PubMed Health⌕ Search

Biomedical subjects

I Hilakivi

Publications and source records attributed to I Hilakivi.

At least 19 recordsLinked to original sources

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↗

Strain difference in early postnatal sleep-wake behaviour between Alko Alcohol and Wistar rats.

Early postnatal sleep-wake behaviour of male and female rats of Alko Alcohol and Wistar strain was studied using a static charge sensitive mattress when the rats were aged 1 and 2 weeks postnatally. In both strains and sexes, waking time relative to total recording time increased, proportion of quiet state did not change, and that of active sleep decreased during the second postnatal week. The number of long active sleep stages relative to short active sleep stages and the duration of sleep-wake stages increased with age. Transitions between quiet state and active sleep became fewer with increasing age. Waking time increased more in Wistar rats than in Alko Alcohol rats. At 1-2 weeks of age, the percentage of active sleep and the number of long active sleep stages relative to short active sleep stages were larger, and the duration of sleep-wake stages longer in Alko Alcohol than in Wistar rats. Sleep-wake behaviour did not differ between the sexes of either strain or age. Selective breeding for high alcohol preference in Alko Alcohol rats may have caused a genetic trait in early postnatal sleep-wake behaviour.

Age Factors↗

Early postnatal antidepressant treatment and juvenile stereotyped behaviour in rats.

The effect of antidepressants on stereotyped behaviour in rats during development was examined. Rats were injected s.c. once a day from the 6th to the 22th day after birth with 0.9% sodium chloride, with desipramine 5 mg/kg body weight, with nomifensine 10 mg/kg, or with zimelidine 25 mg/kg. Stereotyped behaviour was assessed when the rats were 1 month and 2 months of age. Desipramine intensified and prolonged apomorphine 0.5 mg/kg induced stereotyped behaviour at 1 month but not at 2 months of age. Nomifensine and zimelidine did not affect stereotyped behaviour at either 1 month or 2 months of age. Thus, 2-week treatment with desipramine during early development was shown to increase stereotyped behaviour at a juvenile age.

Animals↗

Alertness and sleep in young men during military service.

Alertness and sleep in healthy young men conscripted into military service were examined by testing personality characteristics and by completing questionnaires at the beginning of military service about their civilian life alertness and sleep, and by using polygraphic recordings during their military service. Sleep-time during service was restricted to 8 hours a night; 236 men answered the questionnaire on civilian life alertness and sleep; 116 men a Minnesota multiphasic personality inventory; 7 underwent conventional, and 29 static charge-sensitive bed sleep recordings. Daytime latencies to Stage 2 sleep were 11 +/- 2 min. Sleep latencies were the shortest 6 h after waking. Night sleep was normal in conventional recordings. Nocturnal activities in static charge-sensitive bed recordings were: motor-active waking 4 +/- 3%, active sleep 24 +/- 11%, intermediate sleep 22 +/- 8%, quiet sleep 47 +/- 13%, and undefined 4 +/- 2%. Positive answers to questions on civilian life sleepiness were related to high scores on scales for hypochondria, psychasthenia and sense of reality, and night sleep longer than 10 h to high scores for psychasthenia and sense of reality, but not to polygraphic measures. Two men with complaints about civil-time irresistible sleep at the time of beginning the military service had short Stage 2 latencies at the daytime minimum of alertness during service (4 and 8 min). Although alertness and sleep during military service were normal on average, the findings suggest that all conscripted individuals may not have had enough sleep.

Adult↗

A sixteen-factor personality test for predicting automobile driving accidents of young drivers.

The predictive value of the Cattell 16-factor personality test on the occurrence of automobile accidents among conscripts during their 11-month military service in a transportation section of Finnish Defense Forces was examined. Automobile driving experience before and during the follow-up as well as the occurrence of traffic accidents and penalties before and during the follow-up period were investigated. Complete data on personality, mileage, and traffic accidents plus penalties were obtained for 597 conscripts. In this population, altogether 91 automobile accidents were recorded for 82 conscripts. A logistic model showed that impulsivity and adventurousness (high score in factor H), naivete and excessive trustfulness (low score in factor L), and poor self-control (low score in factor Q3) predicted significantly, and guilt proneness and depression (high score in factor O) almost significantly the subsequent occurrence of motor vehicle accidents. Factors L and Q3 remained significant when only accidents of which the subject was found guilty were being predicted. All these personality factors are related to the control of emotions. The results indicate that the 16-factor personality test is valuable when selecting safe drivers in a population of young male adults with little previous driving experience.

