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Biomedical subjects

E Hård

Publications and source records attributed to E Hård.

At least 19 recordsLinked to original sources
PubMed1996

Facilitation of ethanol consumption by intracerebroventricular infusions of corticosterone.

Male Wistar rats bearing intracerebroventricular (ICV) cannulae and with simultaneous access to 6% ethanol and water were subjected to adrenalectomy (ADX) or sham surgery. ADX decreased ethanol intake. Starting a few days later, the animals received ICV infusions with 100 micrograms corticosterone acetate (CORT) with 2-to 3-day intervals for 2 weeks. ICV CORT, but not SC CORT at the same dose, restored ethanol consumption in ADX rats to preoperative levels, whereas vehicle infusions (propylene glycol) did not. Adrenally intact animals, which normally consumed moderate amounts of ethanol (approximately 0.5 g/kg per day), also showed a robust effect of ICV infusions of CORT, whereas this facilitatory effect was not observed in high consumers (approximately 3.0 g/kg per day). The suppressive effect of ADX on ethanol intake was not reproduced by concurrent and repeated ICV infusions of intracellular mineralocorticoid (RU 28318) and glucocorticoid (mifepristone) receptor blockers. It is concluded that CORT stimulates alcohol consumption by acting in the brain, probably by way of neuronal membrane mechanisms.

Adrenalectomy↗
PubMed1995

Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat, and the effect of type I and type II corticosteroid receptor antagonists.

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.

Adrenalectomy↗
PubMed1995

Significance of adrenal corticosteroid secretion for the food restriction-induced enhancement of alcohol drinking in the rat.

Male Wistar rats with continuous access to 6% ethanol solution and water in their home cages were subjected to food restriction (FR). Reduction of body weight to 80% of normal was associated with a significant increase in ethanol drinking. It is known that the stress of FR gives rise to increased corticosterone secretion, and in line with these findings it was found that the weight of the thymus (whose size is inversely related to corticosterone levels) was reduced to 55% of normal in the present FR rats. Two subsequent experiments indicated that this adrenal activation contributed to the FR-induced enhancement of alcohol drinking. Firstly, adrenalectomized rats showed no evidence of enhanced alcohol drinking during food restriction, suggesting that adrenal corticosterone hypersecretion contributes to the enhanced ethanol consumption during FR. Secondly, treatment of FR rats with the enzyme inhibitor cyanoketone, which blocks stress-induced but not basal corticosterone secretion, at least partly prevented the FR-induced increase in ethanol drinking. These results add further evidence that sustained exposure to corticosterone facilitates ethanol consumption in the rat.

Adrenal Cortex Hormones↗
PubMed1994

Effects of ventral striatal 6-OHDA lesions or amphetamine sensitization on ethanol consumption in the rat.

Female rats with continuous access to water and 6% ethanol were given bilateral ventral striatal 6-OHDA infusions, which induced pronounced striatal depletions of dopamine. The postoperative ethanol consumption of these rats was not significantly affected in comparison to vehicle-infused controls. In a second experiment, female rats received escalating doses of d-amphetamine over a 5-week period (from 1 to 9 mg/kg/injection). Control females were given saline injections. Following a 3-month drug-free interval, the females were given access to ethanol, the concentration of which was gradually increased from 2% to 12% with weekly intervals. Amphetamine-sensitized rats consumed significantly more alcohol than the saline-treated controls. Taken together, these results suggest that striatal dopaminergic mechanisms, while not necessary for basal ethanol drinking, can facilitate alcohol drinking.

Alcohol Drinking↗
PubMed1994

Metyrapone-induced suppression of corticosterone synthesis reduces ethanol consumption in high-preferring rats.

The fluid intake of male Wistar rats with simultaneous access to water and 6% ethanol was determined between 0900 and 1500 h. In high-preferring males (normally covering > 60% of their daily fluid consumption in the form of ethanol), two injections with the corticosterone synthesis inhibitor metyrapone (50 mg/kg) at 0900 h and 1200 h for 4 consecutive days significantly reduced ethanol preference such that they preferred water over alcohol. Treatment with corticosterone (0.6 mg/kg) 2 h before each metyrapone injection partially cancelled this effect of the synthesis inhibitor. By contrast, there was no significant effect of metyrapone treatment on the drinking of ethanol in low-preferring rats (normally covering < 30% of their daily fluid consumption in the form of ethanol). These results suggest that the adrenal secretion of corticosterone directly or indirectly modulates the intake of alcohol in high-preferring rats.

