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Biomedical subjects

K Kiianmaa

Publications and source records attributed to K Kiianmaa.

At least 73 records · Page 4Linked to original sources
PubMed1987

Effect of prenatal alcohol exposure on neonatal sleep-wake behaviour and adult alcohol consumption in the AA and ANA rat lines.

To study the role of genetic factors in the effects of prenatal alcohol exposure on behaviour, dams of two rat lines developed to differ in voluntary alcohol intake, alcohol-preferring (AA) and alcohol-avoiding (ANA) rats were given a 5-10% alcohol solution mixed with a 1% sucrose solution as a sole drinking liquid throughout gestation. Sleep-wake behaviour of the offspring was studied at the ages of 7, 14 and 20 days, using a movement-sensitive mattress. In ANA rats, sleep recordings showed that prenatal alcohol exposure increased the percentage of waking but decreased the percentage of active sleep. Sleep-wake behaviour of the AA rats was not affected by alcohol exposure in utero. Prenatal alcohol exposure did not change open field behaviour in 1 month old rats, except that the alcohol-exposed AA rats' defaecation was decreased. When rats were 3 months old, voluntary intake of 10% (v/v) alcohol increased for alcohol-exposed ANA rats and decreased for alcohol-exposed AA rats as compared to the controls. The results indicate that AA rats may compensate for the effects of prenatal alcohol exposure on behaviour, whereas offspring of the alcohol-exposed ANA dams suffer from severe behavioural disturbances. These findings further suggest that genetic factors are responsible for the differences in the susceptibility of rat foetuses to alcohol-induced long-term effects on behaviour.

Alcohol Drinking↗
PubMed1987

Effect of chronic ethanol administration and abstinence on serum thyroid-stimulating hormone, prolactin and growth hormone concentrations in rats with high and low ethanol intake.

Serum anterior pituitary hormone levels of genetically selected AA and ANA rats of Wistar origin as well as those of experimentally selected heavy drinkers (HD) and light drinkers (LD) among normal Wistar rats were studied. AA and HD rats consumed high doses while ANA and LD rats preferred low doses of ethanol. Serum thyroid-stimulating hormone (TSH), prolactin and growth hormone (GH) concentrations were measured by specific radio-immuno-assays before chronic ethanol administration, during physical dependence and on subsequent withdrawal. Basal TSH levels and TSH responses to cold were as a rule decreased in the course of ethanol intake and abstinence, whereas the TRH-induced TSH elevation became more consistent than before ethanol. There was no difference in basal prolactin levels between ethanol preferring and non-preferring rats at abstinence, whereas 30 min cold-exposure seemed to decrease them in HD and LD rats. The high prolactin levels before ethanol and during physical dependence appear to be caused by stress factors involved in the blood collecting procedure. GH levels were not significantly different in ANA, AA, LD and HD rats and neither ethanol intake nor subsequent withdrawal consistently modified GH levels. It is concluded that the observed minor alterations in the levels of anterior pituitary hormones hardly play any significant role in the development of alcohol dependence.

Alcohol Drinking↗
PubMed1986

5-Hydroxyindoleacetic acid and 5-hydroxytryptophol levels in rat brain: effects of ethanol, pyrazole, cyanamide and disulfiram treatment.

The two serotonin metabolites 5-hydroxyindoleacetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL) were measured in two regions of rat brain (pons medulla and diencephalon) using a gas chromatographic-mass spectrometric (GC-MS) method. Acute ethanol intoxication effected an elevation of 5-hydroxytryptophol levels, while 1 week of treatment with ethanol appeared to have no effect on either metabolite when measured 24 h after the last dose. Disulfiram and cyanamide treatment produced an approximately 2-fold increase in 5-hydroxytryptophol and a slight reduction in 5-hydroxyindole-acetic acid. Pyrazole treatment produced an increase in both metabolites. This effect was, however, counteracted by the simultaneous administration of ethanol.

