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L Ahtee

Publications and source records attributed to L Ahtee.

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

The fall of homovanillic acid and 5-hydroxyindoleacetic acid concentrations in brains of mice withdrawn from repeated morphine treatment and their restoration by acute morphine administration.

The striatal homovanillic acid (HVA) and cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were estimated in male mice withdrawn from 3- to 5-day morphine treatment (total dose: 1,100-2,350 mg/kg). All mice were given probenecid (200 mg/kg, 2 hours). The HVA concentration was decreased (by 26%) in mice withdrawn from 3-day treatment, but the 5-HIAA concentration fell (by 22%) only after 4-day treatment. An acute morphine dose (30 mg/kg, 2 hours) clearly elevated the HVA concentration in mice withdrawn from 4-day treatment, but mice withdrawn from 3-day treatment tended to be tolerant to the HVA concentration elevating effect of morphine. The acute dose increased the 5-HIAA concentration in mice withdrawn from 4-day treatment, by 20-40%, but the mice withdrawn from 3-day treatment were clearly tolerant to this effect of morphine. These results suggest that endogenous activities of dopaminergic and 5-HTergic neurons are attenuated by repeated morphine treatment. However, such attenuation seems to reactivate these neurons to respond to acute morphine administration nearly normally.

Animals↗
PubMed1987

Effect of neonatal nomifensine exposure on adult behavior and brain monoamines in rats.

The aim of the study was to examine the effects of early postnatal exposure to nomifensine, an inhibitor of catecholamine uptake, on concurrent active (REM) sleep, on later alcohol related behavior and on monoamine concentrations in various brain regions of rats. For these purposes rats were given daily injections of 10 mg/kg nomifensine s.c. between the 7th and the 18th postnatal days. During the nomifensine exposure active sleep, expressed as a percentage of total sleeping time, was reduced. At one month of age, the nomifensine rats showed increased ambulation and had lower defecation scores in the open-field than the controls. Neonatal exposure to nomifensine increased voluntary intake of 10% (v/v) alcohol when the rats were 2-3 months of age. The rats, however, did not exhibit preservation in the T-maze, and similarly to control rats suppressed drinking 0.1 M lithium chloride even when thirsty. Measurement of cerebral monoamine concentrations at the age of 3 months suggested that neonatal nomifensine treatment interferes with the noradrenergic and serotonergic systems in several regions of the brain. Concentrations of noradrenaline and 5-hydroxyindoleacetic acid (5-HIAA) were decreased in the cerebral cortex and frontal cortex, concentration of 5-HIAA was decreased in the neostriatum, and concentrations of noradrenaline, 5-hydroxytryptamine (5-HT) and 5-HIAA were elevated in the lower brain stem. Taken together, these findings show that exposure to nomifensine during the 2nd and 3rd postnatal weeks suppresses neonatal active sleep, causes changes in the adult open-field behavior, and increases voluntary alcohol intake, perhaps due to a long-lasting alteration in brain monoamines.

Aging↗
PubMed1987

Differences in the effects of morphine on the alpha-methyl-p-tyrosine-induced depletion of dopamine and noradrenaline in various areas of the mouse brain.

The effect of morphine on the alpha-methyl-p-tyrosine (alpha MT)-induced depletion of dopamine (DA) and noradrenaline (NA) was studied in various brain areas of male NMRI mice, whose locomotor activity is clearly stimulated by morphine. Morphine (10 mg/kg) accelerated the alpha MT-induced DA depletion in the striatum and in the area "rest of forebrain + midbrain", which contains the limbic dopaminergic neurons, but did not clearly alter it in the hypothalamus. The effects were blocked by naloxone. The enhancement of the striatal DA depletion was attenuated when morphine was given after alpha MT or when morphine dose was increased to 30 mg/kg. The smallest dose of morphine to enhance the alpha MT-induced NA depletion in the forebrain + midbrain area was 3 mg/kg, and in the hypothalamus and the lower brain stem 10 mg/kg. The enhancement of the NA depletion was dose-dependent, occurred whether morphine was given before or after alpha MT, and was blocked by naloxone. Our findings suggest that morphine alters the alpha MT-induced depletion of cerebral DA in mice similarly to what has been reported to occur in rats. In contrast its effects on cerebral NA depletion in mice are clearly different from its effects in rats. The substantial activation of cerebral noradrenergic systems, especially of those in the forebrain + midbrain area, in mice could underly the fact that morphine's predominant behavioural effect in mice is stimulation of motor activity.