Accidents, Traffic↗

Effects of kynurenic acid and ketamine on neonatal sleep in rats.

Kynurenic acid and ketamine are, besides non-specific actions, antagonists of excitatory acidic amino acids in the rat brain. At intraperitoneal doses of 300 mg/kg (1.6 mmol/l) and 5 mg/kg (18 mmol/l), respectively, they are equipotent antagonists of N-methyl-D-aspartate receptors. We studied the acute effects of ketamine and kynurenic acid, at these doses, on sleep patterns of rats during the second and third postnatal weeks with the so called static charge sensitive mattress (SCSB). Both kynurenic acid and ketamine decreased active sleep; ketamine additionally increased quiet state and kynurenic acid increased waking. The decrease in active sleep may be related to glutaminergic NMDA and serotonergic responses in the rat brain but non-specific actions and interactions with other transmitter systems are also involved.

Animals↗

Early postnatal treatment with propranolol affects development of brain amines and behavior.

The present study examined the effects of early postnatal treatment with a beta-adrenoceptor antagonist propranolol (5 mg/kg IP daily) on concomitant and subsequent behavior and central aminergic transmission in rats. During propranolol exposure from the 7th to the 20th postnatal days sleep-wake recordings, carried out with the static charge sensitive bed (SCSB) method, showed a decrease in the percentage of active sleep and an increase in waking. When the animals were 1-3 months of age, the open field behavior was changed, immobility time in the Porsolt's swim test was lengthened, and voluntary alcohol consumption was increased in the propranolol-treated rats. Neither motor reactivity to auditory stimuli nor spontaneous alternation behavior was affected. At the age of 4 months concentrations of brain amines and their metabolites were measured from several brain regions. In the propranolol-treated rats the noradrenaline levels were increased in the limbic forebrain and cerebellum. The results suggest that in rats the exposure to propranolol during the rapid growth period of cerebral catecholamine systems, and the concomitant alterations in sleep are related to later changes in behavior and to increased noradrenaline content in the limbic forebrain and cerebellum.

Acoustic Stimulation↗

Neonatal treatment with monoamine uptake inhibitors alters later response in behavioural 'despair' test to beta and GABA-B receptor agonists.

The administration of monoamine uptake-inhibiting antidepressant drugs to rats during the early postnatal period was previously shown to lengthen the duration of subsequent immobility in Porsolt's swim test, hence suggesting increased behavioural 'despair' in these animals. Because the mechanism of the antidepressant action may be related to changes in the cerebral monoamine or gamma-aminobutyric acid (GABA) function, the present study was carried out to examine the response in the swim test to a beta-receptor agonist salbutamol, or to the GABA-B receptor agonists progabide and baclofen in rats treated with antidepressant drugs during the second and third postnatal week: either desipramine 5 mg/kg, nomifensine 10 mg/kg or zimeldine 25 mg/kg. When tested a month later i.e. at the age of two months these rats were immobile in water for a longer period than the controls. Salbutamol 10 mg/kg and progabide 100 mg/kg increased the immobility time in the control rats but neither drug affected the rats treated with desipramine, nomifensine or zimeldine. When the animals were 5 months of age, salbutamol 10 mg/kg and baclofen 10 mg/kg shortened the immobility time in the desipramine-treated rats. The control rats and those treated with zimeldine were not affected by the drugs. The results indicate that in the rats which were neonatally treated with antidepressants, the immobility time in water is lengthened in adulthood. Moreover, the response to beta-receptor and GABA-B receptor agonists is increased from the response observed in the control rats.

