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L Ahtee

Publications and source records attributed to L Ahtee.

At least 19 recordsLinked to original sources
PubMed1994

Morphine-stimulated metabolism of striatal and limbic dopamine is dissimilarly sensitized in rats upon withdrawal from chronic morphine treatment.

The effects of acute morphine on the release of dopamine (DA) in the striatum and limbic forebrain of rats upon 48 h withdrawal from 20-day morphine treatment were studied using 3-methoxytyramine (3-MT) in tissue as an index of DA release. Homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were also measured. The chronic morphine treatment did not alter the concentrations of DA metabolites. Acute morphine (10 mg/kg) elevated all three DA metabolites in both brain areas. Morphine withdrawal potentiated the elevation of striatal and limbic 3-MT as well as that of striatal but not limbic HVA. These findings show that both striatal and limbic DA mechanisms are sensitized to morphine upon withdrawal but that sensitization of DA metabolism in these two brain areas occurs differently.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Effects of taurine, homotaurine and GABA on hypothalamic and striatal dopamine metabolism.

To elucidate the effects of taurine on hypothalamic and striatal dopaminergic neurotransmission we compared its effects to those of gamma-aminobutyric acid (GABA) and homotaurine (a GABAA-receptor agonist) on hypothalamic and striatal concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and, in the case of striatum, 3-methoxytyramine (3-MT) in rats. In addition, hypothalamic and striatal 5-hydroxytryptamine (5-HT) und 5-hydroxyindoleacetic acid, hypothalamic noradrenaline (NA) and 3-methoxy-4-hydroxyphenylglycol sulfate, and pituitary DA concentrations were also measured. The amino acids were injected into the lateral brain ventricles of conscious male rats in doses of 10 and 36 mumol/rat, and rat were sacrificed 15 and 60 min later, respectively. Homotaurine (by 11%) but not the other two amino acids elevated striatal DA, whereas hypothalamic DA was increased by both taurine (36%) and homotaurine (31%). All three amino acids at 36 mumol elevated striatal DOPAC, homotaurine (51%) more than taurine (31%) or GABA (30%), and hypothalamic DOPAC, both taurine (102%) and homotaurine (82%) clearly more than GABA (34%). Neither striatal nor hypothalamic HVA was altered by any of the amino acids. At 10 mumol the amino acids decreased striatal 3-MT by about 40%. At 36 mumol taurine and homotaurine reduced 3-MT by about 70%, whereas increasing the dose of GABA did not further reduce 3-MT. Both taurine and homotaurine at 36 mumol decreased hypothalamic NA content. Neither hypothalamic nor striatal 5-HT metabolism was altered. In the neurointermediate lobe of the pituitary gland taurine at 10 mumol but not at 36 mumol slightly (20%) increased DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Chronic nicotine treatment changes differentially the effects of acute nicotine on the three main dopamine metabolites in mouse striatum.

The effect of chronic treatment with nicotine on striatal dopamine metabolism was studied in mice by measuring the striatal concentrations of dopamine and its metabolites 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). (-)-Nicotine was administered for 7 days using subcutaneously implanted nicotine releasing reservoirs. The release of nicotine was confirmed by measuring nicotine and cotinine concentrations in the plasma. To study the possible tolerance induced by chronic nicotine treatment, acute challenge doses of (-)-nicotine (either 3 mg/kg given once or 1 mg/kg repeated 4 times at 30 min intervals) were given to mice on the 7th day after the implantation. At an ambient temperature of 20-22 degrees C, acute nicotine treatment induced marked hypothermia (-5.2 to -6.7 degrees C) in both chronic nicotine treated and control mice, an effect that was prevented by elevating the ambient temperature to 32-34 degrees C. Chronic nicotine treatment did not per se alter striatal dopamine metabolism. Acute nicotine administration altered the striatal dopamine metabolism in a temperature-dependent manner. In mice kept at 20-22 degrees C, the DOPAC concentration rose slightly but concentrations of 3-MT and HVA fell, indicating a decrease in the release of dopamine. In contrast, in mice kept at 32-34 degrees C the DOPAC and HVA concentrations were clearly elevated by acute nicotine, whereas the concentration of 3-MT was not altered. In these normothermic mice chronic nicotine pretreatment did not alter the effects induced by acutely administered nicotine.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Augmentation of morphine-induced changes in brain monoamine metabolism after chronic naltrexone treatment.

