Biomedical subjects

S Liljequist

Publications and source records attributed to S Liljequist.

At least 55 records · Page 3Linked to original sources

PubMed1991

Modulation of protein kinase C translocation by excitatory and inhibitory amino acids in primary cultures of neurons.

In primary cultures of neurons from rat cerebral cortex and neostriatum, excitatory amino acids stimulate the translocation of protein kinase C (PKC) from the cytoplasm to the membrane. In the presence of a physiological concentration of Mg2+ in the extracellular medium, glutamate induces PKC translocation by binding to both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) excitatory amino acid receptors. Quisqualate translocates the enzyme by stimulating primarily AMPA receptors and possibly metabotropic receptors. NMDA receptor-induced PKC translocation is sodium independent, whereas quisqualate receptor-induced PKC translocation is sodium dependent; none of the agonists is active in the absence of calcium from the extracellular medium. Muscimol does not modify excitatory amino acid stimulation; however, blockade of gamma-aminobutyric acid(A) receptors by bicuculline greatly enhances glutamate-induced PKC translocation. This enhancement is blocked by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) and by tetrodotoxin.

Amino Acids↗

PubMed1990

Environment-dependent effects of ethanol on DOPAC and HVA in various brain regions of ethanol-tolerant rats.

The development of tolerance to the behavioral and biochemical effects of ethanol was studied. Rats were made tolerant to ethanol by the administration of daily ethanol injections (3 g/kg, IP) for 7 and 28 days. Tolerance developed both to the behavioral (hypothermic, sedative) and biochemical (accumulation of dopamine metabolites in various brain areas) actions of ethanol. However, it was found that this tolerance to both the behavioral and biochemical effects of ethanol was no longer present when previously ethanol-tolerant animals were moved from their home environment and given a challenge dose of ethanol (2.5 g/kg; IP) in a new, unfamiliar environment. Our findings confirm that ethanol tolerance cannot be explained on the basis of a singular neurochemical event. The development of ethanol tolerance is due to a complex interaction between environmental, learning, and biochemical factors.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

Effects of amperozide in two animal models of anxiety.

The novel psychotropic agent amperozide (amp) was investigated in two different rat anxiety models, Vogel's conflict test (VT) and Montgomery's conflict test (MT). In the VT, amp in lower doses (0.2-0.6 mg/kg subcutaneously) increased the number of shocks accepted, as compared to controls. Pretreatment with the specific benzodiazepine receptor antagonist Ro 15-1788 (10.0 mg/kg orally) or the GABA-A receptor antagonist bicuculline (2.0 mg/kg intraperitoneally) antagonized the anticonflict effect of amp (0.4 mg/kg subcutaneously). At the highest dose tried (2.0 mg/kg subcutaneously) amp instead decreased the number of shocks accepted. Both 0.4 mg/kg and 2.0 mg/kg of amp raised the shock threshold, as compared to controls. The latter dose also decreased the motivation to drink. Pretreatment with Ro 15-1788 (10.0 mg/kg orally) did not significantly change the shock threshold or the drinking motivation, as compared to the group receiving amp alone. In the MT, amp (0.05-0.1 mg/kg subcutaneously) increased the percentage time spent in the open arms, while no changes were seen in the number of entries made into these arms. After higher doses (0.4-0.8 mg/kg subcutaneously) no differences, as compared to controls, were observed. Amp (1 nM-10microM) exhibited no affinity for 3H-flunitrazepam binding sites in mouse forebrain membranes in vitro. Taken together, the present data suggest that amp in low doses produces anticonflict (anxiolytic-like) effects. These effects appear to be mediated through an indirect (via 5-HT and/or DA systems?) activation of the GABA/benzodiazepine chloride ionophore receptor complex.

Animals↗

PubMed1989

The effect of ethanol on 35S-TBPS binding to mouse brain membranes in the presence of chloride.

