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Biomedical subjects

K Kiianmaa

Publications and source records attributed to K Kiianmaa.

At least 55 records · Page 3Linked to original sources
PubMed1992

Differences in the brain and pituitary beta-endorphin system between the alcohol-preferring AA and alcohol-avoiding ANA rats.

The content of pro-opiomelanocortin (POMC) mRNA was determined in the hypothalamus, as well as in the anterior and intermediate lobes of the pituitary gland of the alcohol-preferring AA and alcohol-avoiding ANA rats under basal conditions. In addition the content of beta-endorphin-like immunoreactivity (beta-EPLIR) was measured in nine brain regions, the anterior and intermediate lobes of the pituitary gland and the serum. The content of beta-EPLIR was significantly higher in the septum and significantly lower in the amygdala, and periaqueductal gray matter of the AA rats, while there was no significant difference between the AA and ANA rats in the arcuate nucleus plus median eminence, nucleus accumbens, caudate, hippocampus, and cortex. HPLC analysis indicated no significant differences in the relative proportions of non-acetyl and acetyl forms of beta-endorphin peptides in the hypothalamus, distinct brain regions, and anterior and neurointermediate lobes of the pituitary gland, between the AA and ANA rats. The content of POMC mRNA but not of beta-EPLIR was significantly higher in the hypothalamus and neurointermediate lobe of the AA rats, while the content of both beta-EPLIR and POMC mRNA were significantly higher in the anterior pituitary of the AA than of the ANA rats. Thus, there are genetically determined differences in the pituitary and brain beta-endorphin system between the AA and ANA rats, which may be important in controlling the differences in the voluntary ethanol consumption exhibited by these animals.

Alcohol Drinking↗
PubMed1992

Effect of calcitonin on the alcohol drinking of rats.

Previous work has shown that calcitonin inhibits eating by rats and that it affects several neurotransmitter systems suspected to play a role in alcohol consumption. The present study was an initial test of whether calcitonin does affect voluntary alcohol consumption by male Wistar rats with prolonged alcohol experience. Calcitonin (20 IU/kg) or saline was injected subcutaneously on 10 consecutive days when the rats (n = 20) had continual access to 10% (v/v) ethanol solution, and to food and water. Using a cross-over design, the effects of 40 IU/kg calcitonin vs. saline were then examined in a second 10-day treatment period. Similar patterns of effects were obtained with both calcitonin doses, but the patterns differed with alcohol, food, and water intake. Alcohol drinking showed biphasic changes with both doses, producing highly significant Treatment x Day interactions (p < 1E-10 and p = 6E-7): it was significantly reduced on the first day of calcitonin treatment and significantly increased on the last few days. Food intake was reduced on all calcitonin days although most markedly on the first. Water drinking was not altered on the first calcitonin day, but was greatly increased on the second, then gradually returned toward the baseline. In a second experiment, the animals were switched to 1 hr of alcohol access per day, and calcitonin (20 IU/kg) was administered periodically to one group 4 hr before the alcohol access. Alcohol drinking was significantly reduced in all cases when the calcitonin injection was preceded by at least 1 day without calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1991

Determinants of alcohol preference in the AA and ANA rat lines selected for differential ethanol intake.

A selective breeding program conducted in this laboratory has resulted in the establishment of the alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Nonalcohol) rat lines. These lines have been used as a tool for attempting to identify the behavioral, neurochemical, and biochemical correlates of differential voluntary ethanol consumption. Some of the differences that have been found between the lines involve differential reinforcement: AA rats, but not ANA rats, rapidly acquire an ethanol-reinforced operant response. The AA's greater development of tolerance to the depressant effects of ethanol and their faster ethanol metabolism would also allow them to drink more. Neurochemical studies have suggested differential functioning of brain monoaminergic mechanisms. The activity of tyrosine hydroxylase and dopa decarboxylase, and the brain dopamine concentrations are higher in the AA rats than in the ANA rats, and the maximal number of dopamine D2 receptors is lower in the AA rats. The concentration of noradrenaline is higher in the brain of ANA rats than in that of AA rats, while the 5-hydroxytryptamine levels do not seem to differ greatly. The importance of these differences to the line difference in ethanol intake is not, however, clear, since there appears to be no difference in the sensitivity of monoamine systems of the two lines to ethanol.

