Search PubMed⌕ Search

Biomedical subjects

L Ahtee

Publications and source records attributed to L Ahtee.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of morphine on metabolism of dopamine and serotonin in brains of alcohol-preferring AA and alcohol-avoiding ANA rats.

Morphine induces a larger locomotor stimulation in the alcohol-preferring AA rats than in the alcohol-avoiding ANA rats. We have now studied the acute effects of morphine (1 and 3 mg/kg) on metabolism of dopamine and serotonin (5-HT) in the dorsal and ventral striatum of the AA and ANA rats. The basal level of dopamine release, as reflected by the concentration of dopamine metabolite 3-methoxytyramine (3-MT), was lower in the caudate-putamen and nucleus accumbens of the AA rats than in the ANA rats. In the caudate-putamen, morphine increased dopamine metabolism and release more in the AA than in the ANA rats. In the nucleus accumbens and olfactory tubercle, the effects of morphine on dopamine metabolism and release did not differ between the rat lines. Morphine elevated the metabolism of 5-HT in the caudate-putamen and nucleus accumbens of the AA but not in those of the ANA rats. The results suggest that the larger morphine-induced psychomotor stimulation of the AA rats in comparison with the ANA rats is associated with the larger effect of morphine on dopamine metabolism in the caudate-putamen and 5-HT metabolism in the caudate-putamen and nucleus accumbens. Furthermore, low basal dopamine release may play a role in the high alcohol-preference of AA rats.

Alcohol Drinking↗
PubMed1999

The involvement of noradrenergic transmission in the morphine-induced locomotor hyperactivity in mice withdrawn from repeated morphine treatment.

1. Our previous studies suggest that in addition to the cerebral dopaminergic systems the noradrenergic ones have a crucial role in the morphine-induced behavioural sensitization in mice. Therefore the effects of alpha2-adrenoceptor antagonist, idazoxan (1 and 3 mg kg(-1), i.p.) on morphine-induced locomotor hyperactivity as well as on morphine-induced changes in cerebral noradrenaline (NA) and striatal dopamine (DA) metabolism were studied in mice withdrawn for 3 days from 5 day repeated morphine treatment. The concentrations of NA, free 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 3-methoxytyramine (3-MT) were determined. 2. Acute morphine (10 mg kg(-1), s.c.) increased locomotor activity in control and in morphine-withdrawn mice; idazoxan alone did not alter the activity. Idazoxan pretreatment did not alter the locomotor hyperactivity induced by acute morphine in control mice but potentiated it in morphine-withdrawn mice. 3. Acute morphine elevated MOPEG less but increased DOPAC and HVA more clearly in morphine-withdrawn mice than in controls, and decreased 3-MT only in controls. Idazoxan alone did not alter the NA or DA metabolite concentrations in control mice, but elevated MOPEG as well as DOPAC in morphine-withdrawn mice. 4. In control mice idazoxan enhanced acute morphine's elevating effect on MOPEG. In withdrawn mice idazoxan counteracted the tolerance so that acute morphine elevated MOPEG in these mice to about similar level as in controls. 5. Idazoxan pretreatment abolished the HVA increasing effect of acute morphine both in control and withdrawn mice. In control mice idazoxan enhanced morphine's elevating effect on DOPAC and abolished morphine's decreasing effect on 3-MT. Idazoxan did not alter morphine's effects on DOPAC or 3-MT concentrations in withdrawn mice. 6. Our results show that in morphine-withdrawn mice idazoxan pretreatment reveals the morphine-induced locomotor sensitization. This most probably occurs by overcoming the tolerance towards the acute morphine-induced increase of cerebral NA turnover and release. It is suggested that in mice the cerebral noradrenergic in addition to the dopaminergic systems are major determinants of the behavioural sensitization to morphine.

Animals↗
PubMed1999

Characterization of the decrease of extracellular striatal dopamine induced by intrastriatal morphine administration.

