Biomedical subjects

M M Airaksinen

Publications and source records attributed to M M Airaksinen.

At least 19 recordsLinked to original sources

PubMed2000

Ligand interaction with the purified serotonin transporter in solution and at the air/water interface.

The purified serotonin transporter (SERT) was spread at the air/water interface and the effects both of its surface density and of the temperature on its interfacial behavior were studied. The recorded isotherms evidenced the existence of a stable monolayer undergoing a lengthy rearrangement. SERT/ligand interactions appeared to be dependent on the nature of the studied molecules. Whereas an unrelated drug (chlorcyclizine) did not bind to the spread SERT, it interacted with its specific ligands. Compared to heterocyclic drugs, for which binding appeared to be concentration-dependent, a 'two-site' mechanism was evidenced for pinoline and imipramine.

Air↗

PubMed1998

The fasciculus retroflexus controls the integrity of REM sleep by supporting the generation of hippocampal theta rhythm and rapid eye movements in rats.

The fasciculus retroflexus (FR) fiber bundle comprises the intense cholinergic projection from the medial division of the habenula nucleus (Hbn) of the epithalamus to the interpeduncular nucleus (IPN) of the limbic midbrain. Due to the widespread connections of the Hbn and IPN, it could be surmised that the FR is integrated in the processings of various subsystems that are known to be involved in the sleep-wake mechanisms; relevant sites include the limbic forebrain and midbrain areas and more caudal pontine structures. Consequently, the present study addressed the significance of the FR in the spontaneous sleep-wake stage-associated variations of the different activity patterns of frontal cortex and hippocampal electroencephalograms (EEGs), the electrooculogram, and body movements, in freely behaving rats that had been subjected to either bilateral electrolytic lesioning of the FR or control operations. The evolution of different state combinations was assessed by the combinatory analysis of different activity stages appearing on the 6-h records. As compared to the control-operated group, the FR lesioning substantially reduced the time spent in rapid eye movement (REM) sleep by 79%, moderately decreased the duration of the intermediate state of sleep by 29%, and quiet waking state by 44%, but had virtually no effects on the durations of different types of non-REM sleep (i.e., drowsiness that which involved quiet sleep or slow-wave sleep containing delta and spindle state components) or on the times of active waking behavior that corresponded to the body movements. Quantitative decomposition analyses revealed marked variations in the frontal cortex and hippocampal activity as well as REM during the course of the extracted sleep-wake stages described and there were also some group differences. Of those individual features that were used to determine different sleep-wake stages, the overall hippocampal theta time (41% decrease) and single REM frequency (71% reduction during the REM sleep) were most affected. In contrast, the various properties of desynchronization/synchronization patterns of frontal cortex EEGs were consistently hardly influenced by the FR lesioning. Therefore, the present data suggest the involvement of the FR in the REM sleep processes by establishing prominent associations with the limbic and REM control mechanisms that involve the hippocampus and plausibly pontine ocular activity networks.

Animals↗

PubMed1997

Binding of pinoline on the 5-hydroxytryptamine transporter: competitive interaction with [3H] citalopram.

Pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline) is a naturally occurring compound in the mammalian body which inhibits 5-hydroxytryptamine (5-HT) uptake and exerts antidepressant-like behavioural effects in rats. The present study investigates the effects of pinoline on [3H]citalopram binding to the 5-HT transporter on rat brain. Our experiments revealed that pinoline inhibits [3H]citalopram binding with IC50 1255 +/- 167 nM and Ki 572 +/- 76 nM; Hill coefficient for inhibition was close to 1. In saturation experiments, pinoline co-incubated with [3H]citalopram, increased dose-dependently the Kd value but had no effect on the Bmax value of [3H]citalopram binding. Micromolar concentrations of pinoline did not have influence on the dissociation rate of specifically bound [3H]citalopram. Binding parameters of [3H]citalopram did not differ significantly in cerebral cortex and hippocampus of rats treated for 10 days with pinoline or vehicle. These results indicate that pinoline did not have any modulative influence on the activity of 5-HT transporter and it interacts competitively with citalopram on the substrate recognition site of the 5-HT transporter.

Animals↗

PubMed1996

Histaminergic modulation of neocortical spindling and slow-wave activity in freely behaving rats.