Alcohol Drinking↗
PubMed1994

Effect of citalopram on alcohol intake in heavy drinkers.

The effect of the selective serotonin reuptake inhibitor citalopram (40 mg daily dose) on alcohol intake was investigated in a double-blind, placebo-controlled cross-over study. Thirty men with heavy alcohol consumption (mean daily alcohol intake 111 +/- 51 g pure alcohol) completed the study. After a 2-week baseline period, subjects were randomly allocated to treatment with either citalopram or placebo for 5 weeks. In the total sample of heavy drinkers, no difference was found between citalopram and placebo treatment in alcohol consumption or days of abstinence. However, the response to citalopram was negatively correlated (rs = -0.67, p < 0.01) with baseline levels of mean daily alcohol intake. Therefore, we divided the total sample into two subgroups with baseline mean daily alcohol intake above and below median (107 g pure alcohol), respectively. In the group with the higher baseline values (138 +/- 25 g pure alcohol), citalopram was not different from placebo in reducing the daily alcohol intake, but in subjects with the lower baseline values (85 +/- 15 g pure alcohol), citalopram was significantly (p < 0.01) superior to placebo. Consequently, citalopram at the present dose appears capable of reducing alcohol intake only in a subgroup of heavy drinkers with a mean daily consumption of between 60 and 100 g pure alcohol.

Adult↗
PubMed1989

Effects of chronic and acute ethanol treatment during prenatal and early postnatal ages on testosterone levels and sexual behaviors in rats.

This study was prompted by previous findings that prenatal ethanol exposure may interfere with the differentiation of the sexual behavior in rats. Ethanol (6 g/kg) administered daily from day 15 postconception, resulted in elevated testosterone (T) levels on Day 18 in male and female fetuses. No alterations of sexual behavior in the ethanol-treated male offspring were seen under these conditions. However, in ethanol-treated female offspring the onset of regular estrous cycling was significantly delayed. Acute treatment with doses of ethanol, 2, 4 or 6 g/kg, was ineffective in influencing plasma T levels of the fetuses. Acute treatment with 3 g/kg ethanol did not prevent the rise of T levels normally occurring immediately after birth. In adulthood, but not at prepubertal age (Day 30), treatment of male rats with 2 g/kg ethanol caused a depression of plasma T levels. Possible mechanisms affected by ethanol exposure and influencing on the fetal development were discussed.

Age Factors↗
PubMed1988

Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists.

In the present series of experiments we have studied the effects of the dihydropyridine calcium channel antagonist nifedipine on ethanol-induced changes in behavior and dopamine (DA) release and metabolism. The locomotor-stimulatory effect of low doses of ethanol (2.5 g/kg) was antagonized by nifedipine, whereas ethanol-induced sedation observed after higher doses (4.5 g/kg) was potentiated. Biochemical studies indicated that ethanol enhanced the metabolism and release of DA in the striatum and the DA-rich limbic regions measured by post mortem analyses of DA-metabolites by HPLC with electrochemical detection and by in vivo voltammetry in anaesthetized rats, respectively. Pretreatment with nifedipine antagonized the stimulatory effects of ethanol on the DA-system. Nifedipine reduced the preference for ethanol, estimated by the relative intake of ethanol (6% v/v) and water in a free-choice situation, suggesting an influence of nifedipine not only on the stimulatory but also on the positive reinforcing effects of ethanol. The present results suggest that the locomotor-stimulatory and positive reinforcing effects of ethanol as well as its enhancing effect on dopaminergic activity may involve an enhancement of calcium mediated mechanisms.

Animals↗
PubMed1988

Effect of clonidine on ultrasonic vocalization in preweaning rats.

