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Biomedical subjects

S O Ogren

Publications and source records attributed to S O Ogren.

At least 127 records · Page 7Linked to original sources
PubMed1987

Chronic imipramine treatment reduces (+)2-[125I]iodolysergic acid, diethylamide but not 125I-neuropeptide Y binding in layer IV of rat cerebral cortex.

The effects of chronic oral (2 X 10 mumol/kg, twice daily for 14 days) imipramine treatment on (+)2-[125I]-iodolysergic acid, diethylamide (125I-LSD) and 125I-neuropeptide Y (125I-NPY) receptor binding were examined in rat cerebral cortex by quantitative receptor autoradiography. A 35% reduction of 125I-LSD binding was observed in layer IV, both in the frontal and occipital cortex, while there was no significant change in 125I-NPY binding. The observed decrease in 125I-LSD binding is probably due to a reduction in the density of 5-hydroxytryptamine (5-HT) receptors of the 5-HT2 type. This reduction may represent a disturbance in the 5-HT synapses, regulating the transmission of the specific afferents innervating layer IV of the cerebral cortex.

Animals↗
PubMed1987

Effects of acute and chronic treatment with imipramine on 5-hydroxytryptamine nerve cell groups and on bulbospinal 5-hydroxytryptamine/substance P/thyrotropin releasing hormone immunoreactive neurons in the rat. A morphometric and microdensitometric analysis.

Groups of male rats were treated for a period of 14 days with imipramine (10 mumol/kg) given twice daily. Separate groups of rats received a single dose treatment using the same dose and experimental design as for the repeated treatment. Employing the avidin-biotin immunoperoxidase technique for immunohistochemistry 5-hydroxytryptamine (5-HT)-, substance P(SP)- and thyrotropin releasing hormone (TRH)-like immunoreactivities (IRs) were visualized in consecutive coronal sections of the brain stem and of the spinal cord. The IRs were studied by means of morphometric and microdensitometric procedures using automatic image analysis on profiles representing nerve terminal networks of the ventral horn of the cervical and lumbar enlargements of the spinal cord as well as their coexistence (5-HT/SP and 5-HT/TRH). With the same technique 5-HT IR was measured in the 5-HT nerve cell groups of the medulla oblongata (B1, B2, B3) and of the nucleus raphe dorsalis (B7) of the midbrain. In addition 5-HT and 5-hydroxyindolacetic acid (5-HIAA) levels were measured in the ventral and dorsal horns of the cervical and lumbar enlargements of the spinal cord using high performance liquid chromatography (HPLC). In the same parts of the spinal cord SP IR was studied by means of radioimmunoassay (RIA). The microdensitometric studies showed that chronic, but not acute, imipramine treatment selectively increased SP IR in the 5-HT/SP/TRH costoring nerve terminals of the medial part of the ventral horn in both the cervical and the lumbar enlargements. Furthermore, quantitative analysis of the entity of coexistence in the 5-HT nerve terminals networks of these areas showed that all the 5-HT nerve terminals contained SP and TRH IRs and that this phenomenon remained after acute and chronic imipramine treatment. The microdensitometric studies on the 5-HT nerve cell groups of the medulla oblongata and of the nucleus raphe dorsalis demonstrated that chronic, but not acute, imipramine treatment selectively increased 5-HT IR in the nerve cell bodies of the lateral part of group B3 as evaluated from the median grey values. Acute, but not chronic, imipramine treatment significantly increased the field area of 5-HT IR of nerve cell bodies in group B7, reflecting an increase in the mean profile area of the 5-HT IR nerve cell body profiles. Instead, the mean profile area of 5-HT IR cell bodies of group B1 was acutely reduced by imipramine.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Effects of subchronic treatment with imipramine, zimelidine and alaproclate on regional tissue levels of substance P- and neurokinin A/neurokinin B-like immunoreactivity in the brain and spinal cord of the rat.