Histaminergic H3 receptor antagonists stimulate neuronal histamine release and could consequently have a number of physiological effects in the brain. The effects of H3 receptor blockade, induced by systemically administered thioperamide, were assessed on the frontal cortex electroencephalographic (EEG) properties in freely behaving rats. The relationship of EEG activity variables to endogenous brain histaminergic markers was also examined, both in controls and in portocaval anastomosis (PCA)-operated rats (which show increased levels of brain histamine and t-methylhistamine). Thioperamide reduced the incidence of thalamus-regulated EEG spindles, while it slightly increased their amplitude. It furthermore reduced the spectral power of low-frequency (1.5-5Hz) EEG, which effect was equally distributed over the spindle and non-spindle EEG states. These EEG effects were accompanied by increased motor activity of the animals. Both the low-frequency EEG activity and spindle incidence correlated inversely with the histamine level of the brain (hypothalamus and cerebellum excluded) while t-methylhistamine level correlated with the degree of thioperamide-induced reduction of slow-wave EEG activity. The present results provide evidence for the involvement of endogenous brain histamine level, histamine release (as assessed by t-methylhistamine level) and H3 receptors in the histaminergic regulation of neocortical synchronization patterns assumed to be linked to arousal control.

Animals↗

PubMed1996

Formation of tetrahydroharman (1-methyl-1,2,3,4-tetrahydro-beta-carboline) by Helicobacter pylori in the presence of ethanol and tryptamine.

Helicobacter pylori contains alcohol dehydrogenase which oxidizes ethanol to acetaldehyde. In the present study, H. pylori cytosol was incubated in a buffered media at pH 6.0 and 7.4 in the presence of ethanol and tryptamine. Under these conditions, tetrahydroharman (1-methyl-tetrahydro-beta-carboline) was produced as a condensation product of tryptamine and acetaldehyde. At pH 6.0, 20.60 +/- 5.00% of the added tryptamine was converted to tetrahydroharman, while 27.00 +/- 4.80% (mean +/-SD) was converted at pH 7.4. Similar reactions between acetaldehyde and other dietary amines seem likely. Such biogenic alkaloids, if formed in vivo, might contribute to the dysphoric effects of alcohol.

Acetaldehyde↗

PubMed1994

Differential regulation of cyclic GMP levels in the frontal cortex and the cerebellum of anesthetized rats by nitric oxide: an in vivo microdialysis study.

A microdialysis method combined with a sensitive radioimmunoassay was used to monitor extracellular cyclic GMP (cGMP) levels in the frontal cortex and the cerebellum of anesthetized rats in vivo. Basal cGMP release remained constant throughout the perfusion period and was approximately 2 fmol/30 min in the frontal cortex and approximately 4 fmol/30 min in the cerebellum. The nitric oxide (NO) donor sodium nitroprusside (SNP) stimulated cGMP release transiently in both regions. However, the maximal response was 3-fold in the frontal cortex (obtained with 5 microM SNP) but 90-fold in the cerebellum (obtained with 1 mM SNP). Perfusion with the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) suppressed cerebellar cGMP release by 74% indicating that NO is the major regulator of basal cGMP levels in the cerebellum. Quite opposite, L-NAME exhibited no potency in the frontal cortex suggesting that other activators of guanylyl cyclase may regulate basal cortical cGMP levels in vivo.

Animals↗

PubMed1994

Platelet serotonin uptake sites increased in drinkers of ayahuasca.

The binding of [3H]citalopram to the platelet 5-hydroxytryptamine (5-HT) transporter was measured in a group of healthy male drinkers of ayahuasca, a psychoactive sacrament indigenous to Amazonia, and a group healthy male controls. An increased number of binding sites (Bmax) in the platelets of ayahuasca drinkers was found, while the dissociation constant (Kd) remained the same for both groups. If indicative of neuronal 5-HT uptake activity, these results would suggest a decreased concentration of extracellular 5-HT, or a response to increased production and release of 5-HT. Such changes in 5-HT synaptic activity, in this case, should not be misinterpreted as an indication of developing neurological or psychiatric illness.

Adult↗

PubMed1994

Influence of flumazenil on the learning-enhancing effect of ambocarb in rats.

The effects of flumazenil (Ro 15-1788) and a new beta-carboline, ambocarb (AMB), on learning were investigated using the multichoice maze. The drugs, administered either alone or simultaneously, were injected once a day before training for eight days. AMB, administered alone, improved the performance and decreased the working errors, whilst flumazenil had no effect on performance during its sole administration but weakly prevented the learning-improving effect of AMB. More significantly, flumazenil antagonized the motor activity depressed by AMB. In the study ex vivo, flumazenil decreased and AMB increased the apparent affinity of [3H]flunitrazepam to the central benzodiazepine receptors. Flumazenil reversed the action of AMB on the central benzodiazepine receptors, but failed to reduce significantly the modulative effects of AMB on [3H]muscimol and [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding. These data indicate that flumazenil, due to its action on the central benzodiazepine receptors, more effectively reverses the inhibition of motor activity than the performance-improving effect of AMB.