Alcohol Drinking↗
PubMed1990

Role of initial sensitivity and genetic factors in the development of tolerance to ethanol in AT and ANT rats.

The role of initial sensitivity and genetic factors in the development of tolerance to ethanol were examined in rats selected for low (AT) and high (ANT) sensitivity to the motor impairment effect of ethanol. Following chronic ethanol treatment (5 g/kg PO, daily for 20 days), the AT and ANT rats acquired tolerance to the motor impairment effect of ethanol at a similar rate. The AT rats, however, acquired tolerance to the hypothermic effect of ethanol at a higher rate than the ANT rats. Such ethanol treatment did not produce any metabolic tolerance to ethanol in these animals. Since there is no difference in the initial response to the hypothermic effect of ethanol between the AT and ANT rats, the observed differences in the rate of tolerance development might be related to a direct genetic factor. The similar rate of tolerance development to the motor impairment effect of ethanol between the two lines was attributed to an interaction between an indirect (initial sensitivity) and a genetic factor in tolerance development.

Animals↗
PubMed1990

Neuronal mechanisms of ethanol sensitivity.

Lesion studies have suggested that different behavioural effects of ethanol are separate behavioural phenomena, caused by specific effects of ethanol on separate and independent neuronal mechanisms. Such a conclusion can also be drawn from behavioural studies showing that the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) rat lines selected for differential ethanol-induced motor impairment, do not differ in all components of ethanol intoxication. Furthermore, neurochemical work has demonstrated differences in the functioning and the sensitivity to ethanol in catecholaminergic and GABAergic mechanisms between the lines, suggesting a role for both of these systems in the control of ethanol-induced motor impairment.

Animals↗
PubMed1990

The alcohol tolerant and alcohol nontolerant rat lines selected for differential sensitivity to ethanol: a tool to study mechanisms of the actions of ethanol.

Genetic selection work conducted in the Research Laboratories of State Alcohol Company (Alko Ltd), Helsinki, Finland, has resulted in the establishment of the ethanol sensitive Alcohol Nontolerant (ANT) and ethanol insensitive Alcohol Tolerant (AT) rat lines which differ in their sensitivity to ethanol induced motor impairment. These lines have been used in attempts to identify the mechanisms controlling ethanol induced motor impairment. The Alcohol Tolerant rats show a lower sensitivity to ethanol induced motor impairment on a tilting plane over a wide range of doses, but the lines do not differ in all behavioral measures of ethanol sensitivity. Furthermore, the Alcohol Tolerant line shows a higher capacity to develop acute tolerance and less calm behaviour, which may contribute to the line difference. Neurochemical work has shown differences in the functioning and sensitivity to ethanol of the catecholaminergic and GABAergic systems in the two lines, suggesting a role for both of these systems in the control of ethanol induced motor impairment.

Alcoholism↗
PubMed1989

The AA and ANA rat lines, selected for differences in voluntary alcohol consumption.

The offspring of rats that voluntarily select larger quantities of alcohol are heavier consumers of alcohol than the offspring of rats that tend to avoid it. Such selective breeding, repeated over many generations, was used to develop the AA (Alko, Alcohol) line of rats which prefer 10% alcohol to water, and the ANA (Alko, Non-Alcohol) line of rats which choose water to the virtual exclusion of alcohol. In addition to demonstrating the likely role of genetic factors in alcohol consumption, these lines have been used to find behavioral, metabolic, and neurochemical correlates of differential alcohol intake. Some of the line differences that have been found involve the reinforcing effects of ethanol, the changes in consumption produced by alcohol deprivation and nutritional factors, the behavioral and adrenal monoamine reactions to mild stress, the development of tolerance, the accumulation of acetaldehyde during ethanol metabolism, and the brain levels of serotonin. It is hoped that these studies will lead to a better understanding of the genetically-determined mechanisms that influence the selection of alcohol.