The effects of subchronic (14 day) treatment with the inhibitors at the uptake of monoamines, zimelidine, alaproclate and imipramine, on regional levels of substance P (SP) and other tachykinins in tissue in the central nervous system of the rat were studied by radioimmunoassay. In the ventral spinal cord, in which substance P is known to exist together with 5-hydroxytryptamine (5-HT), in the terminals of descending neurones, treatment with the selective inhibitors of the uptake of 5-HT zimelidine (2 X 10 mumol/kg p.o.) or alaproclate (2 X 10 mumol/kg or 2 X 20 mumol/kg p.o.), increased the level of substance P-like immunoreactivity (SP-LI). The effect of alaproclate appeared to be dose-dependent. After treatment with imipramine (2 X 10 mumol/kg p.o.) only a tendency to increased levels of substance P-like immunoreactivity spinal cord was seen. Treatment with alaproclate, at the highest dose level, also elevated the concentration of neurokinin A/neurokinin B-like immunoreactivity (NKA/NKB-LI) in the ventral spinal cord. In the frontal cortex, in which separate monoaminergic and tachykinin-containing neurones interact, treatment with imipramine reduced the levels of SP-LI and NKA/NKB-LI, while treatment with alaproclate had the opposite effect. In the periaqueductal grey matter, treatment with zimelidine and alaproclate increased the levels of SP-LI and NKA/NKB-LI, while treatment with imipramine increased only the level of NKA/NKB-LI. In conclusion, subchronic treatment of rats with inhibitors of the uptake of monoamines induced changes in levels of tachykinin in frontal cortex, periaqueductal grey and spinal cord. The selective inhibitors of the uptake zimelidine and alaproclate, had similar effects on levels of tachykinin, while the inhibitor of the uptake of 5-HT and noradrenaline, imipramine induced changes in the frontal cortex, which were qualitatively different from the effects of zimelidine and alaproclate. Furthermore, the levels of different tachykinins were not always changed in parallel by the same treatment.

Alanine↗
PubMed1987

Evidence for a possible functional interaction between serotonergic and cholinergic mechanisms in memory retrieval.

A total of three experiments were conducted. In Experiment 1, the dose-dependent effects of the pretest administration of the serotonergic agonist alaproclate and the selective muscarinic cholinergic agonist oxotremorine, alone and in combination, were assessed in a one-trial inhibitory avoidance task. A clear dose-dependent enhancement of performance was demonstrated as a result of all three treatment conditions, which could not be explained in terms of nonspecific effects of the drugs on behavior in general. In addition, the facilitation of retrieval performance produced by the combined treatment of alaproclate and oxotremorine was observed at dose levels well below those observed following administration of either compound alone. In Experiment 2 attempts were made to block the enhancements of retention resulting from the different treatment conditions (alaproclate, oxotremorine, or the combination of alaproclate and oxotremorine) by pretreating the mice with either scopolamine (a muscarinic cholinergic antagonist) or quipazine (a serotonergic agonist). The results of these experiments indicate that (a) quipazine completely blocked the enhancement of retrieval resulting from alaproclate but not that following oxotremorine or oxotremorine in combination with alaproclate, while (b) scopolamine blocked the enhancement of retrieval resulting from oxotremorine alone as well as that resulting from alaproclate plus oxotremorine but failed to block the memory enhancement resulting from alaproclate. The present results lend further support to the view that both serotonin and acetylcholine play important roles in memory retrieval. More importantly, the results of the present series of experiments provide additional support for a functional interaction between the serotonergic and cholinergic nervous systems in the mediation of behavior.

Acetylcholine↗
PubMed1987

Differential effects of the dopamine antagonist remoxipride on apomorphine induced behaviour in the rat.

The effects of the novel substituted benzamide remoxipride on apomorphine induced behaviour in rats was investigated by means of an automatic holeboard apparatus. The ability of remoxipride to antagonise locomotion and gnawing induced by a high dose of apomorphine (5 mg/kg) and inhibition of exploration induced by a low dose of apomorphine (0.05 mg/kg) was tested. It was found that remoxipride in moderate doses potentiate locomotion and inhibit gnawing induced by the high dose of apomorphine while higher doses of remoxipride inhibits both apomorphine induced gnawing and locomotion. The inhibition of exploration following the low dose of apomorphine was not antagonised by remoxipride pretreatment. The results demonstrated that remoxipride has an interesting and unique profile of dopamine antagonistic effects in rat behavioural models.

Animals↗
PubMed1987

Investigation into the effects in-vitro of the 5-hydroxytryptamine reuptake inhibitor, alaproclate, on carbachol-stimulated inositol phospholipid breakdown in the rat cerebral cortex.

The effect of alaproclate in carbachol-stimulated inositol phospholipid (PI) breakdown in rat cerebral cortical miniprisms has been investigated. Carbachol-stimulated PI breakdown was greatly enhanced by increasing the assay potassium concentration from 5.88 to 18.2 mM. Alaproclate, on the other hand, did not influence carbachol-stimulated PI breakdown over the concentration range tested (0-100 microM) at either assay [K+]. The elution pattern of the inositol phosphates from the Dowex-1 columns was also unaffected by alaproclate both in the absence and presence of carbachol. Thus, the potentiation by alaproclate of tremor and salivation induced by the muscarinic agonist oxotremorine in-vivo reported previously is not seen when muscarinic function is measured in-vitro using carbachol-stimulated PI breakdown.