The effect of intrastriatally-administered morphine on striatal dopamine (DA) release was studied in freely moving rats. Morphine (1, 10 or 100 microM) was given into the striatum by reversed microdialysis, and concentrations of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were simultaneously measured from the striatal dialysates. Intrastriatally-administered morphine significantly and dose-dependently decreased the extracellular concentration of DA, the concentrations of the acidic DA metabolites were only slightly decreased. The effect of morphine was antagonized by naltrexone (2.25 mg kg(-1), s.c.). Pretreatment with a preferential kappa-opioid receptor antagonist, MR2266 [(-)-5,9 alpha-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphane; 1 mg kg(-1), s.c.], had no effect on the decrease of extracellular DA evoked by intrastriatal morphine (100 microM). Intrastriatal administration of the selective micro-opioid receptor agonist [D-Ala2,MePhe4,Gly-ol5] enkephalin (DAMGO; 1 microM), significantly decreased the extracellular concentration of DA in the striatum. When the rats were given morphine repeatedly in increasing doses (10-25 mg kg(-1), s.c.) twice daily for 7 days and withdrawn for 48 h, the decrease of extracellular DA induced by morphine (100 microM) was significantly less than that seen in saline-treated controls. Our results show that besides the well-known stimulatory effect there is a local inhibitory component in the action of morphine on striatal DA release in the terminal regions of nigrostriatal DA neurones. Tolerance develops to this inhibitory effect during repeated morphine treatment. Furthermore, our results suggest that the effect of intrastriatally-administered morphine is mediated by the micro-opioid receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Locally infused taurine, GABA and homotaurine alter differently the striatal extracellular concentrations of dopamine and its metabolites in rats.

We studied in vivo the effects of locally infused taurine (50, 150, and 450 mM) on the striatal dopamine and its metabolites in comparison with those of GABA and homotaurine, a GABAA receptor agonist, in freely moving rats. The extracellular dopamine concentration was elevated maximally 2.5-, 2- and 4-fold by taurine, GABA and homotaurine, respectively. At 150 mM concentration, at which the maximum effects occurred, homotaurine increased the extracellular dopamine more than taurine or GABA. When taurine and GABA were infused simultaneously with tetrodotoxin the output of dopamine did not differ from that in the presence of tetrodotoxin alone. In comparison, tetrodotoxin did not inhibit the increase in extracellular dopamine caused by homotaurine. Furthermore, omission of calcium from the perfusion fluid inhibited the increase of extracellular dopamine caused by GABA. However, it did not block the increase of dopamine caused by taurine or homotaurine. The present study suggests that the effects of intrastriatal taurine, GABA and homotaurine on the striatal extracellular dopamine differ. Thus, these amino acids seem to affect the striatal dopaminergic neurons via more than one mechanism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Regulation of nicotinic receptors in the brain of mice withdrawn from chronic oral nicotine treatment.

The effect of nicotine withdrawal on regional regulation of brain nicotinic receptors was studied in mice after chronic administration of nicotine in the drinking water for 2, 4 or 7 weeks. Two weeks of chronic nicotine administration did not alter the binding of [3H]-nicotine in the midbrain, cortex or cerebellum of the mice, while after both 4-and 7-week treatments a significant increase in the specific [3H]-nicotine binding was observed in cortical and midbrain membranes. In the midbrain, the [3H]-nicotine binding was increased by about 40% in mice withdrawn for 48-72 h from the 4-week chronic nicotine treatment and in mice withdrawn for 48 h from the 7-week treatment. The [3H]-nicotine binding was significantly increased (by 55-65%) in the cortex at 48 h and 72 h after withdrawal from 4-week chronic nicotine and it was even somewhat more increased (by 72-66%) after 7-week treatment. The cortical [3H]-nicotine binding was not altered at 24 h after the 4-week treatment, but in mice withdrawn for 24 h from the 7-week treatment it was increased by 116%. The increases in [3H]-nicotine binding returned to control levels within 1 week after withdrawal. None of the studied treatments affected the [3H]-nicotine binding in the cerebellum. Tolerance towards nicotine-induced locomotor depression was only found in mice withdrawn for 24 h from the 7-week chronic nicotine administration. These findings suggest that at least 4-week chronic nicotine administration in the drinking water is needed before any upregulation of nicotinic receptors can be observed. Furthermore, in our experiments the increase in the [3H]-nicotine binding was seen before behavioural tolerance could be demonstrated. The differences between brain regions in the time course of nicotinic receptor upregulation may reflect variations in nicotinic receptor subunits and their sensitivity to chronic nicotine treatment.

Administration, Oral↗
PubMed1998

Conditioned place preference induced by a combination of L-dopa and a COMT inhibitor, entacapone, in rats.