Alcohol Drinking↗
PubMed1989

GABA turnover in the brain of rat lines developed for differential ethanol-induced motor impairment.

The role of GABAergic neurons in the differential sensitivity to ethanol between the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) rat lines developed for low and high degree of motor impairment from ethanol, was studied by comparing the effect of ethanol (2 or 4 g/kg, IP) on GABA turnover in different regions of the brain in these rat lines. GABA turnover was estimated from the accumulation of GABA after inhibition of GABA aminotransferase with aminooxyacetic acid (AOAA, 50 mg/kg, IP) given 10 min after administration of ethanol. The rats were killed two hours after the AOAA treatment with focused microwaves. The concentrations of GABA, aspartate, glutamate, glutamine and taurine were analyzed with HPLC. The saline-treated ANT rats were found to have a higher concentration of GABA in the striatum and a higher rate of GABA accumulation in the cerebellum than the AT rats. Ethanol suppressed the accumulation of GABA in both lines, but the suppression was significantly greater in the AT rats than in the ANT rats. In specific regions, this line difference was significant in the cerebral cortex and cerebellum with the higher ethanol dose. No line differences were found in the brain or tail blood ethanol concentration. AOAA increased the concentration of glutamine, decreased that of aspartate and glutamate, and did not modify that of taurine. The AOAA-induced changes in the concentrations of these amino acids were, however, minor relative to those found in the concentrations of GABA. The results that GABAergic mechanisms are involved in the differential sensitivity to the motor-impairing effects of ethanol between the AT and ANT rats.

4-Aminobutyrate Transaminase↗
PubMed1989

Effect of GABAergic drugs on motor impairment from ethanol, barbital and lorazepam in rat lines selected for differential sensitivity to ethanol.

The effect of GABAergic drugs on the motor-impairing effects of ethanol, barbital, and lorazepam were studied in the ethanol-sensitive ANT (Alcohol Nontolerant) and ethanol-insensitive AT (Alcohol Tolerant) rat lines, selected for differential ethanol-induced motor impairment on the tilting plane. The basic population from which these rat lines were derived, the mixed (M) line, was also included in the study. The ANT rats were more sensitive to the intoxicating effects of ethanol, barbital, and lorazepam than the AT and M rats at the dose ranges tested. Picrotoxin antagonized motor impairment from all three drugs. Flumazenil (Ro 15-1788) antagonized only the effects of lorazepam, and isoniazid did not modify motor impairment induced by any of the three drugs. These results confirm that the selection of AT and ANT lines has not been specific to ethanol, and that it has increased sensitivity to ethanol, barbital, and lorazepam in the ANT rats rather than decreasing it in the AT rats relative to the M rats. The finding that picrotoxin counteracted motor impairment from ethanol, barbital, and lorazepam support the view that the GABAA receptor complex is important in mediating the intoxicating effects of these drugs. These results also suggest that the genetically-determined difference in sensitivity to ethanol between the rat lines involves GABAergic mechanisms, but it remains to be determined whether any part of the GABAA receptor itself has been affected by the selection program.

Animals↗
PubMed1988

Characteristics of ethanol tolerance in alcohol drinking (AA) and alcohol avoiding (ANA) rats.

