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Biomedical subjects

L Ahtee

Publications and source records attributed to L Ahtee.

At least 55 records · Page 3Linked to original sources
PubMed1995

Chronic oral nicotine administration affects the circadian rhythm of dopamine and 5-hydroxytryptamine metabolism in the striata of mice.

The effect of chronic oral administration of nicotine on the circadian rhythm of striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) was studied in mice. Mice receiving nicotine in their drinking water and control mice drinking tap water were killed at 05:00, 11:00, 15:00 or 21:00 hours on the 50th day of chronic administration. The plasma concentrations of nicotine and cotinine, as well the striatal concentrations of DA, 5-HT and their metabolites 3,4 dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), homovanilic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated. The largest plasma concentrations of nicotine and cotinine were found at 05:00, when they were more than double the concentrations found at the other times studied. This indicates that the mice, typically for nocturnal animals, consumed most of their daily drinking water at night. In the control mice, the striatal DA and 3-MT concentrations showed circadian variation and were lowest at 11:00. The 5-HIAA concentrations also varied, being highest at 11:00. In the nicotine-treated mice the circadian variations in striatal monoamines were altered and more pronounced than in the controls. The concentrations of DA, DOPAC, HVA and 5-HIAA were highest at 11:00 and that of 5-HT at 21:00. The striatal DA, DOPAC, HVA and 5-HIAA concentrations in the nicotine-treated mice were significantly higher at 11:00 and the 5-HT concentrations at 21:00 than in the control mice, and, in contrast to the control mice, in the mice treated with chronic nicotine no circadian rhythm was observed in the 3-MT. No elevation of striatal DA metabolites occurred in the nicotine-treated mice compared with the controls when the plasma nicotine concentration was at its peak at 05:00. This finding suggests development of tolerance to the nicotine-induced changes in striatal DA metabolism. Further, our findings suggest that the chronic administration of nicotine in the drinking water of mice alters the circadian pattern of striatal DA and, to a lesser extent, that of 5-HT, and thus may affect the functions regulated by these transmitters.

Administration, Oral↗
PubMed1995

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen.

Rats were treated with desipramine 5 mg/kg, nomifensine 10 mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither 3[H]SCH 23390 nor 3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.

Animals↗
PubMed1995

The antiopioid peptide, neuropeptide FF, enhances the effects of acute morphine on the cerebral monoamines in rats.

The effects of neuropeptide FF (NPFF) on the changes induced by acute morphine in cerebral monoamines were studied in male Wistar rats. We measured the concentrations of noradrenaline (NA), 5-hydroxytryptamine (5-HT), dopamine and their main metabolites in the limbic area (LIM), hypothalamus (HYP) and lower brain stem (LBS). NPFF 10 micrograms x 3 at 20 min intervals, i.c.v., bilaterally) did not alter the concentrations of monoamines or their metabolites. Morphine (10 mg kg-1, s.c., 1 h) did not alter NA or 5-HT or their metabolites in any brain area studied, but elevated 3,4-dihydroxyphenylacetic acid (DOPAC) and/or homovanillic acid (HVA) in LIM and HYP. Combination of morphine and NPFF decreased NA in LIM, elevated 3-methoxy-4-hydroxyphenylethylene glycol in HYP and LBS as well as 5-hydroxyindoleacetic acid in LIM and HYP. These responses are typical to morphine at doses larger than 10 mg kg-1, and suggest a synergistic effect of the two compounds. Further, the morphine-induced elevations of DOPAC and HVA were potentiated by NPFF in LIM and HYP. In conclusion, our results suggest that NPFF does not attenuate but rather enhances the changes induced by acute morphine in the cerebral monoamines.

Animals↗
PubMed1995

Regional differences in cerebral noradrenaline turnover in mice withdrawn from repeated morphine treatment and tolerance to the effects of acute morphine.