Animals↗

PubMed1994

Inhibition of brain histamine synthesis increases food intake and attenuates vasopressin response to salt loading in rats.

Alpha-fluoromethylhistidine (FMH), a histamine synthesis inhibitor, was infused into the lateral cerebral ventricle of male Long-Evans rats for 7 days at a dose of 60 mcg/day. During this period animals were housed in metabolic cages; water and food consumption were measured and urine samples were collected. FMH-treated rats ate significantly more than controls and had a significantly greater weight increase. Concomitantly, sodium and potassium excretion increased. On the seventh day, rats were injected i.p. with 6.67 ml/kg of either 5.8% NaCl or physiological saline. Animals were decapitated 1 h after injection and plasma vasopressin, corticosterone and posterior pituitary vasopressin levels were determined by radioimmunoassay. NaCl loading significantly increased plasma vasopressin in control rats but not in rats pretreated with FMH. FMH alone had no effect. There were no significant changes in pituitary vasopressin or plasma corticosterone. These results clearly suggest an inhibitory role for the histaminergic system in the regulation of food intake. They also agree with, although not proving, the stimulatory control of vasopressin release by the histaminergic system in rat brain.

Animals↗

PubMed1992

Fast cyclic voltammetry of oxidizable species; depth profile in the rat striatum with and without potassium stimulation of the median forebrain bundle.

Fast cyclic voltammetry was used to monitor the release of dopamine in the caudate nucleus following potassium stimulation of the median forebrain bundle and to determine the characteristics of the small basal oxidation current while dipping of an electrode with a large tip (0.3 mm) in the caudate nucleus. The oxidation current was shown to be greater just after the electrode reached the caudate area than at a time 15-20 s after its arrival. There was less current increase observed when the tip reached the cortex and no current was observed in the white matter or with the electrode returning or with repeated passage along the same track. Potassium stimulation of median forebrain bundle induced an initial low magnitude dopamine release which disappeared within minutes. The basal oxidation current increased step by step after a few potassium stimulations. This effect was not blocked by pargyline (75 mg/kg) whereas L-DOPA (200 mg/kg) was shown to increase it. It is thought that the large tip of the lowered electrode can destroy neurons and induce the release of intracellularly stored compounds into the extracellular space. We consider also dopamine to be responsible for the increase in oxidizable current just after the electrode movement stopped.

Animals↗

PubMed1992

The effect of chronic treatment with peripheral benzodiazepine receptor ligands on behavior and GABAA/benzodiazepine receptors in rat.

Rats were twice daily (2 x 10 mg/kg, i.p.) treated for three weeks with the peripheral benzodiazepine (BZ) receptor ligands Ro 5-4864 (4'-chlorodiazepam) and PK 11,195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carbox ami de). After the first injection there were no differences between the drug-treated and control animals in behavioral tests. After 10 days treatment, the number of sniffings was increased in Ro 5-4864-treated rats. After the last injection, sniffings and ambulations were decreased in PK 11,195-treated animals. The number of rearings and groomings remained unchanged throughout the treatment, and there were no changes in the results in the elevated plus-maze test. Apparently these compounds are devoid of anxiolytic and anxiogenic effects at moderate doses. The effect of 72 a h withdrawal from the above mentioned chronic treatment on peripheral and central BZ receptors as well as on GABAA receptors was studied with receptor binding techniques using 3H-Ro 5-4864, 3H-flumazenil and 3H-muscimol, respectively, as ligands. The number of GABAA and central BZ receptors was lower after Ro 5-4864 treatment, as was the effect of progesterone-induced stimulation of 3H-muscimol binding. The number of peripheral BZ receptors was decreased after Ro 5-4864 and PK 11,195 treatments in the olfactory bulb but not in the cerebral cortex. The chronic treatment with peripheral BZ receptor ligands Ro 5-4864 and PK 11,195 produced only little behavioral effects. Ro 5-4864, often presented as an agonist of peripheral BZ receptors, was behaviorally inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Amygdala kindling increased fear-response, but did not impair spatial memory in rats.