Albuterol↗

Early postnatal deprivation of active sleep with desipramine or zimeldine impairs later behavioural reactivity to auditory stimuli in rats.

To examine the functional significance of early postnatal active sleep for the development of behavioural reactivity to auditory stimuli, rat pups were daily injected i.p. from the 7th to the 18th postnatal days with 5 mg kg-1 (6.6 mmol l-1) desipramine or 25 mg kg-1 (12.2 mmol l-1) zimeldine. Sleep-wake behaviour was recorded with a static-charge-sensitive bed (SCSB) method. Both desipramine and zimeldine suppressed the percentage of active sleep relative to the total recording time throughout the treatment period. In addition, these drugs increased the percentage of quiet state and waking. At the age of 38 days the zimeldine-treated rats showed more motor activity in the open field than the controls. At the age of 39 and 78 days all rat groups behaved similarly in the open field. Startle measures and motor activation, provoked by auditory stimulation, were determined by the SCSB method when the rats were 4 months of age. Auditory stimuli, consisting of a series of ten clicks, induced a greater number of startles as well as strong movement responses in the control rats than in the desipramine- or zimeldine-treated rats. The number of small movement responses did not differ between the rat groups. These findings indicate that early postnatal active sleep and the monoaminergic systems regulating it may be important for the normal development of neuronal circuitry associated with later reactivity to auditory stimuli.

Acoustic Stimulation↗

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↗

Effect of phentolamine on wakefulness and sleep during recovery from REM sleep deprivation in cats.

Adult cats with permanent EEG, EMG, EOG, and PGO electrodes were recorded for 24 hours started at the end of a 72-hour REMS deprivation induced by a platform-water-tank procedure and after receiving IP injections of phentolamine (20 mg/kg) or saline. Exposure of the cats to the platform-REMS deprivation procedure increased the percentage of REMS during the subsequent 24 hours. Phentolamine interacted with the platform REMS deprivation causing the peak of REMS percentage to occur during recovery hours 5-12. These findings indicate that blockade of alpha-receptors has an additive effect on platform-REMS deprivation induced REMS rebound in cats.

Animals↗

Increased adult behavioral 'despair' in rats neonatally exposed to desipramine or zimeldine: an animal model of depression?

Occurrence of depressive behavior at mature age was studied in rats exposed neonatally to antidepressant drugs. Early antidepressant treatments have been shown to increase voluntary alcohol consumption and the percentage of rapid-eye-movement (REM) sleep relative to total sleep time in adult rats as well as to cause long-lasting reduction in the concentrations of monoamines in the forebrain. In the present study rats were daily given either 5 mg/kg desipramine or 25 mg/kg zimeldine from the 7th to the 18th postnatal days. When they were 2 months and 5 months of age behavioral 'despair' was studied by using a modified version of Porsolt's swim-test. At both ages the desipramine-treated and zimeldine-treated rats expressed lengthened immobility times in the water pail. The findings indicate that neonatal exposure of rats to desipramine or zimeldine induces behavioral 'despair' at mature age. Thus, early exposure of rats to antidepressants causes long-lasting behavioral disorders, and, moreover, may be used to devise an animal model of subsequent depression.

Animals↗

Effects of serotonin and noradrenaline uptake blockers on wakefulness and sleep in cats.

The aim of the study was to examine the role of serotonergic (5-HT) and noradrenergic mechanisms in the regulation of wakefulness and sleep. For this purpose, adult cats with implanted electrodes for EEG, EOG and EMG were exposed to the 5-HT uptake blocker citalopram (0.1, 0.5 and 5.0 mg/kg intraperitoneally) and the noradrenaline uptake blocker prindamine (5 mg/kg intraperitoneally) at the start of continuous 16-hour sleep-wake recordings. Citalopram increased deep slow wave sleep and decreased REMS. Also prindamine decreased REMS but initially increased the proportion of time spent in the state of active wakefulness. Furthermore, to examine the interactions between 5-HT-nergic and noradrenergic mechanisms in the regulation of sleep, the administration of citalopram was preceded by intraperitoneal injections of phentolamine (10 mg/kg), an alpha-antagonist, and propranolol (5 mg/kg), a beta-antagonist. Phentolamine was totally ineffective against citalopram whereas propranolol partially counteracted the effects of citalopram on sleep. Prindamine was combined with the alpha-antagonists yohimbine (1 mg/kg), phentolamine (10 mg/kg) and prazosin (1 mg/kg) or with the beta-antagonist propranolol (5 mg/kg). Yohimbine was without any effect on REMS, phentolamine partly antagonized prindamine-induced decrease in the percentage of REMS, and prazosin only prolonged REMS latency and reduced deep SWS as well. Propranolol partially antagonized the prindamine-induced initial increase in active wakefulness time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neonatal antidepressant administration suppresses concurrent active (REM) sleep and increases adult alcohol consumption in rats.