The effects of morphine withdrawal and challenge doses (10 or 30 mg/kg) on the alpha-methyl-p-tyrosine (alpha MT)-induced noradrenaline (NA) depletion as well as on the free 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG) concentration were studied in various brain areas of NMRI mice. Morphine was given subcutaneously 3 times daily for 5 days followed by 1 or 3 days' withdrawal. In morphine withdrawn mice the alpha MT-induced NA depletion and the free MOPEG concentrations were differentially altered. At 1-day withdrawal the alpha MT-induced NA depletion was retarded and the NA concentration was elevated in the forebrain area indicating reduced release of NA. Simultaneously, however, the free MOPEG concentration was significantly elevated in the forebrain area and in the lower brain stem suggesting enhanced NA turnover. No withdrawal-induced changes were found in the hypothalamic NA turnover. Acute morphine elevated the free MOPEG concentration and accelerated the alpha MT-induced NA depletion in all brain areas of control mice but not in mice withdrawn for 1 day from repeated morphine treatment. At 3 days' withdrawal, however, the 30 mg/kg morphine dose slightly accelerated the NA depletion in the forebrain area. These results show that morphine withdrawal differentially alters the alpha MT-induced NA depletion and the free MOPEG concentration in various mouse brain areas. These effects are relatively modest suggesting that in mice the noradrenergic mechanisms play a minor role in morphine withdrawal syndrome. However, in all brain areas of the morphine-withdrawn mice tolerance was found towards the NA turnover and release accelerating effect of acute morphine.

Analysis of Variance↗
PubMed1995

Effects of selective opioid receptor antagonists on morphine-induced changes in striatal and limbic dopamine metabolism.

The effects of selective opioid receptor antagonists, beta-funaltrexamine (selective for mu receptor), naloxonazine (microliter) and naltrindole (delta) on morphine-induced changes in striatal and limbic dopamine (DA) metabolism were studied in rats. beta-Funaltrexamine (20 micrograms intracerebroventricularly) and naloxonazine (15 mg/kg intraperitoneally) were given 24 hr before morphine (15 mg/kg subcutaneously), and the rats were decapitated 60 min. after morphine. Naltrindole (1 mg/kg intraperitoneally) was given twice, 15 min. before and after morphine. Morphine significantly increased the concentrations of DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This effect was significantly antagonized by pretreatment with beta-funaltrexamine but not by naloxonazine or naltrindole. However, naloxonazine attenuated the antinociceptive effect of morphine in the hot-plate test. The concentration of DA was not significantly altered by any of the drugs studied. These results show that selective blockade of mu-opioid receptors totally blocks the increase of striatal and limbic DA metabolism induced by morphine. It seems that mu 2-subtype of mu-opioid receptor predominantly mediates this effect. Blockade of delta-opioid receptor did not alter these effects of morphine.

3,4-Dihydroxyphenylacetic Acid↗
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↗
PubMed1994

Withdrawal from repeated morphine sensitizes mice to the striatal dopamine release enhancing effect of acute morphine.

The effects of morphine withdrawal and challenge on the alpha-methyl-rho-tyrosine (alpha MT)-induced depletion of dopamine (DA) as well as on DA metabolism and 3H-SCH 23390 and 3H-spiperone binding were studied in the striata of male mice. Morphine was given s.c. 3 times daily for 5 days followed by 1 to 3 days' withdrawal. The alpha MT-induced DA depletion was retarded in mice withdrawn for 1 day from repeated morphine. At this time point the striatal concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) fell, too. In mice withdrawn for 3 days from morphine neither DA depletion nor DOPAC or HVA concentrations differed from those of control mice. In control mice acute morphine challenge accelerated the DA depletion at the dose 10 mg/kg but not at the dose 30 mg/kg. Both doses elevated striatal DOPAC and HVA. In mice withdrawn from repeated morphine for 1 day acute morphine partially counteracted the withdrawal-induced retardation of DA depletion and elevated striatal DOPAC and HVA clearly less than in control mice. However, in mice withdrawn for 3 days 10 mg/kg of morphine clearly enhanced DA depletion and its effect on striatal HVA was significantly augmented. In these mice as in controls the 30 mg/kg dose did not alter striatal DA depletion and elevated HVA less than in controls. Acute morphine did not alter striatal 3-methoxytyramine (3-MT) concentration in control mice but at the dose 10 mg/kg increased it in mice withdrawn for 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Role of dopamine receptors in the dual effect of naloxone on quinpirole-induced yawning in morphine pretreated rats.