The present study was undertaken to investigate the involvement of the noradrenergic neurotransmission system in the ultra sonic callings emitted by rat pups separated from their mother and exposed to cold stimulation. The investigation was primarily performed by help of agents selectively affecting the alpha-adrenoceptors: the alpha 2-agonist clonidine, the alpha 1-antagonist prazosin and the alpha 2-antagonist idazoxan. Clonidine dose-dependently stimulated the amount of ultra sonic vocalization, an effect not solely dependent upon the effect of clonidine on body temperature. In a developmental study it was found that clonidine uniformly stimulated crying at all ages from 4 days of age up to 18 days of age, that is during the whole preweaning period. Clonidine stimulated ultrasonic crying in rat pups, devoid of presynaptic catecholamine (CA) neurons by combined pretreatment with the monoamine depletor, reserpine, and the inhibitor of CA-synthesis, alpha-methyl-tyrosine. This finding suggested that the stimulating effect of clonidine on ultrasonic vocalization was mediated by postsynaptic adrenoceptors. In pups, 12 days of age, idazoxan blocked the effect of cold stimulation on ultra sonic crying, suggesting that alpha 2-adrenoceptors, presumably postsynaptic ones, mediated this kind of stimulation. Idazoxan also antagonized the effect of clonidine, but only at a dose effective also in control pups. Prazosin had no effect on cold-stimulated crying, but antagonized the effect of clonidine, suggesting that the effect of clonidine was also mediated by alpha 1-receptors. At 18 days of age, prazosin no longer antagonized the effect of clonidine, whereas the antagonizing action of idazoxan was reinforced. The age-dependent variation in responsiveness to the adrenergic drugs suggest maturational changes in the function of the CA-system occurring between 12-16 days of age.

Adrenergic alpha-Antagonists↗
PubMed1988

Effects of 8-OH-DPAT on ultrasonic vocalization and audiogenic immobility reaction in pre-weanling rats.

Emotional reactivity in preweanling rats was assessed by observations of two reactions characteristic for two different age periods, respectively. One reaction, ultrasonic vocalization in rat pups separated from mother and littermates, was observed during early postnatal age (10 days). The other reaction, rigid immobility elicited by a sudden sound, was observed at the age of weaning (20 days). Previous studies from this laboratory indicated that the serotonergic system was involved in the control of both of these reactions. In the present study this notion was further tested by investigating the effects on these reactions of the congener of ergot 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), characterized as a centrally-acting, potent and selective agonist of 5-hydroxytryptamine (5-HT). Rat pups, 10 days of age, were treated subcutaneously with 7.5, 15 and 30 micrograms/kg of 8-OH-DPAT and subsequently tested for ultrasonic vocalization. Animals, 20 days old, were treated with 15, 30 and 60 micrograms/kg of 8-OH-DPAT before testing of the immobility reaction. The results showed a dose-dependent decrease of the amount of ultrasonic vocalization and of the duration of the immobility reaction, indicating an anxiolytic-like action of 8-OH-DPAT in both behavioural patterns. A possible explanation for the antagonistic effect of 8-OH-DPAT is that this drug exerts a preferential agonistic effect on presynaptic (auto-) 5-HT receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Effects of diazepam, ethanol and Ro 15-1788 on ultrasonic vocalization, locomotor activity and body righting in the neonatal rat.

It has been suggested that ethanol, besides its stimulating, sedative and ataxic effects, also exerts anxiolytic effects similarly to diazepam. In the present study we tested this hypothesis on ultrasonic distress crying in neonatal rats separated from mother and litter-mates. The results showed that both ethanol and diazepam reduced crying in a dose-dependent manner and at doses not affecting the level of motor activity. It was found that the effects of diazepam, but not that of ethanol, was antagonized by the specific benzodiazepine-receptor-antagonist Ro 15-1788. The effects of ethanol were antagonized by the GABA-ergic antagonist picrotoxin. Assessing the sedative/ataxic effects of ethanol and diazepam by the surface body righting response, it was found that the effect of diazepam, but not of ethanol, was antagonized by Ro 15-1788. The results support the hypothesis that ethanol exerts similar anxiolytic actions as diazepam, but that the effects are mediated by different mechanisms.

Animals↗
PubMed1985

Effect of diazepam, apomorphine and haloperidol on the audiogenic immobility reaction and on the open field behavior.