Animals↗
PubMed1986

[Effect of a single ethanol administration on the permeability of the hemato-encephalic barrier for 14C-tyrosine, 14C-DOPA and horseradish peroxidase].

Single injection of ethanol at a dose of 2 and 4 g/kg has been shown to increase blood-brain barrier penetration for peripherally administered 14C-tyrosine and 14C-DOPA. No changes in blood-brain barrier penetration for horseradish peroxidase has been found. Acute effect of ethanol on blood-brain barrier systems of specific and nonspecific transport is discussed.

Animals↗
PubMed1986

[Effect of chronic administration of ethanol on the blood-brain barrier permeability of 14C-tyrosine and horseradish peroxidase in rats].

Chronic 10-days oral ethanol administration in doses 8-11 g/kg per day has been shown to increase blood-brain barrier penetration for peripherally administered 14C-tyrosine in Wistar heavy- and light-drinker rats. No changes in BBB permeability for horseradish peroxidase has been found. Chronic effect of ethanol on BBB systems of specific and unspecific transport in rats heavy- and light-drinkers is discussed.

Alcoholism↗
PubMed1983

Antagonism of the behavioral effects of ethanol by naltrexone in BALB/c, C57BL/6, and DBA/2 mice.

The effects of naltrexone on the increase in locomotor activity induced by a low dose (1.35 g/kg IP) of ethanol and on the duration of loss of righting reflex after a high dose (3.5 g/kg) of ethanol were studied in BALB/c, DBA/2, and C57BL/6 mice. Ethanol increased locomotor activity in DBA and BALB mice, but not in C57BL mice. Naltrexone, at a dose of 0.1 mg/kg, antagonized the ethanol-induced increase in locomotion similarly in DBA and BALB mice. The duration of loss of righting reflex was, however, differentially affected in all three strains by naltrexone. The BALB mice affected in all three strains by naltrexone. The BALB mice were the most sensitive strain (1 mg/kg naltrexone significantly counteracted ethanol hypnosis), the C57BL mice were intermediate (8 mg/kg naltrexone required to antagonize this effect of ethanol), and the DBA mice were least sensitive (no effect evident even at the highest dose of 8 mg/kg) to naltrexone. Thus, naltrexone could antagonize the behavioral effects of a low and high dose of ethanol, but the three strains, which differ in their behavioral response to ethanol, also were differentially sensitive to the effect of naltrexone in reversing ethanol-induced hypnosis and ethanol-induced changes in locomotor activity.

Animals↗
PubMed1983

The activity of monoamine oxidase -A and -B in brains from chronic alcoholics.

The activity of monoamine oxidase--A was found to be lower in homogenates of hypothalamus and caudate nucleus, but not in cortex of the gyrus cinguli and hippocampus, from chronic alcoholics with respect to homogenates from autopsy cases without histories of alcohol abuse. The activity of monoamine oxidase--B was also lower in the alcoholics, but this could be due to the selective effect of age upon this enzyme form, since the alcoholics were younger than controls. No difference was found for either monoamine oxidase -A or -B activities in brain homogenates from an alcohol preferring (AA) strain of rats, with respect to those from a water preferring (ANA) strain.

Aged↗
PubMed1983

Neurochemical correlates of tolerance and strain differences in the neurochemical effects of ethanol.

The behavioral and neurochemical effects of acute and chronic ethanol administration were studied in BALB/c, C57B1/6 and DBA/2 mice. The rates of dopamine synthesis and release in the striatum were estimated by measuring the accumulation of DOPA and DOPAC, respectively, after inhibition of aromatic amino acid decarboxylase with NSD-1024. Biphasic behavioral effects were found in BALB/c and DBA/2 mice, but not in C57B1/6 mice, with low doses of ethanol producing activation and high doses, depression. Biphasic effects were also found in the dopamine response to acute doses of ethanol. The BALB/c and DBA/2 mice showed larger suppressions of DA release in the lower dose ranges of ethanol, and smaller increases at the higher doses than did the C57B1/6 mice. Ethanol stimulated dopamine synthesis in a monophasic, dose-dependent manner, and C57B1/6 mice were less sensitive to this effect of ethanol compared to the other tested strains of mice. Chronic ethanol feeding produced behavioral tolerance to the high-dose depressant effects of ethanol, but not to the low-dose activating effects. Similarly, tolerance developed in the dopaminergic responses to a higher challenge dose of ethanol (3.5 g/kg). These findings demonstrate that genetically determined differences exist in the sensitivity of the dopaminergic systems of mice to ethanol, and suggest that central dopamine neurons may be important in the behavioral effects of ethanol.

