.

Previous studies demonstrated that both the spontaneous and ethanol-stimulated release of beta-endorphin (beta-EP) like-peptides (beta-EPLPs) by the hypothalami of the ethanol-preferring C57BL/6 mice is more pronounced than by the hypothalami of the ethanol-avoiding DBA/2 mice. The objective of the present studies was to investigate the effects of various concentrations of ethanol on the in vitro release of beta-EP peptides by the hypothalami of the ethanol-preferring Alko-Alcohol (AA) and ethanol-avoiding Alko Non-Alcohol (ANA) lines of rats. Results indicated that although the spontaneous release of hypothalamic beta-EPLPs was higher by the ANA than by the AA rats, the percentage increase following exposure to various concentrations of ethanol was similar in both lines of rats. Furthermore, the release of hypothalamic beta-EPLPs following exposure to 30 mM ethanol was significantly higher than the release following exposure to 10 mM ethanol in the AA, but not the ANA, rats. Analysis of the released beta-EPLPs with Sephadex G-75 and reversed phase HPLC indicated that the nonacetylated beta-EP 1-31 was the major component in the hypothalamic perifusates of the AA rats, whereas the shorter and acetylated forms of beta-EP were the predominant components in the hypothalamic perifusates of the ANA rats. Because the shorter and acetylated forms of beta-EP are devoid of opioid activity, their pronounced release by the hypothalami of the ANA rats may be important in maintaining their low ethanol consumption, even after long-term access to ethanol solutions.

Alcohol Drinking↗
PubMed1994

Effects of lifelong ethanol consumption on the ultrastructure and lipopigmentation of rat heart.

The myocardial interactions of ageing and lifelong ethanol ingestion were studied in the ethanol-preferring AA (Alko Alcohol) line of rats. Samples of the left ventricle from young control rats (3-month), old control rats (30-month) and rats exposed to ethanol from 3 to 30 months of age, were studied in terms of myocardial ultrastructure and lipopigmentation. Electron microscopic morphometry showed an age-related increase in the volumetric densities of lipofuscin and unspecified sarcoplasm, while the proportions of mitochondria, myofibrils and tubular structures remained unaltered in the left ventricular myocardium. Lifelong ethanol exposure increased the proportion of sarcoplasmic reticulum and transverse tubules, apparently due to dilation of the tubular structures. Mitochondria were significantly larger in the ethanol-exposed rats compared to the control rats of the same age, while the volumetric proportion of mitochondria tended to decrease in the ethanol-exposed group. Fluorescence microscopic image analysis showed that myocardial lipopigmentation (proportion of myocardial area covered by autofluorescent lipopigments) was about two-fold in the old ethanol-exposed rats compared to the old control rats, and 13-fold compared to the young controls. It is concluded that ageing and chronic ethanol ingestion produce rather different patterns of alteration in myocardial ultrastructure, which does not support the concept of ethanol-induced accelerated ageing. The enhancement of myocardial lipofuscin accumulation is thought to reflect chronic oxidative stress in the hearts exposed to ethanol.

Age Factors↗
PubMed1994

Genetically determined influences on voluntary ethanol consumption: extracellular levels of ethanol and monoamines in the nucleus accumbens of the alcohol preferring AA and alcohol avoiding ANA rat lines.

The role of central monoamines and the distribution of ethanol to the brain in the genetically determined influences on voluntary ethanol consumption were examined by studying the extracellular levels of ethanol and monoamines in the nucleus accumbens of the alcohol preferring AA (Alko Alcohol) and alcohol avoiding ANA (Alko Non-Alcohol) rats with in vivo microdialysis. The results show that there is a steep rise in brain ethanol concentration within minutes after the injection of ethanol (1 g/kg ip), but there does not seem to be a difference in the distribution of ethanol into the brain of the two lines of rats. There was, however, some indication that ANA rats may absorb ethanol after intragastric administration faster than AA rats. Ethanol (0.5, 1, or 2 g/kg ip) significantly increased the extracellular levels of dopamine, DOPAC, and HVA, but not that of 5-HIAA, suggesting stimulation of dopamine release by ethanol. No difference in the extent or time course of stimulation of dopamine release between the AA and ANA rats was found.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

[Alcohol consumption and brain adenylate cyclase system in rats: brain adenylate cyclase activity in alcohol-preferring AA and alcohol-avoiding ANA rats].