The development of tolerance to ethanol was examined in two rat lines selected for high (AA) and low (ANA) ethanol consumption. In the first experiment, the acquisition of tolerance to the motor-impairment, hypothermic and hypnotic effects of ethanol produced by daily treatment with 5 g/kg ethanol for a period of 24 days was examined. Tolerance to these effects of ethanol was observed in the AA rats while marginal or no tolerance was demonstrated in the ANA rats. In the second experiment the development of rapid tolerance to the hypothermic and hypnotic effects of ethanol was examined. The hypothermic and hypnotic responses to IP injection of 3.5 g/kg ethanol were found to be attenuated in the AA but not the ANA rats by a single equivalent ethanol injection given 24 h earlier. These results suggest some relationship between the capacity to develop tolerance and voluntary ethanol intake.

Alcohol Drinking↗
PubMed1988

Effects of ethanol, barbital, and lorazepam on brain monoamines in rat lines selectively outbred for differential sensitivity to ethanol.

The acute effects of ethanol, barbital, and lorazepam on the synthesis and metabolism of brain monoamines were studied in the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) lines of rats, which have been selected for differential motor impairment after ethanol administration. The ethanol-sensitive ANT rats are also more sensitive than the ethanol-insensitive AT rats to the motor impairment caused by barbital and lorazepam. Ethanol increased, whereas barbital and lorazepam decreased, the synthesis of catecholamines in several regions of the brain. Ethanol did not affect the formation of DOPAC, whereas barbital and lorazepam reduced it. Similarly, the accumulation of 5-HTP was increased after administration of ethanol, but was decreased after administration of barbital or lorazepam. Ethanol, barbital and lorazepam decreased the formation of 5-HIAA. The rat lines did not differ in any of these responses. Some differences could, however, be demonstrated between the AT and ANT rats in the effects of the three drugs on the levels of the brain monoamines. Although the importance of these differences in the differential sensitivity to these drugs between the two lines is difficult to determine, the role of central monoaminergic mechanisms cannot be excluded. These findings also suggest that the motor impairment induced by ethanol, barbiturates, and benzodiazepines is probably not primarily based on the monoaminergic systems.

Animals↗
PubMed1987

Neonatal desipramine or zimeldine treatment causes long-lasting changes in brain monoaminergic systems and alcohol related behavior in rats.

To study the relationship between neonatal antidepressant administration, active (REM) sleep and adult alcohol-related behavior, rat pups were treated daily with 5 mg/kg desipramine (DMI) or 25 mg/kg zimeldine SC from the 6th to the 19th postnatal days. Movement sensitive mattress ("SCSB") measurements showed that zimeldine treatment suppressed active sleep throughout the whole treatment period, but DMI was more effective during the first 8 days than during the last treatment days. At the age of 70 days, the zimeldine-treated rats expressed a selective increase of some components of activity in the open field test, and the DMI rats had a higher defecation score compared to the controls. Furthermore, the zimeldine-rats responded with a decrease in ambulation in the open field to an alcohol dose which generally stimulates locomotion in rats. At the age of 3 months the DMI and zimeldine rats showed increased voluntary intake of 10% (v/v) alcohol. Measurement of brain monoamines revealed that the neonatal treatment with DMI or zimeldine interfered with the normal development and function of the monoamine neuronal systems: the concentrations of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), and their metabolites were altered in several brain regions. The results thus suggest that neonatal treatment with DMI or zimeldine suppresses active sleep and has an influence on later alcohol-related behavior, possibly due to a long-lasting defect in brain monoaminergic transmission.

Alcohol Drinking↗
PubMed1987

Intoxicating effects of lorazepam and barbital in rat lines selected for differential sensitivity to ethanol.