The effect of in vitro and in vivo administration of ethanol on the binding of 35S-t-butyl-bicyclophosphorothionate (35S-TBPS) to cortical brain membranes of C57Bl mice was investigated using KCl (100 mM) containing assay media. The in vitro addition of ethanol produced a dose-dependent inhibition of basal 35S-TBPS binding. In the presence of chloride ions, GABA and pentobarbital had a biphasic action (stimulation followed by inhibition) on 35S-TBPS binding, whereas diazepam only stimulated the binding. Ethanol reduced the stimulatory effects of GABA and pentobarbital in a dose-dependent manner, but had no effect on the enhancement of 35S-TBPS binding produced by diazepam. 35S-TBPS binding to cortical brain membranes was inhibited by the putative Cl- channel blocking agent DIDS. This inhibitory action of DIDS was significantly, and dose-dependently reduced by ethanol (greater than or equal to 100 mM ethanol). Chronic ethanol ingestion in vivo, which produced tolerance to and physical dependence on ethanol in the animals, did not alter the stimulatory and inhibitory effects of GABA and pentobarbital on 35S-TBPS binding. The enhancement of 35S-TBPS binding produced by diazepam was slightly, but significantly, enhanced in brain membranes from animals which had undergone 24 hours of ethanol withdrawal. Chronic ethanol treatment did not change the potency of picrotoxin and of the peripheral BDZ-receptor ligand RO 5-4864 to competitively inhibit 35S-TBPS binding. Our results suggest that in vitro addition of ethanol alters the activity of the GABA/benzodiazepine (BDZ) receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1987

Effects of ethanol on the activity of brain enzymes.

Ethanol alters, in a selective manner, the activity of several membrane-bound enzymes in the central nervous system (CNS) which are important for neuronal transmission of information. Ethanol inhibits Na+/K+-transporting ATPase activity, while adenylate cyclase (AC) activity is stimulated by ethanol added in vitro. Ethanol's effects on AC activity are mediated primarily via effects on proteins that regulate AC activity. Ethanol has selective effects on monoamine oxidase activity, in that the B form of the enzyme is more sensitive to inhibition by ethanol added in vitro. The selective effects of ethanol on different membrane-bound CNS enzymes may result from differing membrane lipid microenvironments of the enzymes, or from differences in the enzyme proteins per se.

Adenylyl Cyclases↗

PubMed1987

Ethanol-induced modulation of 35S-TBPS binding to brain membranes.

The effect of ethanol in vitro on the binding of 35S-t-butylbicyclophosphorothionate to brain membranes was examined. Ethanol inhibited basal binding of 35S-TBPS both in potassium bromide- (KBr)- and potassium chloride (KCl)-containing assay media. Ethanol was, however, considerably weaker in reducing 35S-TBPS binding in buffers with 100 mM KCl. Ethanol had no effect on the inhibition of 35S-TBPS binding produced by GABA and pentobarbital in the presence of KBr or KCl, whereas it clearly altered the enhancement of 35S-TBPS binding produced by these drugs when the assay was carried out in buffers containing KCl.

Animals↗

PubMed1986

Bicuculline-pentobarbital interactions on [35S]TBPS binding in various brain areas.

The effect of in vitro addition of pentobarbital to brain membrane preparations from cerebellum and cortex of C57B1 mice was examined in the presence and absence of the specific GABAA receptor "antagonist" bicuculline. In the cortex pentobarbital produced a biphasic effect (stimulation followed by inhibition) on [35S]TBPS binding, whereas only inhibition of [35S]TBPS binding was observed in the cerebellum. When bicuculline was added to assay mixtures, the stimulatory action of pentobarbital was markedly enhanced in the cortex. In the cerebellum the presence of bicuculline uncovered a biphasic effect of pentobarbital on [35S]TBPS binding, that is lower doses of pentobarbital increased, while higher doses decreased [35S]TBPS to the membrane receptors from the cerebellum.

Animals↗

PubMed1986

Effect of ethanol on the binding of 35S-T-butylbicyclophosphorothionate to mouse brain membranes.