To investigate the role of opioid mechanisms in the regulation of cerebral monoaminergic neurons, male Wistar rats were continuously infused with naltrexone via an Alzet osmotic minipump, or were sham-implanted, for 14 days. Twenty-four hours after removal of the pumps or sham implants, the rats were given s.c. morphine (3, 10 or 30 mg/kg) or saline and were sacrificed 2 hr postinjection. Eight brain regions were assayed for dopamine, 5-hydroxytryptamine, noradrenaline and their respective metabolites. Chronic naltrexone treatment per se caused only small changes in cerebral monoamines. Morphine elevated dose-dependently the cerebral concentrations of the acidic dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, as well as that of the 5-hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid, and that of the noradrenaline metabolite, free 3-methoxy-4-hydroxyphenylethyleneglycol. In naltrexone-pretreated rats these elevations were significantly larger. Furthermore, in the naltrexone-pretreated rats 10 mg/kg of morphine significantly decreased the concentration of the dopamine metabolite 3-methoxytyramine both in the striatum and in the limbic forebrain, whereas in the control rats the 3-methoxytyramine content fell first after the 30-mg/kg dose and only in the striatum. Thus, both the stimulatory and the inhibitory effects of morphine on cerebral monoaminergic neurons seem to be potentiated by chronic naltrexone treatment. These data suggest that the activity of cerebral monoaminergic systems is to some degree regulated by an endogenous opioid input. When that input is chronically blocked, the basal metabolism of monoamines is not much altered but the systems' responsiveness to agonist challenge is increased.

Animals↗
PubMed1989

Comparison of the effects of intraventricular taurine, GABA and homotaurine on serum prolactin levels in male rats.

The effects of taurine (2-aminoethanesulphonic acid), gamma-aminobutyric acid (GABA) and homotaurine (3-aminopropanesulphonic acid), a structural analogue of both taurine and GABA, on serum prolactin (PRL) levels were compared in conscious, unrestrained male rats. Taurine, injected into the lateral brain ventricles at doses of 6 and 10 mumol per rat, elevated serum PRL level by 52% (P less than 0.01) and 90% (P less than 0.001), respectively. GABA elevated serum PRL level (41%, P less than 0.05) only at the lowest dose (1 mumol) tested. Homotaurine was the most effective compound, eliciting increases of 353% and 449% (P less than 0.001) at 6 and 10 mumol per rat, respectively. The rank order of the three amino acids in elevating serum PRL level bears some similarity to their known rank order of potency in altering cerebral dopamine metabolism.

Animals↗
PubMed1989

Changes in brain monoamine metabolism during withdrawal from chronic oral self-administration of morphine and in response to a morphine challenge in the withdrawn state.