The behavioral effects of amygdala kindling, a model of experimental epilepsy in rats, are reported. The animals were stimulated twice a day until stage 5 (generalized clonic) seizures were obtained three times. Two weeks later the performance of the amygdala-kindled and sham-operated rats was tested in the open-field test, on the elevated plus maze, elevated bridges, and in the Morris water maze. The results show that amygdala kindling decreased exploratory and other motor activity in the open-field test, had anxiogenic effects on the elevated plus-maze, decreased boldness on the elevated bridges, but had a negligible affect in the spatial memory task. These results suggest that amygdala kindling affects the normal fear reaction of rats, a response that is known to be mediated through the amygdaloid pathways.

Amygdala↗

PubMed1992

Puffing behavior during the smoking of a single cigarette in a naturalistic environment.

The 36 participants in this study were habitual low-yield cigarette smokers, medium-yield cigarette smokers, and switchers from medium- to low-yield cigarettes. All participants smoked both low- (0.4 mg) and medium-nicotine (0.9 mg) cigarettes during the study. Puffing indices were recorded during the first two cigarettes, after an overnight abstinence of smoking, by a portable flowmeter processor unit in a naturalistic environment. The puff volumes per cigarette and per day were significantly lower while switching to higher-yield cigarettes, mainly due to a decrease in the number of puffs and longer interpuff intervals, but also due to a decline in puff duration and flow rate. However, the downregulation by puff volume was incomplete, at most two thirds, as calculated by machine smoking yields. Within the course of smoking a single cigarette, the flow rate was quite stable, puff duration and puff volume decreased toward the end of the cigarette, and interpuff interval was longest during the middle of the cigarette. Total puff volumes per cigarette were similar in the first two cigarettes of the day after an overnight abstinence of smoking, with no significant differences in other puff parameters. Diurnal cotinine excretion revealed that nicotine titration in switching situations was very accurate among switchers and medium-yield cigarette smokers, but not among the low-yield cigarette smokers, and so called oversmoking was found with the higher-nicotine brand. Preferred cigarette type had little effect on the puffing patterns of smokers in single cigarettes.

Adult↗

PubMed1992

Ethanol and delta-sleep-inducing peptide: effects on brain monoamines.

The brain content of dopamine (DA) and its metabolites [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were the same in rats with different immobilization times in forced swimming test, while the serotonin (5-HT) concentration was higher in high active (HA, immobilization < 2 min) than low active (LA, immobilization > 5 min) animals. Ethanol (2 g/kg, PO) tended to increase the DA level in the striatum and nucleus accumbens in LA rats and decrease the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentration in HA rats. delta-Sleep-inducing peptide (DSIP) injection reduced the level of 5-HT in the medial prefrontal cortex (MFC) in both groups, did not affect the concentration of DA or DOPAC, but increased HVA in the striatum of HA rats. DSIP injected before ethanol administration augmented the ethanol effects on 5-HT in the MFC and attenuated the action of ethanol on 5-HIAA in the nucleus accumbens. A relationship between the different levels of voluntary alcohol consumption and sensitivity to stress among LA and HA rats and the differences in DA and 5-HT concentrations is suggested. The use of LA and HA rats in developing models for testing of stress-shielding compounds is also described.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Effects of smoking abstinence and chain-smoking on puffing topography and diurnal nicotine exposure.

Effects of chain-smoking, a 15-h smoking abstinence, and the nicotine yield of cigarettes on puff indices were studied in eight healthy smokers by using a controlled crossover study design. Puff parameters were measured puff by puff with a portable measuring device when 10 or 20 cigarettes, with nicotine yields of 0.3 and 1.0 mg, were smoked per day. The interval between sessions was 1 h, and the 20 cigarettes per day were chain-smoked 2 at a time. Serum cotinine indicated that smokers compensate completely for the lower nicotine delivery from the 0.3-mg cigarette. Smokers almost doubled total puff volume per cigarette and per day mainly by taking more puffs from the low-nicotine cigarettes and slightly prolonging puff duration. However, nicotine deprivation and chain-smoking had a relatively minor effect on puffing indices with both brands, a fact that agrees poorly with the nicotine titration hypothesis. However, in the course of every single cigarette of the day smokers significantly reduced puff duration and puff volume toward the end of the cigarette, which probably involves satiation of the nicotine crave but may also be due to changes in taste of the smoke.

Adult↗

PubMed1991

Smoking behavior in low-yield cigarette smokers and switchers in the natural environment.