The motor impairing effects and plasma concentrations of barbital and lorazepam were studied in the alcohol tolerant (AT) and alcohol non-tolerant (ANT) rat lines developed for low and high sensitivity to motor impairment from ethanol. The mixed (M) line, from which the AT and ANT rats were derived, was also included in the study. Like ethanol, barbital and lorazepam impaired the performance of the ANT rats more than that of the AT rats. The motor performance of the M rats was relatively more impaired after barbital than after lorazepam administration at the same dose used in the AT and ANT rats. At the two latter time points (2.5 and 3.5 h) the sensitive ANT rats had significantly higher serum barbital concentrations than the AT rats. The serum barbital concentrations of the AT and ANT rats did not differ, however, at the two first time points (0.5 and 1.5 h) of the tilting plane tests, although the ANT rats were significantly more intoxicated. The concentrations of lorazepam in plasma do not explain the differential motor impairment either, since the sensitive ANT rats had lower plasma concentrations than the insensitive AT rats. The results, thus, suggest that the selection involved in the development of the AT and ANT lines has not been specific for ethanol. The results also support the idea that ethanol, barbiturates and benzodiazepines have some modes of action in common.

Animals↗
PubMed1987

Role of brain monoaminergic systems in the increased ethanol drinking caused by REM-sleep deprivation.

The central monoaminergic neuronal effects of REM-sleep deprivation, and the effect of different monoamine uptake blocking agents on the REM-sleep deprivation-induced increase in ethanol intake were studied. The levels of 5-HT and 5-HIAA in the hypothalamus were increased both in the REM-sleep deprived rats and the stressed control rats, but the hypothalamic level of MHPG was decreased only in the REM-sleep deprived animals. Two daily injections (5-20 mg/kg/d) of citalopram or GBR-12909 (uptake blocking agents for 5-HT and dopamine, respectively) did not modify the increased level of ethanol intake. The noradrenaline uptake blocking agent, talsupram (5-10 mg/kg/d), however, decreased ethanol intake to the levels seen prior to deprivation. This effect of talsupram could be antagonized by blocking alpha-1-adrenoreceptors with prazosin (1 mg/kg/d).

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Neonatal antidepressant administration suppresses concurrent active (REM) sleep and increases adult alcohol consumption in rats.

Neonatal administration of desipramine, nomifensine and zimeldine suppressed concurrent active sleep and led to increased preference of alcohol as well as decreased concentrations of monoamines in the brain in adult rats. The findings suggest that early postnatal active sleep and the monoaminergic transmission regulating it are related to adult alcohol consumption.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Effects of barbital and lorazepam in the AT and ANT rats: motor performance and brain monoamine functions.

The motor impairing effects and central monoaminergic neuronal effects of barbital (120 mg/kg, IP) and lorazepam (3 mg/kg, IP) were studied in the alcohol tolerant (AT) and alcohol non-tolerant (ANT) rat lines developed for low and high sensitivity to motor impairment from ethanol (2 g/kg, IP), respectively. Like ethanol, both barbital and lorazepam impaired the performance of the ANT rats more than that of the AT rats. Ethanol increased the synthesis of catecholamines in the striatum and hypothalamus, but barbital and also lorazepam decreased it in both rat lines. Ethanol increased or did not modify the synthesis of 5-HT in the cerebral cortex and hypothalamus, while barbital and lorazepam decreased it; the rat lines did not differ in these neuronal effects.

Animals↗
PubMed1987

Studies of a brain polypeptide functioning as a putative endogenous ligand to benzodiazepine recognition sites in rats selectively bred for alcohol related behavior.

The brain content of Diazepam Binding Inhibitor (DBI), its cell location and that of its specific mRNA were studied immunohistochemically and by in situ hybridization. Various strains of rats were genetically selected for their alcohol tolerance and the above mentioned brain parameters were studied before and after chronic ethanol consumption. The DBI like immunoreactivity (DBI-LI) was found to be located in selected neuronal population and in non-neuronal cells. The DBI-mRNA was located in brain areas where DBI is abundant. It was immunochemically determined that the DBI content was increased in cerebellum and in hypothalamus of alcohol preferring rats after chronic ethanol consumption. DBI content was compared in the cerebellum of rats genetically selected for different alcohol sensitivity and it was significantly higher on the ethanol sensitive (ANT) rat strain.

Alcoholism↗