The effect of in vitro addition of ethanol (0.02-1.0 M) on the binding of 35S-TBPS was examined in brain membranes from cerebellum and cortex of naive or chronically ethanol-treated C57B1 mice. In brain membranes of untreated animals, increasing concentrations of ethanol produced a dose-related inhibition of 35S-TBPS binding in the brain areas investigated. Additional studies showed that this effect of ethanol was due to a decreased affinity of 35S-TBPS for its binding sites. Chronic treatment of the animals with ethanol, which produced tolerance to and dependence on ethanol, did not alter ethanol's ability to inhibit the binding of 35S-TBPS. In naive animals, the in vitro addition of GABA or pentobarbital produced a pronounced inhibition of 35S-TBPS, both drugs being more potent in the cerebellum than in the cortex. Picrotoxin also produced a dose-dependent inhibition at 35S-TBPS, but was equally potent in the brain areas investigated. The inhibition by GABA or pentobarbital was not influenced by in vitro addition of a physiologically relevant concentration of ethanol (100 mM), whereas ethanol produced a significant increase in the IC50 values for picrotoxin both in the cortex and in the cerebellum. Furthermore, the inhibitory effects of GABA or pentobarbital on 35S-TBPS binding remained unchanged in animals chronically treated with ethanol for 7 days. Our data indicate that ethanol may affect the GABA receptor system through a rather specific interaction with the 35S-TBPS recognition site, but that this action of ethanol is not altered by the development of tolerance to and dependence on ethanol.

Animals↗

PubMed1986

Activation of alpha 2-adrenoreceptors enhances haloperidol-induced suppression of operant behavior.

Inhibition of catecholamine synthesis by alpha-methyl paratyrosine (alpha-MT) was previously shown to potentiate the behavioral suppression caused by dopamine-receptor antagonists. This effect of alpha-MT is in all probability due to inhibition of the compensatory increase in dopamine turnover induced by the dopamine receptor antagonists. In the present study we investigated the effect of the alpha 2-adrenoreceptor agonist clonidine on the haloperidol-induced suppression of food-reinforced lever-pressing behavior (fixed ratio 40:1) in rats. Small behaviorally inactive doses of clonidine were found, in analogy with alpha-MT, to enhance the haloperidol-induced suppression of the lever-pressing behavior. The haloperidol-induced increase in dopamine synthesis (measured as the accumulation of DOPA after inhibition of aromatic amino acid decarboxylate) was antagonized by clonidine in the striatum as well as in the dopamine rich limbic regions. Prazosin, a selective alpha 1-adrenoreceptor antagonist had no effect on the clonidine induced behavioral changes. Idazoxane, a selective alpha 2-adrenoreceptor antagonist, counteracted both the behavioral and biochemical effects of clonidine, indicating that these effects of clonidine are mediated via its action on alpha 2-adrenoreceptors. The present findings provide support for the notion that alpha 2-adrenoreceptors may participate in the regulation of nigro-striatal as well as meso-limbic dopaminergic activity. It is suggested that alpha 2-adrenoreceptor agents, especially in combination with classical antipsychotics, might be of therapeutic value in the treatment of disorders associated with abnormal dopaminergic activity.

Animals↗

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

Anticonflict effect of the putative serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).

The putative 5-HT agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) produced in rats an increase in the number of shocks accepted in a modified Vogel's conflict test design. Subchronic pretreatment with p-chlorophenylalanine (PCPA) similarly caused release of the punished behavior. This anticonflict effect of PCPA was antagonized by both 5-hydrotryptophan and 8-OH-DPAT. Thus in naive animals 8-OH-DPAT exerting anticonflict effects acted like a 5-HT antagonist, whereas in subchronically PCPA-pretreated animals with presumably supersensitive 5-HT receptors, 8-OH-DPAT decreasing the number of accepted shocks acted like a 5-HT agonist.

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

PubMed1984

Specific effects of chronic phenobarbital administration on high- and low-affinity benzodiazepine receptors in mouse cerebellum and forebrain.