Weanling rats were treated with diazepam, apomorphine, and haloperidol to study the influence of the dopamine (DA) system on the audiogenic immobility reaction and open field locomotory behavior. Treatment with diazepam (0.025, 0.05, and 0.1 mg/kg) caused a dose-dependent shortening of the duration of the immobility response. Treatment with apomorphine (0.125, 0.25, and 0.50 mg/kg) shortened both the immobility reaction and the latency to leave the spot where the animal was first placed in the open field (latency for first crossing). Locomotor activity increased in a dose-dependent fashion. Both grooming and rearing showed biphasic dose response curves, with a maximum occurring at the 0.125 mg/dose for grooming and at the 0.25 mg/dose for rearing. Haloperidol (0.06 mg/kg) exerted opposite effects to those of apomorphine, but also produced increased running during the auditory stimulation (flight distance). Using the immobility reaction as an expression of fear, we concluded that activation of the DA system decreases while inhibition of the DA system increases fear. It was hypothesized that the DA system exerts an inhibitory function in the expression of fear.

Acoustic Stimulation↗
PubMed1985

Behavioral reactivity in spontaneously hypertensive rats.

Spontaneously hypertensive rats of the Okamoto strain (SHR) were compared with inbred normotensive rats of the Wistar-Kyoto strain (WKY) and with normally bred Wistar rats (NT) in tests on the audiogenic immobility reaction (freezing), open-field behavior in a dark and an enlightened arena respectively, auditory startle response and male sexual behavior. Compared to the WKYs the SHRs showed increased locomotion and rearing in the open-field situations, reduced startle response and shortened immobility reaction. The SHRs differed in the same way from the NT rats with the exception for motor activity in the dark arena, where no differences were observed. The WKY rats showed less motor activity than the NT animals. Both SH and WKY rats showed shorter latency time for ejaculation than the NT rats. The characteristics of the behavior patterns displayed by the SH rats were interpreted as indicating a reduced propensity for fear reactions in this strain of rats compared to the WKY and NT strains used in the present study.

Acoustic Stimulation↗
PubMed1985

Impaired maternal behaviour and altered central serotonergic activity in the adult offspring of chronically ethanol treated dams.

Female rats were given 16% ethanol solution as the sole liquid during the entire period of gestation. At birth the offspring was removed and reared by foster dams consuming normal tap water. At adult age the female offspring showed deficiencies in their maternal behaviour; they built nests of poor quality and they displayed prolonged times for retrieving pups placed outside the nest. In the whole brains of the prenatally ethanol-exposed females a decreased serotonin synthesis was observed. The offspring of the prenatally ethanol exposed mothers did not show any signs of disturbances in physical or behavioural development.

Animals↗
PubMed1985

Effects of maternal ethanol consumption on the offspring sensory-motor development, ultrasonic vocalization, audiogenic immobility reaction and brain monoamine synthesis.

Female rats were given 16% ethanol solution as the sole liquid during the entire period of gestation. At birth the offspring was removed and reared by foster dams consuming normal tap water. The development of sensory motor behaviour and emotional reactions was delayed by 1-2 days in the prenatally ethanol exposed pups as assessed by tests on body righting, acoustic startle response, air righting, rearing and ultrasonic vocalization. In the open-field test the normally occurring behavioural difference between the sexes was not found in the prenatally ethanol exposed pups. Both sexes of the ethanol exposed pups behaved like the female controls suggesting deficient masculinization of the ethanol exposed male pups during foetal age. Biochemical analysis of the brains showed a decreased synthesis of serotonin and dopamine.

Amino Acids↗
PubMed1984

Development of sexual behavior in prenatally ethanol-exposed rats.

Female rats were given 16% ethanol solution as the sole liquid during the entire period of gestation. At birth the offspring was removed and reared by foster dams consuming normal drinking water. When tested for feminine sexual behavior in adulthood, the males showed marked signs of feminization as evidenced by an increased amount of lordosis responses. No changes were seen in the masculine sexual behavior. No deviations were seen in the female estrous cycles or in onset of vaginal estrus, whereas the onset of behavioral estrus was delayed. It is suggested that prenatal ethanol exposure may lower the fetal testosterone production and thereby interfere with the normal course of sexual differentiation in the male.

Animals↗