The interaction of dopamine (DA) precursor L-dopa and catechol-O-methyltransferase (COMT) inhibitor, entacapone, was examined in rats using conditioned place preference (CPP) paradigm to assess reinforcement, and by measuring DA metabolism in the striatum and the limbic forebrain. Neither L-dopa (100 mg/kg i.p.) nor entacapone (30 mg/kg i.p.) alone induced CPP, but in combination they induced significant CPP. Entacapone alone had no effect on limbic or striatal DA concentrations, while it reduced the concentrations of the COMT products 3-methoxytyramine (3-MT), a metabolite reflecting DA release, and homovanillic acid (HVA) in both brain areas. L-dopa elevated limbic but not striatal 3-MT. L-dopa also slightly elevated limbic DA but had no effect on striatal DA concentration. L-Dopa-induced increase of 3-MT was attenuated by entacapone. Our results show for the first time that L-dopa is able to produce CPP in intact animals. This effect may be related to the findings that L-dopa increases synaptic DA concentrations in the limbic areas, and entacapone may enhance this elevation as it prevents the synaptic metabolism of DA.

Animals↗
PubMed1997

Voluntary alcohol drinking selectively accelerates dopamine release in the ventral striatum as reflected by 3-methoxytyramine levels.

Alcohol-preferring Alko, Alcohol (AA) rats with free access to food and water were taught to voluntarily consume 10% alcohol solution during 20-min sessions. After the drinking session, rats had elevated dopamine release (as reflected by 3-methoxytyramine concentrations) in the nucleus accumbens, olfactory tubercle, and caudate-putamen. When alcohol solution was replaced by plain water, dopamine release was increased only in the caudate-putamen, indicating selective activation of the mesolimbic dopaminergic pathway by alcohol.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Involvement of opioid mu 1 receptors in morphine-induced conditioned place preference in rats.

The main purpose of this study was to evaluate the role of mu 1-opioid receptors in morphine reward. Therefore, we studied the ability of a mu 1-selective antagonist, naloxonazine [15 mg/kg intraperitoneally (IP)], to antagonize the conditioned place preference (CPP) induced by morphine [3 mg/kg subcutaneously (SC)]. In addition, effects of naloxonazine on morphine-induced catalepsy (15 mg/kg), analgesia (3 mg/kg), and hyperthermia (3 mg/kg) were studied. For comparison, the effects of a nonselective opioid receptor antagonist, naltrexone (2.5 mg/kg SC), and a selective delta-opioid receptor antagonist, naltrindole (2 mg/kg IP), on CPP induced by morphine were investigated. Morphine-induced CPP was clearly antagonized by pretreatment with naloxonazine and naltrexone (12 h and 20 min prior to morphine, respectively) but not by naltrindole (15 min before morphine). Naloxonazine also antagonized morphine-induced catalepsy and analgesia but not morphine-induced hyperthermia. Naltrindole did not modify morphine-induced catalepsy. These results suggest an active role for mu 1-opioid receptors in morphine reward, whereas morphine-induced hyperthermia does not appear to be mediated by mu 1-opioid receptors. Furthermore, delta-opioid receptors seem to be without significance in morphine-induced reward.

Analgesics, Opioid↗
PubMed1997

Role of cerebral dopamine and noradrenaline in the morphine-induced locomotor sensitisation in mice.

The effects of morphine on locomotor activity and cerebral dopamine (DA) and noradrenaline (NA) metabolism were studied in mice treated repeatedly with morphine for 5 days followed by 1, 3, or 5 days of withdrawal. Acute morphine treatment did not increase the locomotor activity of mice withdrawn for 1 day, after withdrawal for 3 days the increase was similar to that in controls, and after 5 days the increase was clearly larger than in controls. In mice withdrawn for 3 or 5 days, but not in control mice, acute morphine significantly elevated striatal 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations. Acute morphine challenge decreased striatal 3-methoxytyramine in control mice, but did not alter it in mice withdrawn for 3 or 5 days. In mice withdrawn for 3 days acute morphine increased the free 3-methoxy-4-hydroxyphenylethylene glycol in all brain areas studied clearly less than in controls, whereas in mice withdrawn for 5 days the tolerance was found only in the hypothalamus. Our results show that the morphine-induced locomotor hyperactivity is enhanced in mice after sufficiently long withdrawal, when mice are sensitised to the acute morphine-induced increase of DA turnover but the tolerance to morphine's effects on cerebral NA is disappearing, suggesting that in mice the cerebral NAergic systems, in addition to the DAergic ones, are major determinants of the behavioural response to morphine.