Alanine↗
PubMed1986

Central noradrenaline depletion attenuates amphetamine-induced locomotor behavior.

Male rats were given 6-hydroxydopamine-induced lesions of the locus coeruleus (LC) or the dorsal noradrenergic bundle (DNAB), prior to the measurement of locomotor and rearing activity induced by D-amphetamine. The increased locomotor activity induced by D-amphetamine (1.8 mg/kg) was significantly attenuated by both the LC and the DNAB lesions. The stimulatory effect of the 7.2 mg/kg dose of amphetamine was attenuated by the LC lesion, whereas the DNAB lesion potentiated this effect. The LC lesion also attenuated rearing induced by the 7.2 mg/kg dose of amphetamine. These results suggest some involvement of central noradrenergic neurons in the activity induced by amphetamine in the rat.

Animals↗
PubMed1986

The selective dopamine D2 receptor antagonist raclopride discriminates between dopamine-mediated motor functions.

The actions on central dopamine (DA) mechanisms of raclopride, a new substituted benzamide, were studied by means of behavioural and biochemical methods in the rat. Raclopride blocked the in vitro binding of the dopamine D2 antagonist 3H-spiperone (IC50 = 32 nM), but not of the unselective D1 antagonist 3H-flupenthixol (IC50 greater than 100,000 nM) in rat striatum, and failed to inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100,000 nM). Raclopride caused a dose-dependent increase in the DA metabolites HVA and DOPAC in the striatum and olfactory tubercle. Behavioural studies showed that raclopride discriminates between the motor behaviours induced by the DA agonist apomorphine. Thus, unlike haloperidol, raclopride blocked apomorphine-induced hyperactivity at considerably lower doses than those inhibiting oral stereotypies. Moreover, raclopride showed a high separation between the doses for blockade of apomorphine-induced hyperactivity and those inducing catalepsy in rats. Raclopride caused a dose-dependent blockade of the specific binding of 3H-spiperone and 3H-N-n-propylnorapomorphine (3H-NPA) in vivo at doses similar to those blocking the behavioural effects of apomorphine. The maximal blockade of 3H-spiperone binding in vivo was lower for raclopride than for haloperidol. Raclopride caused a greater inhibition of 3H-NPA than of 3H-spiperone in vivo binding in the striatum. It is suggested that the ability of raclopride to discriminate between different DA-mediated functions may be attributed to a preferential blockade of a subclass of functionally coupled dopamine D2 receptors in striatal as well as in extrastriatal brain regions in the rat.

Adenylyl Cyclases↗
PubMed1986

Serotonin type-2 receptor mediated regulation of substance P release in the ventral spinal cord and the effects of chronic antidepressant treatment.

Regulation of the release of substance P (SP) by the coexisting neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in the ventral spinal cord and the effects of chronic antidepressant treatment mediated changes in serotonin metabolism on the regulation, were examined. The K+ (40 mmol/l) evoked release of (SP) from slices of the ventral spinal cord of the rat was potentiated by (5-HT) applied to 100 mumol/l concentration. This effect was blocked by the serotoninergic antagonists methysergide (10 mumol/l), methiotepin (10 mumol/l) and fully blocked by ketanserin (10 mumol/l). Thus the 5-HT receptor which regulates the release of SP appears to belong to the type-2 5-HT receptors. Chronic treatment with the selective serotonin uptake inhibitor zimelidine (14 days, 2 X 10 mumol/kg/day, p.o.) lowered the tissue levels of the 5-HT metabolite: 5-hydroxyindol acetic acid (5-HIAA) and elevated the tissue levels of SP in both the ventral and dorsal spinal cord as compared to that in the vehicle treated group (14 days, 2 X 5 ml saline/kg/day, p.o.). The decrease in the 5-HIAA levels after chronic zimelidine treatment was quantitatively similar in the dorsal (33%, p less than 0.01) and ventral (31%, p less than 0.05) spinal cord. The increase in SP levels after chronic zimelidine treatment was more pronounced in the ventral cord (80%, p less than 0.01) where the majority of the SP containing nerve endings also contain 5-HT, than in the dorsal spinal cord (22% increase in SP, p less than 0.05), where only a minor fraction of the SP-containing nerve endings shows a 5-HT/SP coexistence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Dopamine D2 receptors and dopamine metabolism. Relationship between biochemical and behavioural effects of substituted benzamide drugs.