Alcoholic Intoxication↗
PubMed1982

Does tolerance develop to the activating, as well as the depressant, effects of ethanol?

Genetically determined differences were demonstrated in the response of mice to low doses of ethanol. Ethanol (1.35 g/kg) produced an increase in locomotion in DBA/2 and BALB/c mice, but did not alter the locomotor activity of C57B1/6 mice. Chronic administration of ethanol produced tolerance to the sedative/hypnotic effects of high doses of ethanol in DBA/2 and BALB/c mice, but the equivalent chronic ethanol administration paradigm produced no tolerance to the activating effects of ethanol in these animals. C57B1/6 mice became tolerant to the hypnotic effects of ethanol, but no change in the behavior of these mice, given a low dose of ethanol, was noted after the mice were withdrawn from chronic feeding with ethanol-containing diets. The results indicate the presence of different mechanisms for tolerance development to the activating and depressant effects of ethanol, and indicate that strain-dependent differences in the activating effects of ethanol are not determined by an animal's greater sensitivity to the sedating effects of this drug.

Animals↗
PubMed1980

Alcohol intake and ethanol intoxication in the rate: effect of a 6-OHDA-induced lesion of the ascending noradrenaline pathways.

The ascending noradrenaline (NA) pathways were lesioned by injecting 6-hydroxydopamine (6-OHDA) 16 micrograms/4 microliters bilaterally into the posterior mesencephalon in male Long Evans rats. Another group of rats was pretreated with protriptyline (25 mg/kg), a NA uptake blocking agent, 15 min before they received the intracerebral injections of 6-OHDA. The controls received the vehicle only. Spectrofluorimetric determination of the catecholamine concentrations in various parts of the brain revealed a marked degeneration of the ascending NA systems in the group receiving 6-OHDA. Unexpectedly, the DA systems were also affected by the 6-OHDA treatments. Three weeks after the operation the 6-OHDA group showed a transient increase in ethanol intake. In the tilting-plane test, ethanol (2 g/kg. i.p.) impaired the performance of the 6-OHDA-treated rats significantly more than that of the controls. In contrast, the hypothermic effect of ethanol (4 g/kg, i.p.) was significantly smaller in the lesioned rats. Furthermore, the catecholamine levels in various parts of the brain could be significantly correlated with both the extent of ethanol intoxication and the hypothermia. However, the duration of ethanol-induced narcosis (4 g/kg, i.p.) was affected by the present treatments. These results give further support for the view that the central NA neurons are important in the control of ethanol intake, and that they are involved in the expression of the acute effects of ethanol administration.

Alcohol Drinking↗
PubMed1979

Alcohol intake, ethanol-induced narcosis and intoxication in rats following neonatal 6-hydroxydopamine or 5, 7-dihydroxytryptamine treatment.