Animals↗
PubMed1996

Tolerance to nicotine's effects on striatal dopamine metabolism in nicotine-withdrawn mice.

After 7-week chronic administration of nicotine to mice in their drinking water, nicotine was withdrawn for 24 h. Acute nicotine challenge (1 mg/kg s.c., 60 min) elevated the striatal concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and decreased the concentration of 3-methoxytyramine significantly less in the mice withdrawn for 24 h from nicotine than in the control mice which had been drinking tap water under identical conditions for 7 weeks. Neither withdrawal nor the acute nicotine challenge altered the striatal dopamine concentration. No alterations were found in the density or affinity of the specific binding of [3H]SCH 23390 or [3H]spiperone to striatal membrane homogenates during nicotine treatment or after its withdrawal. Thus, our results show that tolerance to the acute effects of nicotine on striatal dopamine metabolism can be induced by administering nicotine to mice in the drinking water. However, neither chronic nicotine treatment nor its withdrawal seem to affect dopamine D1 and D2 receptors in the striatum.

Animals↗
PubMed1996

Intrastriatal taurine increases striatal extracellular dopamine in a tetrodotoxin-sensitive manner in rats.

In vivo effects of locally administered taurine on striatal dopamine release and metabolism were studied by microdialysis in freely moving rats. Concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in striatal dialysates were quantified by high pressure liquid chromatography (HPLC) using electrochemical detection. Infusion of 150 mM taurine into the striatum for 2 h induced a 2.5-fold increase in the extracellular dopamine concentration. Extracellular DOPAC concentration increased nearly 2-fold. Taurine infusion initially decreased HVA to 70% but afterwards increased it to 140% of the control. When taurine was infused simultaneously with 1 microM tetrodotoxin starting 60 min after tetrodotoxin, the output of dopamine did not differ from that in the presence of tetrodotoxin alone. Tetrodotoxin abolished the effects of taurine on dopamine metabolites as well. Tetrodotoxin-sensitivity of the effects of taurine on dopamine and its metabolites suggests that intrastriatal taurine elevates extracellular dopamine by releasing it from neuronal pool.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Taurine infused intrastriatally elevates, but intranigrally decreases striatal extracellular dopamine concentration in anaesthetised rats.

In the present study we infused taurine (50, 150 or 450 mM, 2 microliters/min for 4h) into the dorsal striatum or into the substantia nigra via microdialysis probe and estimated the extracellular concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the dorsal striatum of anaesthetised rats. Intrastriatal infusion of taurine elevated striatal dopamine at all concentrations studied. At the 450 mM concentration taurine elevated the extracellular dopamine 10-fold, but only in the first 30 min sample after starting the taurine infusion. At 50 and 150 mM taurine elevated dopamine throughout the 4h infusion maximally up to 3-4-fold the control level. Extracellular DOPAC was increased by 150 and 450 mM taurine (up to about 150-160% of the control level), whereas at all three concentrations taurine decreased HVA to about 85% of the control; however, the decrease caused by 450 mM taurine was short-lasting. At all three concentrations taurine infused into the substantia nigra decreased the extracellular dopamine in the ipsilateral striatum to about 40-50% of the control, and increased extracellular DOPAC and HVA maximally to about 150% and 170% of the control, respectively. These results show that the effects of taurine on the concentrations of extracellular dopamine and its metabolites depend on its administration site on nigrostriatal dopaminergic neurons. It elevates the extracellular dopamine when given into the striatum, but when given into the cell body region of the nigrostriatal dopaminergic pathway it decreases the extracellular dopamine in the ipsilateral striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Morphine- and cocaine-induced conditioned place preference: effects of quinpirole and preclamol.

The role of dopamine in opioid reward is unresolved. Furthermore, the issue is somewhat unclear regarding cocaine and the place preference paradigm. In the present study we investigated whether the drugs activating dopamine autoreceptors affect cocaine- and morphine-induced place preference in rats. Neither the dopamine D2/D3 receptor agonist, quinpirole (0.05 mg/kg, SC), nor the partial dopamine autoreceptor agonist, preclamol (2 or 8 mg/kg, SC), induced place conditioning by itself. Quinpirole had no significant influence on the place preference induced either by morphine (3 mg/kg, SC) or cocaine (5 mg/kg, IP). Preclamol, when given at the dose of 8 mg/kg SC, significantly attenuated the effect of cocaine but failed to modify the effect of morphine. Our results suggest that the rewarding properties of morphine involve DA-independent mechanisms whereas in the cocaine-induced reward the role of brain DA is critical. Furthermore, as regards place conditioning, we propose that the activation of DA autoreceptors is not sufficient to reliably modify the rewarding effect of cocaine.