Neonatal administration of desipramine, nomifensine and zimeldine suppressed concurrent active sleep and led to increased preference of alcohol as well as decreased concentrations of monoamines in the brain in adult rats. The findings suggest that early postnatal active sleep and the monoaminergic transmission regulating it are related to adult alcohol consumption.

3,4-Dihydroxyphenylacetic Acid↗

Biogenic amines in the regulation of wakefulness and sleep.

Neurophysiological, neurochemical and neuropharmacological evidence indicates that cerebral monoamines are important regulators of wakefulness and sleep besides cerebral amino acid-ergic and peptidergic systems. The cerebral monoamines noradrenaline, dopamine and acetylcholine are positively involved in electroencephalographic aspects of waking and paradoxical or REM sleep. A high level of noradrenergic transmission facilitates waking, and a lower, moderate level facilitates REM sleep. Serotonin is involved in the regulation of synthesis, storage and release of sleep inducing factors, and in the gating mechanisms of REM sleep. Histamine neurons play a role in the regulation of vigilance during waking state. These neurotransmitter systems are important targets for drug actions.

Acetylcholine↗

Effect of prenatal alcohol exposure on neonatal sleep-wake behaviour and adult alcohol consumption in the AA and ANA rat lines.

To study the role of genetic factors in the effects of prenatal alcohol exposure on behaviour, dams of two rat lines developed to differ in voluntary alcohol intake, alcohol-preferring (AA) and alcohol-avoiding (ANA) rats were given a 5-10% alcohol solution mixed with a 1% sucrose solution as a sole drinking liquid throughout gestation. Sleep-wake behaviour of the offspring was studied at the ages of 7, 14 and 20 days, using a movement-sensitive mattress. In ANA rats, sleep recordings showed that prenatal alcohol exposure increased the percentage of waking but decreased the percentage of active sleep. Sleep-wake behaviour of the AA rats was not affected by alcohol exposure in utero. Prenatal alcohol exposure did not change open field behaviour in 1 month old rats, except that the alcohol-exposed AA rats' defaecation was decreased. When rats were 3 months old, voluntary intake of 10% (v/v) alcohol increased for alcohol-exposed ANA rats and decreased for alcohol-exposed AA rats as compared to the controls. The results indicate that AA rats may compensate for the effects of prenatal alcohol exposure on behaviour, whereas offspring of the alcohol-exposed ANA dams suffer from severe behavioural disturbances. These findings further suggest that genetic factors are responsible for the differences in the susceptibility of rat foetuses to alcohol-induced long-term effects on behaviour.

Alcohol Drinking↗

Validation of the cuff pedestal technique for rapid eye movement sleep (REMs) deprivation by electrophysiological recordings.

Twenty-four-hour recordings of electrophysiological correlates of the sleep-waking cycle in the rat were performed during different stages of cuff pedestal treatment. It was found that rats adapted to live on pedestals with the cuff raised displayed undisturbed patterns of sleep and wakefulness. Lowering the cuff for three days resulted in virtually total disappearance of rapid eye movement sleep (REMs), while slow wave sleep (SWs) was only slightly reduced. Raising the cuff induced a prominent rebound increase of REMs. These results accord with data obtained by means of the conventional flowerpot procedure and corroborate the validity of the cuff pedestal technique.

Animals↗