Newborn rats were treated with 5,7-dihydroxytryptamine (5,7-HT; 2 x 100 mg/kg s.c., 24 h interval) after pretreatment with desipramine (20 mg/kg s.c.) for depletion of brain 5-hydroxytryptamine (5-HT) or with 6-hydroxydopamine (6-OHDA; 3 x 100 mg/kg s.c., 24 h interval) for selective reduction of brain noradrenaline (NA). The 5,7-HT treatment resulted in a 53% reduction in endogenous 5-HT in the cerebral cortex and a 60% increase in the pons-medulla when determined in adult rats. The 5-HT content in the midbrain was not affected. Endogenous NA in the 6-OHDA treated animals was selectively reduced by 100% in the cerebral cortex, 35% in the midbrain and increased by 117% in the pons-medulla. No difference was found between the voluntary ethanol selection of these groups and that of the controls when measured at the age of 3 months. In a tilting-plane test, ethanol (2 g/kg i.p.) impaired the performance of the 6-OHDA treated rats significantly more than that of the controls. Moreover ethanol (4 g/kg e.p.) produced significantly longer narcosis in these rats. In contrast, the 5,7-HT treated rats were not affected significantly more than the controls in these tests. These results suggest that catecholamine neuronal systems interact with the expression of alcohol intoxication.

5,7-Dihydroxytryptamine↗
PubMed1979

On the role of ascending dopamine systems in the control of voluntary ethanol intake and ethanol intoxication.

Selective lesions of the ascending dopamine pathways were made by bilateral injection of the neurotoxin 6-OHDA (8 micrograms/4 microliters). Catecholamine fluorescence histochemistry revealed a marked degeneration of the ascending mesostriatal and mesolimbic dopamine systems, while the hypothalamic dopamine and noradrenaline nerve terminals were unaffected. After recovery of feeding and drinking behaviors the voluntary ethanol intake was not different from that of the controls. The time of ethanol-induced narcosis and the extent of ethanol-induced hypothermia were not affected. In contrast, in a tilting-plane test conducted two months after the operation, ethanol impaired the performance of the 6-OHDA-treated rats significantly less than that of the controls. This finding suggests a role for the ascending dopamine neurons to the forebrain in the intoxicating effect of ethanol.

Alcohol Drinking↗
PubMed1978

Decreased intoxicating effect of ethanol in rats after 6-hydroxydopamine-induced degeneration of ascending dopamine pathways.

Selective lesion of ascending dopamine pathways was made by injecting the neurotoxin 6-OHDA (8 microgram/4 microliter) bilaterally close to the nigro-striatal dopamine pathway of 18 male Long Evans rats. Similar injections of the vehicle were given to 10 control rats. Two months after the operation intoxication was measured in a tilting-plane test after an injection of ethanol (2 g/kg, IP). Ethanol impaired the performance of the 6-OHDA-treated rats significantly less than that of the controls. This finding suggests a role for the central dopamine neurons in the intoxicating effect of ethanol.

Alcoholic Intoxication↗
PubMed1976

Alcohol intake in the rat after lowering brain 5-hydroxtryptamine content by electrolytic midbrain raphé lesions, 5, 6-dihydroxytryptamine or p-chlorophenylalanine.

Voluntary alcohol consumption was measured in male albino rats after selectively lowering their brain 5-hydroxytryptamine concentration (an AA strain of rats was used, selectively outbred for its high alcohol consumption). The brain 5-hydroxytryptamine concentration was reduced using three different techniques: electrocoagulation of the dorsal and median raphé nuclei of the midbrain; injection of 75 mug of 5,6-dihydroxytryptamine into the lateral cerebral ventricle; and oral administration of 300 mg/kg/day p-chlorophenylalanine as a 0.5 per cent carboxymethylcellulose suspension, for 12 days. The first two methods did not markedly affect alcohol consumption despite a sizable decrease in the brain 5-hydroxytryptamine level: 69 per cent in the raphé-lesioned group and 31 per cent in the 5,6-dihydroxytryptamine-treated group. Intraperitoneal injection of 50 mg/kg L-5-hydroxytryptophan on five successive days resulted in a non-significant decrease in alcohol consumption by the 5,6-dihydroxytryptamine-treated rats. p-Chlorophenylalanine did reduce significantly alcohol drinking but it had a greater effect in increasing water intake, producing a net rise in total fluid consumption. The reduction in alcohol consumption, therefore, was probably an indirect result of the treatment. These findings raise doubts about the previously suggested relationships between brain serotonin depletion and alcohol drinking.

5,6-Dihydroxytryptamine↗