Animals↗
PubMed1996

Expression of Fos protein in various rat brain areas following acute nicotine and diazepam.

We studied the effects of an acute dose of (-)-nicotine (1 mg/kg) on Fos-like immunostaining (IS) in rat brain areas. Nicotine increased Fos IS significantly in the medial terminal nucleus of accessory optic tract (MT), and tended to increase it in the interpeduncular nucleus (i.p.), as well as in the stress-related areas, the paraventricular hypothalamic nucleus (PVN) and the supraoptic nucleus (SON). Previously nicotine was reported to increase Fos IS also in another stress-related area, the central nucleus of amygdala (ACe). This led us to study the interaction of nicotine with diazepam (10 mg/kg). Diazepam alone increased Fos IS in PVN and in SON as well as in ACe. In diazepam- and nicotine-treated rats Fos IS was increased in PVN and SON as well as in MT and i.p.. In MT and i.p. of diazepam and nicotine-treated rats Fos IS was similar to that induced by nicotine alone, and in PVN and SON of these rats Fos IS in ACe. Taken together, diazepam induced Fos IS in all stress-related areas studied (PVN, SON, ACe), but not in central visual structures, where nicotine induces Fos IS (MT, i.p.). No significant interactions on Fos expression were found between acute effects of diazepam and nicotine suggesting that these drugs activate different sets of neurons within the stress-related brain areas.

Amino Acid Sequence↗
PubMed1996

Behavioural and neurochemical sensitization of morphine-withdrawn rats to quinpirole.

The sensitivity of dopamine D2-like receptors in morphine-withdrawn rats was studied using the selective agonist quinpirole. Morphine was administered twice daily increasing the daily dose from 20 to 50 mg/kg during 7 days. Twenty-four hours after the last morphine administration the rats were given quinpirole (0.01-1 mg/kg) and their behavior was assessed. Withdrawal from repeated morphine treatment enhanced yawning behavior and penile erections induced by small doses (0.01-0.1 mg/kg) as well as the intensity of stereotypy induced by a large dose (1.0 mg/kg) of quinpirole. In the morphine-withdrawn rats the dose of 1 mg/kg of quinpirole caused less yawning than in the control rats, whereas the number of erections induced by this dose was enhanced as compared with the control animals. In the control rats, the striatal and limbic concentrations of dopamine metabolites, 3,4-dihydroxphenylacetic acid (DOPAC), and homovanillic acid (HVA), were not clearly affected by the smallest dose of quinpirole. However, the small dose of quinpirole (0.01 mg/kg) significantly reduced the levels of DOPAC and HVA in the striatum and limbic forebrain of the rats withdrawn from morphine either for 24 or 48 h. These findings indicate that withdrawal from repeated morphine treatment enhances the sensitivity of dopamine D2-like receptors.

Animals↗
PubMed1996

5-HT3 receptor antagonist MDL 72222 dose-dependently attenuates cocaine- and amphetamine-induced elevations of extracellular dopamine in the nucleus accumbens and the dorsal striatum.

The effects of a 5-HT3 receptor antagonist MDL 72222 on cocaine- and amphetamine-induced increases in extracellular dopamine in the nucleus accumbens and the dorsal striatum were studied with microdialysis technique using halothane anaesthesized rats. Dopamine and its metabolites were measured by HPLC with electrochemical detection. Cocaine elevated extracellular dopamine in the nucleus accumbens and to a lesser extent in the dorsal striatum, but it did not affect dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid. Pretreatment with MDL 72222 (25-100 micrograms/kg) dose-dependently attenuated cocaine-induced elevation of dopamine in both of the nuclei studied. Amphetamine elevated extracellular dopamine and reduced DOPAC and homovanillic acid equally in the nucleus accumbens and in the dorsal striatum. MDL 72222 also attenuated the amphetamine-induced elevation of extracellular dopamine concentration in both brain areas studied, but first at a dose of 100 micrograms/kg. The different potencies of the interactions of the 5-HT3 receptor antagonist with cocaine and amphetamine could be related to the different mechanisms by which these drugs primarily elevate extracellular dopamine.

Amphetamine↗
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↗