Animals↗
PubMed1987

Cerebral monoamine neurotransmitters in opioid withdrawal and dependence.

The functioning of cerebral monoaminergic neurons is altered during withdrawal from morphine. Our results suggest that the functioning of cerebral dopaminergic and possibly 5HTergic neurons might be regulated by opioid mechanisms and these neurons may be important in the reinforcing and rewarding effects of morphine. The limbic dopaminergic neurons seem to be more vulnerable to chronic opioid administration than the striatal ones. The cerebral noradrenergic neurons seem to be linked with physical signs and symptoms of opioid withdrawal.

Brain↗
PubMed1986

The nicotine-induced changes in striatal dopamine metabolism of mice depend on body temperature.

The effects of single and 4 times repeated doses of nicotine on the striatal concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were studied in mice in relation to the nicotine-induced decrease of the body temperature. The single doses of nicotine (0.3, 1, 3 or 10 mg/kg s.c.) increased the DOPAC and HVA concentrations in mouse striatum depending on the dose and the rectal temperature of the mice. The elevations lasted longer and were induced by smaller doses when the decrease of the rectal temperature was prevented by increasing the ambient temperature. At a high ambient temperature (32-34 degrees C) the repeated nicotine doses (4 X 1, 3 or 10 mg/kg s.c.) elevated the striatal DOPAC and HVA concentration. When, however, the hypothermia was not prevented, the repeated doses decreased the striatal HVA concentration and induced less elevation of the striatal DOPAC concentration. It is suggested that nicotine acts on the cholinoceptive receptors regulating striatal dopamine release as it acts on the nicotinic receptors in the autonomic ganglia or in the end-plate regions of the skeletal muscle. Initial activation of the receptors could be followed by a block, which is enhanced by hypothermia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Comparison of central nervous system actions of taurine and N-pivaloyltaurine.

N-Acetyl, N-propionyl, and N-pivaloyl derivatives of taurine were synthesized by applying a modified Schotten-Bauman method starting from taurine and using the corresponding acid chloride or acid anhydride for direct acylation reactions. The central nervous system actions of these lipid soluble taurine derivatives, which were presumed to pass the blood-brain barrier, were studied and compared to those of taurine in mice. A large dose (15 mmol/kg) of intraperitoneally administered taurine lengthened the pentobarbitone induced sleep by 30%. N-Pivaloyltaurine was 45 times more potent but not more effective than taurine. Neither N-acetyl- nor N-propionyltaurine lengthened the pentobarbitone induced sleep in doses up to 3 mmol/kg. Intraperitoneally administered N-pivaloyltaurine depressed the locomotor activity in a smaller dose and for a longer period than taurine. However, when administered intracerebroventricularly neither N-acetyl- nor N-pivaloyltaurine altered the locomotor activity in three times larger dose than in which taurine clearly depressed it. Intraperitoneally administered N-pivaloyltaurine decreased the rectal temperature slightly more than taurine, whereas intracerebroventricularly administered taurine was clearly more potent in inducing hypothermia than its acyl derivatives. Intraperitoneally administered N-pivaloyltaurine was about three times more potent than taurine in increasing the striatal concentration of dopamine. Intraperitoneally administered N-pivaloyltaurine only in a very large dose (3 X 15 mmol/kg) slightly and transiently increased the cerebral taurine concentration. Carboxylesterase inhibition by bis-p-nitrophenyl phosphate (BNPP) did not modify this increase. Furthermore, BNPP pretreatment modified neither the hypothermic nor the striatal dopamine concentration elevating effects of N-pivaloyltaurine. Our results suggest that N-pivaloyltaurine possesses taurine-like pharmacological actions. It is not converted to taurine to produce these actions. When administered intracerebroventricularly it is less potent than taurine. However, when administered intraperitoneally it is more potent than taurine because it seems to pass the blood-brain-barrier more easily than taurine. Thus N-pivaloyltaurine could be used to study the behavioural and other central nervous system actions of taurine.