Although p.o. self-administration of morphine is a reliable and convenient means of inducing physical dependence, its effects on brain monoamine metabolism have not been determined. Accordingly, in the present experiment young Wistar rats drank increasing concentrations (0.1-0.5 mg/ml) of morphine in water, or water alone, for 37 days. Half the rats in each group were challenged with morphine (10 mg/kg s.c.) when 27 to 29 hr withdrawn, and half with saline. Rats were sacrificed 2 hr postinjection. Seven brain regions were analyzed for noradrenaline (NA), dopamine (DA), or 5-hydroxytryptamine (5-HT), and their respective metabolites. In all cases in which a comparison could be made with prior work utilizing repeated injections to produce dependence, the p.o. regimen produced the same effects. Thus, the mode of administration does not seem to modify the response of monoaminergic neurons to chronic morphine. In withdrawal, NA turnover increased but DA and 5-HT turnovers decreased. Acute morphine accelerated the turnover of all three monoamines. The NA response was attenuated in some brain regions of withdrawn rats, indicating the development of tolerance to the turnover-enhancing effect of acute morphine in noradrenergic neurons. In contrast, the effect of acute morphine on cerebral 5-HT turnover was not altered, and its effect on cerebral DA turnover was enhanced in withdrawn rats. Our results suggest that there are fundamental differences among the three monoaminergic systems in their capacities for adapting to chronic morphine treatment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Antagonism of the nicotine-induced changes of the striatal dopamine metabolism in mice by mecamylamine and pempidine.

The ability of nicotinic receptor blockers, mecamylamine and pempidine, to antagonize the changes in striatal dopamine (DA) metabolism induced by repeated nicotine administration was studied. The contents of DA and its metabolites 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. Mice kept at 20-22 degrees C were given nicotine, 3 mg/kg, s.c., four times, at 30 min intervals, and sacrificed 20 min after the last dose. Hexamethonium, 10 mg/kg, i.p., was administered at 30 min before the first nicotine dose in order to prevent the peripheral effects of nicotine. Mecamylamine, 0.6 or 10 mg/kg, i.p., and pempidine, 0.6 or 20 mg/kg, i.p., were given at 60 min before sacrifice. Mecamylamine and pempidine decreased clearly the striatal 3-MT content, which suggests that the nigrostriatal dopaminergic neurons are physiologically controlled by a stimulatory nicotinic mechanism. The repeatedly administered nicotine caused deep hypothermia, and increased the striatal DOPAC content but decreased the 3-MT and HVA contents. The small dose of mecamylamine, which was the only dose found to effectively antagonize the nicotine-induced hypothermia, antagonized the decrease of HVA content. The large but not the small doses of mecamylamine and pempidine antagonized the nicotine-induced increase of DOPAC content but none of the doses studied antagonized the decrease of 3-MT content. Thus it seems that nicotine decreases the 3-MT content by a mechanism distinct from the mechanism mediating the increase of the DOPAC content. The decreased 3-MT content most probably results from desensitization of nicotinic cholinergic receptors (nAChR) and following decrease of cholinergic regulation of nigrostriatal dopaminergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Comparative studies on the dependence liability of morphine hydrochloride, codeine phosphate and two novel antitussive compounds vadocaine hydrochloride and N-(2',4'-dimethyl-6'-methoxyphenyl)-4-(diethylamine) butanamide hydrochloride in mice.

The effects of two novel antitussive compounds, vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) and N-(2,4-dimethyl-6-methoxyphenyl)-4-(diethylamine)butanamide hydrochloride (OR K-269-HCl) on the suppression of withdrawal signs (hypothermia and weight loss) induced by repeated morphine administration were compared to those of acute morphine and codeine administrations. Moreover, spontaneous and precipitated withdrawal-induced hypothermia, weight loss and behavioural changes from repeated codeine, vadocaine and OR K-269-HCl administrations were studied. Acute administration of morphine clearly reversed the hypothermia and weight loss induced by spontaneous withdrawal from morphine. Codeine was not able to suppress the hypothermia and weight loss induced by morphine withdrawal. Acute injections of vadocaine and OR K-269-HCl did not alter these withdrawal signs either. Moreover, acute administration of codeine tended to prevent the weight loss induced by codeine withdrawal and caused behavioural changes. Spontaneous or precipitated withdrawal from repeated vadocaine or OR K-269-HCl administration caused neither hypothermia, weight loss nor behavioural changes. These results support the view that compounds vadocaine and OR K-269-HCl are free from morphine-like addictive properties.

Animals↗
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↗