Brain adenylate cyclase (AC) activity in the alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko, Non-Alcohol) rats was examined. Both basal and Gpp(NH) p-stimulated AC activities were higher in the cerebral cortex of the ANA rats than in the AA rats. Isoproterenol-stimulated AC activity tended to increase in the cerebral cortex of the ANA rats compared to the AA rats. Basal AC activity in the striatum of the AA rats was higher than that in the ANA rats, however, striatal Gpp(NH)p-stimulated AC activity was not different between the two rats lines. In the mesolimbic and cerebellum, there was no difference in AC activity between the rat lines. These results suggest that the noradrenergic function in the cerebral cortex has an important role in the regulation of alcohol intake.

Adenylyl Cyclases↗
PubMed1992

Decreased levels of muscarinic receptors in bladders from the alcohol preferring rat line.

The Bmax for [3H]QNB binding in the bladders of alcohol preferring (AA) rats was only approximately 60% of that in the alcohol non-preferring (ANA) rats. No significant change in Bmax for [3H]QNB binding in bladder was observed between alcohol insensitive (AT) and alcohol sensitive (ANT) rats. No significant change in Kd for [3H]QNB binding in bladder was observed between the four different rat lines studied. Therefore, alcohol preference but not sensitivity is associated with a decrease in muscarinic receptor density in the rat bladder. Because all of the rats used in this study were ethanol-naive, the decrease in muscarinic receptor density in the bladders of alcohol preferring rats is associated with genetic factors inherent to this rat line. Further studies are needed to determine if these observations are tissue specific or specific to the m2 subtype, which predominates in the rat bladder.

Alcohol Drinking↗
PubMed1992

Lifelong ethanol consumption enhances the age-related changes in rat sympathetic neurons.

The effects of aging and chronic ethanol administration on the histochemical and morphometric features of rat superior cervical ganglion were studied in a rat strain selected for voluntary alcohol consumption. Ethanol was administered to the experimental group ad libitum (10% v/v in drinking water) from 3 months to 28 months of age, the average ethanol intake being 6.4-5.4 g/kg per day. The sympathetic neurons of the ethanol consuming rats showed several signs of enhanced degeneration, e.g. decreased neuronal packing density, increased amount of age-pigment and decreased intensity of catecholamine histofluorescence and tyrosine hydroxylase immunoreactivity. The results may indicate a selective vulnerability of peripheral sympathetic neurons rather than a universal accelerated aging due to chronic ethanol exposure.

Aging↗
PubMed1992

Interaction of aging and lifelong ethanol ingestion on ethanol-related behaviors and longevity.

The interactions of aging and long-term voluntary ethanol consumption were studied in the alcohol-preferring AA (Alko Alcohol) rats. The mean daily ethanol intake was 6.45 +/- 0.31 g/kg/day (mean +/- SE) at the beginning of the exposure at 3 months of age. The control animals were given only food and water ad libitum. There was no difference in survival or weight gain between the control and ethanol groups. When tested for voluntary ethanol intake at the age of 24 months, the rats in the ethanol group consumed significantly more ethanol than the controls. The two groups did not differ in ethanol-induced motor impairment, sleep-time, or hypothermia, nor in the rate of ethanol elimination. The 24-month-old animals, however, showed higher sensitivity to ethanol than the 3-4-month-old rats in the sleep-time test. It is concluded that the feeding regimen used in this study did not produce any detectable interactions between ethanol and the aging processes in the AA rats.

Aging↗