Animals↗
PubMed1984

Acceleration of cerebral noradrenaline turnover after morphine withdrawal and its retardation by acute morphine administration in rats.

To clarify the effects of withdrawal from chronic morphine treatment on cerebral noradrenaline (NA) turnover, we have measured the alpha-methyl-p-tyrosine (alpha MT)-induced depletion of NA in five brain areas of male Wistar rats given morphine twice daily for 40 or 60 days. After the last morphine dose (50 or 70 mg/kg) the rats were withdrawn for 1, 2 or 4 days. In order to study the development of tolerance a challenge dose of 10 mg/kg of morphine was given to some of the rats. Withdrawal of morphine accelerated the alpha MT-induced NA depletion clearly in the hemispheres and the lower brain stem and slightly in the diencephalon. The acceleration was more pronounced in the brains of rats treated for 60 days than of those treated for 40 days. In the hemispheres the acceleration of NA depletion occurred at 1 and 2 days, in the diencephalon at 2 days, and in the lower brain stem at 2 and 4 days after morphine withdrawal. The most pronounced acceleration of NA depletion coincided with the maximum withdrawal-induced weight loss. The challenge dose of morphine clearly retarded the alpha MT-induced NA depletion in the hemispheres of control rats treated chronically with saline. This retardation was even more pronounced in rats withdrawn from chronic morphine treatment for 1 or 2 days. The challenge dose slightly accelerated the alpha MT-induced NA depletion in the lower brain stem of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Retardation of cerebral dopamine turnover after morphine withdrawal and its enhanced acceleration by acute morphine administration in rats.

To clarify the effects of withdrawal from chronic morphine treatment on cerebral dopamine (DA) turnover, we have measured the alpha-methyl-p-tyrosine (alpha MT)-induced depletion of DA in five brain areas of male Wistar rats given morphine twice daily for 40 or 60 days. After the last morphine dose (50 or 70 mg/kg) the rats were withdrawn for 1, 2 or 4 days. In order to study the development of tolerance some of the rats were challenged with 10 mg/kg of morphine. Withdrawal of morphine retarded the alpha MT-induced DA depletion in the limbic forebrain and after long enough chronic treatment in the striatum, too. The challenge dose of morphine accelerated the cerebral DA depletion slightly less in rats withdrawn for 1 day from 60-day chronic morphine treatment than in rats treated chronically with saline, but it enhanced the DA depletion more in rats withdrawn from morphine for 2 and 4 days than in chronic saline rats. This enhancement was clearest in rats withdrawn for 4 days from 60-day treatment. Thus withdrawal from morphine seems to sensitize the rats to the DA depletion accelerating effect of morphine. Our results show that repeated administration of morphine creates no marked tolerance to the DA depletion accelerating effect of morphine. In contrast, the dopaminergic neurones of the chronically treated rats seem to depend on continuous morphine administration for their normal functioning. Furthermore, the retarded DA turnover after discontinuation of morphine treatment seems to sensitize the dopaminergic neurones to the DA depletion accelerating effect of morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Cerebral dopamine and noradrenaline turnover and effects of morphine test dose in rats withdrawn from 20 days' morphine treatment.