The present study was undertaken to determine the state of sensitivity of dopamine D2/D3 receptors involved in the mediation of yawning behaviour at various times following acute morphine administration to rats. Morphine (3.0 mg/kg, s.c.) induced a biphasic effect on locomotor activity: an initial inhibitory phase lasting for about 30 min was after about an hour followed by a phase of locomotor activation lasting for about 60 min. Dopamine D2/D3 receptor agonist quinpirole (0.01-0.1 mg/kg, s.c.) induced yawning behaviour in rats. Morphine given at 15 or 60 min before (inhibitory phase) inhibited the yawning response to quinpirole (0.1 mg/kg) but not when given at 90 or 120 min before (stimulatory phase). Naloxone (1.0 mg/kg) given 10 min before quinpirole restored yawning inhibited by morphine pretreatment during the inhibitory phase (15-60 min after morphine). However, during the morphine-induced stimulatory phase naloxone strongly inhibited the yawning response to quinpirole. D1 receptor antagonist SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol hemimaleate] at 0.01 mg/kg did not affect quinpirole-induced yawning or its inhibition by morphine. However, in rats which received morphine 90 min prior to testing yawning, SCH 23390 enhanced quinpirole-induced yawning behaviour as compared with morphine- or saline-pretreated animals. The data obtained in the present study indicate that morphine pretreatment initially induces a lack of responsiveness of the D2/D3 receptors mediating yawning behaviour and subsequently increases their sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Concurrent nimodipine attenuates the withdrawal signs and the increase of cerebral dihydropyridine binding after chronic morphine treatment in rats.

The effect of chronic administration of dihydropyridine calcium channel antagonist nimodipine (1 mg/kg/day) given concurrently with morphine on the signs of morphine withdrawal and on the [3H]nitrendipine binding in the rat brain has been investigated. Chronic morphine administration in increasing daily doses from 20 mg/kg to 70 mg/kg for 24 days and consequent withdrawal for 24 h induced loss of body weight, wet dog shakes, episodes of writhing and yawning behaviour. The density of [3H]nitrendipine binding was elevated in the cortex and limbic structures but not in the striatum after chronic morphine treatment. Chronic concurrent administration of nimodipine prevented the loss of body weight and reduced the scores of wet dog shakes and writhing, but did not affect yawning behaviour at 24 h after morphine withdrawal. The concurrent nimodipine treatment also prevented the rise in the density of central dihydropyridine binding sites which occurred upon chronic morphine treatment. These results suggest that chronic nimodipine treatment attenuates the development of the withdrawal signs which occur upon the termination of chronic morphine treatment by preventing the up-regulation of the central dihydropyridine-sensitive binding sites.

Animals↗
PubMed1993

Effects of intraventricular taurine, homotaurine and GABA on serum prolactin and thyrotropin levels in female and in male rats.

Serum prolactin and thyrotropin levels of conscious, unrestrained male and female rats were compared after intracerebroventricular (i.c.v.) administration of taurine, gamma-aminobutyric acid (GABA) and homotaurine. The amino acids studied had no clear effect on serum basal thyrotropin levels in male or female rats. All amino acids elevated serum prolactin levels in female rats at the dose of 5 mumol/rat; homotaurine by about 18-fold, taurine and GABA by 3-fold. Only homotaurine elevated serum prolactin of male rats at this dose, but its effect was less pronounced (p < 0.01) in male than in female rats. Although homotaurine was clearly more potent than the two other amino acids, at the dose of 10 mumol/rat taurine and GABA also elevated serum prolactin in male rats. These findings show that there are gender-related differences in the responses of serum prolactin levels to homotaurine, taurine and GABA in rats. The tuberoinfundibular dopaminergic pathway, which exerts tonic inhibitory influence on prolactin secretion, is sexually differentiated. Hence the gender-related differences in the effects of the amino acids on prolactin secretion suggest that they might inhibit dopamine release from the median eminence. In case of homotaurine, the gender effect was most pronounced. The less clear dependence of GABA's effect on the gender is in accordance with the suggestions that GABA influences the secretion of serum prolactin by more than one mechanism.

Animals↗
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↗