Urinary cotinine and puffing parameters were studied in 36 smoking students. Three smoking groups, formed according to the tar content of their preferred cigarette, were compared. Eighteen students had always smoked low-yield, 10 medium-yield and 8 were switchers from medium- to low-yield cigarettes. The subjects smoked their preferred brand (the first week), low-yield cigarettes (the second week) and medium-yield cigarettes (the third week). Day urine samples were collected for cotinine analysis during the two last days of the test weeks. Puffing indices were reported on the last day of every test week with a portable microcomputer assisted analyzer with flowhead cigarette holder. Urinary cotinine concentrations were rather constant within the groups, but lower among the low-yield cigarette smokers as compared to the switchers (p less than 0.05). Also the female smokers had lower cotinine concentrations than the male smokers (p less than 0.05). The compensatory behavior seen in every smoking group while they were smoking low-yield cigarettes was based on up-regulation in single puff volume, puff duration and total smoking time when compared to values with medium-yield cigarettes. The correlation between cotinine concentration and diurnal puff volume (1/day) was poor. It is concluded that the benefit possibly gained with low-yield cigarettes is not long lasting.

Adult↗

PubMed1991

Evoked field responses, recurrent inhibition, long-term potentiation and immobility-related nonrhythmical EEG in the dentate gyrus of fimbria-fornix-lesioned and control rats.

The effects of complete fimbria-fornix (FF) lesioning, bilateral medial-FF lesioning and systemic administration of a novel noradrenergic alpha 2-antagonist, atipamezole, on electrophysiological properties of the hippocampal formation were studied in the rat. In the hilus of the dentate gyrus (DG) complete FF lesioning abolished the long-term potentiation (LTP) of the population spike (PS), which in control rats could be induced by the application of high-frequency stimulus trains on the medial perforant pathway (PP). Several other electrophysiological properties examined in the medial-FF-lesioned rats changed as well. These changes included a decrease in the efficacy of recurrent inhibition and slight differences in granular cell population response evoked by perforant path stimulation. Also, in the DG the power of awake immobility-related nonrhythmical electroencephalogram (EEG) was significantly lower in FF-lesioned rats than in controls. In the DG of control rats systemic administration of atipamezole (1 mg/kg) shifted the population spike-field postsynaptic potential response curve towards the left. In FF-lesioned rats this drug had no effects. The slight effects of atipamezole would be in line with earlier studies, which have shown that noradrenergic activation facilitates neuronal transmission in the DG. Possible explanations for the changes seen in FF-lesioned rats include deafferentation of different subcortical projections and increased epileptic activity. These established changes in synaptic plasticity, recurrent inhibition, nonrhythmical EEG and evoked responses would indicate that information processing is severely hampered in the first stage of the hippocampal trisynaptic circuit after fimbria-fornix lesioning. Thus, the results show that aminergic/cholinergic projections have a significant role in information processing in the dentate gyrus of hippocampal formation.

Adrenergic beta-Antagonists↗

PubMed1991

Modulation of EEG rhythmicity and spike activity in the rat hippocampus by systemically administered tetrahydroaminoacridine, scopolamine and atipamezole.

The hippocampal EEG recording electrodes were implanted bilaterally in the hilus of the dentate gyrus (DG) and the stratum radiatum layer of the CA1 area in young (2-3-month-old) and aged (17-20-month-old) rats. In the subgroups of rats, brain noradrenaline (NA) was depleted by DSP-4 neurotoxin (50 mg/kg, IP). The aged animals were included in DSP-4-lesioned group in order to diminish the plastic regeneration of the noradrenergic system which may be more effective in young subjects. All the EEG recordings, after the administration of different agents or vehicle, were made while rats were awake and immobile. Approximately 40% decrease of brain NA had no noticeable effects on the nonrhythmical hippocampal EEG in either age group. In all the rats, compared to the baseline recordings, scopolamine hydrobromide (2 mg/kg, IP, a muscarinic antagonist) increased the incidence of spontaneous EEG spikes, while tetrahydroaminoacridine (THA, 12.5 mg/kg, IP, an acetylcholine esterase inhibitor) decreased the spike activity and induced theta rhythm. Atipamezole (3 mg/kg, SC), a noradrenergic alpha 2-antagonist, increased the baseline amplitude of the nonrhythmical EEG in the DG and increased slightly the spike activity in the CA1 area. The combined blockade of muscarinic receptors by scopolamine (2 mg/kg) and noradrenergic alpha 2-receptors by atipamezole (3 mg/kg) resulted in irregular EEG pattern and corresponding power spectra differed from the scopolamine spectra. The last combination treatment suggests that the effect of atipamezole was not mediated by the secondary cholinergic activation. In the DG, the spectral power increase caused by atipamezole may be related to the increased excitability/bursting liability of granular cells because NA turnover is increased by this agent and NA increases the excitability of granular cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