The effect of the substituted benzamide dopamine D2 receptor antagonists sulpiride, raclopride, FLA 966(-), FLA 988(-), eticlopride and remoxipride as well as the "classical" dopamine antagonists, haloperidol and chlorpromazine, on the concentrations of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain of the rat was investigated. All compounds increased the turnover of dopamine, as defined by increased concentrations of DOPAC and HVA (without change in the concentration of dopamine) in the striatum in a dose-dependent manner. The doses of the compounds producing increased turnover of dopamine in the striatum were in the same range as those displacing the in vivo binding of [3H]spiperone in the striatum. In addition, for all the compounds tested in the study, an increase in the turnover of dopamine to about 300% of control was observed for doses antagonising the stereotypy produced by the dopamine agonist, apomorphine. On the other hand, no consistent relationship between increased turnover of dopamine and the doses of the compounds required to antagonise apomorphine-induced hyperactivity was found. This result was also found in limbic areas. Remoxipride and haloperidol had little or no effect on the turnover of dopamine in either the hypothalamus or substantia nigra at the ED50 doses of these compounds for antagonism of apomorphine-induced stereotypy.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Conditioned taste aversion to ethanol induced by zimeldine.

Conditioned taste aversions (CTA) were induced to both ethanol and saccharin solutions with the serotonin uptake inhibitor Zimeldine. When animals were pretreated with Zimeldine prior to the presentation of a novel flavour a CTA did not result. However, there is evidence that Zimeldine induces an unconditioned suppression of drinking. These results are discussed in terms of their relevance to Zimeldine's effects on voluntary ethanol consumption.

5-Hydroxytryptophan↗
PubMed1986

Analysis of the avoidance learning deficit induced by the serotonin releasing compound p-chloroamphetamine.

The effects of the serotonin-releasing compound p-chloroamphetamine (PCA, 2.5 mg/kg) on avoidance acquisition, retention and memory retrieval were examined in male Sprague-Dawley rats using a one-way active avoidance and a one-trial passive avoidance task. The drug was injected IP prior to training, following acquisition and prior to the retention test 24 hr after training using a state-dependent design. In the normal context situation pretraining administration of PCA markedly impaired active avoidance acquisition, but PCA-treated rats did not differ from controls in their retention performance when tested 24 hr after training. In the dark/light box test pretraining administration of PCA caused a dose-dependent impairment of both active and passive avoidance retention which could not be explained in terms of changes in locomotor activity or behavioural disinhibition at the time of testing or state-dependent retention. Post-training administration of PCA failed to affect avoidance retention in both tasks. The drug was found to impair memory retrieval in a dose- and time-dependent fashion in the one-way active but not in the passive avoidance test. Pretraining administration of PCA produced a progressive loss of passive and active avoidance performance at increasingly longer retention intervals. The present results suggest that serotonin has dual effects on processes underlying learning and memory involving effects on both associative and non-associative learning processes in the rat. The time-dependent loss of memory retention following 5-HT release indicates that serotonin has a role in the way information is processed in the brain.

Amphetamines↗
PubMed1986

Potential neuroleptic agents. 4. Chemistry, behavioral pharmacology, and inhibition of [3H]spiperone binding of 3,5-disubstituted N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamides.

A series of 3,5-disubstituted N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxysalicylamides was synthesized, starting from the 2,6-dimethoxybenzoic acids, by boron tribromide demethylation of the corresponding 3,5-disubstituted 2,6-dimethoxybenzamides and separation of the two positional isomers. The correct structure assignments were based on selective decoupling studies on their 13C NMR spectra. The salicylamide derivatives were tested for antidopamine activity in vivo by their ability to inhibit the apomorphine syndrome in the rat and in vitro by their ability to displace [3H]spiperone from striatal preparations of the rat brain. The activity seems to reside exclusively in the S enantiomer. Several compounds were considerably more potent than haloperidol, particularly those having an ethyl group in the 3-position and a halogen atom in the 5-position of the aromatic ring. The corresponding 5-alkyl-3-halogen-substituted compounds were much less active. A low acute toxicity was found for the most potent compounds. Some of the salicylamides displayed a 10-20-fold separation between the dose which blocks apomorphine-induced hyperactivity and that which blocks apomorphine-induced stereotypy. One compound, S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxysalicylamide (raclopride, FLA 870) (13) had a stereotypy--hyperactivity separation more than twice that of sulpiride while being 100 times more potent in blocking the apomorphine effects. On this basis, 13 was selected for clinical trials against schizophrenia.