Depletion of dopamine (DA) and noradrenaline (NA) induced by alpha-methyl-p-tyrosine (alpha MT) was studied in five different brain areas of rats withdrawn from 20 days' chronic treatment for 0.5, 1, 2, 3, 4 or 6 days. Some of the alpha MT-treated rats were given a challenge dose of morphine (10 mg/kg) 2.5 h before decapitation. The depletion of DA was clearly retarded in the limbic forebrain but not in the striatum of rats withdrawn from morphine for 1 and 2 days, whereas the alpha MT-induced NA depletion was slightly accelerated in the hemispheres but not in any other part of the brain of rats withdrawn for 1 day. The morphine challenge dose accelerated DA depletion slightly more in limbic forebrain and striatum of chronic morphine rats than of control rats. The challenge dose clearly retarded the NA depletion in all brain parts in rats withdrawn from morphine for 1 and 2 days. This retardation was most pronounced in the hemispheres. In control rats, too, the challenge dose tended to retard the NA depletion in the hemispheres although it enhanced it in the lower brain stem. Our results suggest that the DA neurons in the limbic forebrain and NA neurons in the hemispheres are the catecholamine neurons most readily affected by chronic morphine treatment. In both groups of neurons the alterations were clearest when withdrawal-induced weight loss was most evident.

Animals↗
PubMed1980

Chronic ethanol administration decreases 5-HT and increases 5-HIAA concentration in rat brain.

The effect of acute and chronic ethanol administration on cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations of male Sprague-Dawley and Wistar rats was studied. Acute HIAA concentration one hour after administration. In chronically treated rats the whole brain 5-HT concentration was decreased by 9% during ethanol intoxication. This fall was significant in the part of brain containing diencephalon, mesencephalon and telencephalon except cortex (by 23%; P less than 0.01) and in that containing pons and medulla oblongata (by 37%; P less than 0.001) but not in cerebral cortex. The cerebral 5-HIAA concentrations of chronically treated Wistar and Sprague-Dawley rats were increased during intoxication (4--6 hrs after last ethanol administration) and even more during withdrawal (16--18 hrs after last ethanol administration, by 24--58%; P less than 0.05--0.01). The increase was observed in all three parts into which the brain of Wistar rats were dissected. Because ethanol did not further increase the probenecid induced elevation of cerebral 5-HIAA concentration, our results suggest that ethanol increases the cerebral 5-HIAA concentration by attenuating its removal from the brain.

Animals↗
PubMed1980

Chronic morphine administration decreases 5-hydroxytryptamine and 2-hydroxyindoleacetic acid content in the brain of rats.

To study the effects of chronic morphine treatment on cerebral 5-hydroxytryptamine (5HT) metabolism morphine was administered twice daily for 5 or 8 weeks to male Wistar rats. Control rats were treated with 0.9% NaCl solution for the same period. In rats treated chronically with morphine for 8 weeks the cerebral concentrations of 5HT and 5HIAA were reduced by 12--15% (P less than 0.05) at 26--28 h after the last morphine injection (50 mg/kg s.c.). No such decrease was found in the brain of rats treated with morphine for 5 weeks. A test dose of morphine (30 mg/kg s.c. 2h) increased the cerebral concentration and probenecid-induced accumulation of 5HIAA in the rats treated with morphine for 8 weeks almost as much as in the brain of the control rats. Naloxone (10 mg/kg s.c. 2h) did not cause clear changes in the cerebral 5HT or 5HIAA concentration. These experiments suggest that endogenous opioid mechanisms are concerned in the regulation of 5HT neurons and that prolonged morphine treatment weakens these mechanisms. This weakening of endogenous regulation of 5HT neurons, which, however, still respond to acute morphine administration, might be part of the mechanism of compulsive drug use in narcotic addiction. It is possible that these neurons in dependent individuals do not function optimally without exogenous morphine. A similar phenomenon--weakening of endogenous regulation combined with clear responsivity to exogenous opiates--occurs in the cerebral dopamine neurons of rats treated chronically with narcotic analgesics.

Animals↗