Characteristics of [3H]flunitrazepam ([3H]FLU) binding to cortical and cerebellar membrane receptors were examined following chronic (six days) administration of phenobarbital (PB) to C57B1 mice. Following PB treatment, the number of [3H]FLU binding sites (Bmax) was significantly reduced in both cerebral cortex and in cerebellum. No change in the affinity (KD) of these binding sites was observed. Using 3-methyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazolo [4,3-beta]pyridazine (CL-218,872), further analysis revealed a significant decrease in the number of high-affinity CL-218,872 binding sites in cerebellar tissue. In the forebrain areas, however, a significant decrease in the number of low-affinity binding sites was found. Finally, the enhancement of [3H]FLU binding, produced by in vitro addition of pentobarbital, was significantly less pronounced in the cerebellum of PB-treated animals.

Animals↗

PubMed1984

Reversal of the anti-conflict action of valproate by various GABA and benzodiazepine antagonists.

The effects of RO 15-1788, RO 5-3663, picrotoxin and bicuculline on the anti-conflict properties of valproate were studied in rats using a modified Vogel 's conflict test procedure. A low dose of the benzodiazepine (BDZ) antagonist, RO 15-1788 (5 mg/kg), blocked the anti-punishment properties of valproate (400 mg/kg), whereas no antagonism was observed after a high dose (25 mg/kg) of the BDZ antagonist. High doses of RO 5-3663 or picrotoxin also reversed the anti-conflict action of valproate. Bicuculline did not change the effects of valproate in this test situation. The suppressive effect of valproate on locomotor activity was reversed by a low dose (5 mg/kg) of RO 15-1788, but not by the other antagonists. RO 5-3663 was the only antagonist which effectively reversed the muscle relaxant effects of valproate observed in a Rotarod performance test. These findings indicate that various pharmacological actions of valproate may be due to a complex interplay with several sites at the GABA-BDZ-receptor complex.

Animals↗

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↗

PubMed1984

The effects of GABA and benzodiazepine receptor antagonists on the anti-conflict actions of diazepam or ethanol.

The effects of picrotoxin, bicuculline or RO 15-1788 on the anti-conflict action(s) of diazepam or ethanol were studied in rats using a modified Vogel's conflict test procedure. RO 15-1788 antagonized the anti-punishment effects of diazepam (2.5 mg/kg, IP), whereas various doses of bicuculline or picrotoxin did not interfere with diazepam's anti-conflict effect in this test situation. The anti-conflict action of ethanol (2 g/kg, IP) was antagonized by picrotoxin (1.0 mg/kg, IP), whereas both bicuculline and RO 15-1788 were without effect on the increased punishment response produced by ethanol. These data suggest that the anti-conflict properties of ethanol are at least partially mediated through an enhancement of central GABAergic activity.

Animals↗

PubMed1983

Differential effects of insulin on brain monoamine metabolism in rats.

The effect of a subconvulsive dose of insulin, which caused a 70% reduction of plasma glucose levels, on catecholamine and 5-hydroxytryptamine turnover in different brain regions of rats was investigated. The turnover of norepinephrine was found to be increased in the hemispheres and that of 5-hydroxytryptamine was increased in the limbic forebrain and hemispheres, whereas the dopamine turnover was decreased in the striatum and limbic forebrain.

5-Hydroxytryptophan↗

PubMed1982

Effects of GABAergic agonists and antagonists on various ethanol-induced behavioral changes.

The interaction between ethanol and various GABAergic drugs (muscimol, bicuculline, picrotoxin) with regard to their effects on locomotor activity, drug-induced sleep, body temperature, and convulsions was studied. It was demonstrated that the GABA receptor agonist muscimol potentiated the sedative properties of ethanol, while the opposite effect, a reduction of ethanol-produced sedation, was seen upon administration of the GABA receptor blocking agent picrotoxin. Consequently, the results from the present series of experiments indicate that ethanol enhances central GABAergic activity.

Animals↗