Animals↗
PubMed1986

Serotonin receptor involvement in the avoidance learning deficit caused by p-chloroamphetamine-induced serotonin release.

The receptor involvement in the p-chloramphetamine (PCA, 2.5 mg kg-1) induced impairment of active avoidance acquisition was examined in the male rat. The avoidance deficit was blocked at low doses by serotonergic (5-HT)-receptor blocking agents but not by alpha-adrenergic-, beta-adrenergic-, opiate-, muscarinic- or dopamine D2-receptor antagonists. The potency of the 5-HT antagonists to block the PCA-induced deficit correlated with their affinity in displacing [3H]ketanserin but not [3H]5-HT binding in the frontal cortex. The potencies of the 5-HT antagonists to block the action of PCA could not be related to their action on muscarinic-, histaminergic H1- or dopaminergic D2-receptor binding in vitro. It is concluded that the avoidance learning deficit caused by PCA-induced 5-HT release is related to activation of 5-HT receptors in the frontal cortex having the characteristics of a 5-HT2 receptor.

Adrenergic alpha-Agonists↗
PubMed1986

Chlormethiazole--mode of action.

Studies in mice demonstrated that the anticonvulsant profile of chlormethiazole differs from that of diazepam and the barbiturates. Chlormethiazole protects animals from convulsions induced by a wide variety of chemoconvulsants known to block the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), such as bicuculline, picrotoxin, isoniazid and pentetrazol, thus confirming and extending earlier studies on its broad anticonvulsant characteristics. Chlormethiazole is particularly potent against isoniazid-induced convulsions, which are probably induced by reductions of GABA levels in the brain. Chlormethiazole was found to have a weak action on benzodiazepine receptor binding, GABA receptor binding and kainic acid receptor binding. Chlormethiazole inhibited picrotoxin binding at very high concentrations, but lowered the functional effects of picrotoxin at much lower concentrations than those affecting picrotoxin binding. Moreover, chlormethiazole failed to change GABA or glutamate levels in the brain and did not affect glutamic acid decarboxylase (GAD) activities in the rat brain. Muscimol (a GABAA agonist) enhanced the anticonvulsant activity of chlormethiazole against picrotoxin but not against bicuculline-induced convulsions. Muscimol enhanced the anticonvulsant potency of diazepam against both chemoconvulsants. These data suggest that the anticonvulsant activity of chlormethiazole is not mediated directly through changes in GABA or glutamate levels or by a direct (agonist) action at the GABA or benzodiazepine receptor complex. These findings suggest that chlormethiazole may enhance GABA transmission beyond the GABA receptors, hypothetically at the level of the GABA receptor coupled ionophore (e.g. the chloride ion channel). Applied micro-iontophoretically, chlormethiazole was found to potentiate the inhibitory responses to GABA, muscimol and glycine, but not to acetylcholine. The potentiation of glycine-mediated inhibition is unique for chlormethiazole and does not occur with any other known anticonvulsant (barbiturates, benzodiazepine, phenytoin or sodium valproate). Studies in primary cultures, derived from spinal cord neurones, showed that chlormethiazole produces hyperpolarization together with an increase in the threshold for action potential generation. Further in vitro studies indicated that chlormethiazole acts on some types of Ca2+-dependent chloride ion channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Forebrain serotonergic involvement in avoidance learning.

The one-way active avoidance deficit caused by the serotonergic (5-HT) releasing compound p-chloroamphetamine (PCA) was examined in rats after degeneration of 5-HT neurons in the forebrain. Injection of 5,7-dihydroxytryptamine (5,7-DHT) into the forebrain in desipramine (20 mg/kg)-pretreated rats resulted in a 65-70% decrease in 5-HT concentrations in the prefrontal cortex and hippocampus without any significant effect on striatal 5-HT. Slight reductions in noradrenaline (NA) (25%) and dopamine (DA) (34%) concentrations were observed in the prefrontal cortex only. The 5,7-DHT lesions markedly attenuated the impaired avoidance performance induced by PCA (2.5 mg/kg), suggesting that the avoidance deficit depends on intact 5-HT terminals in cortex and/or hippocampus. The 5,7-DHT lesion alone caused a slight but significant impairment of acquisition. The results suggest that 5-HT terminal systems in the forebrain play an important role in avoidance learning.

5,7-Dihydroxytryptamine↗