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Biomedical subjects

S O Ogren

Publications and source records attributed to S O Ogren.

At least 163 records · Page 9Linked to original sources
PubMed1984

Effects of antidepressant drugs on histamine-H1 receptors in the brain.

The histamine-H1 receptor blocking properties of a number of structurally different antidepressant drugs have been evaluated using a 3H-mepyramine binding assay and a guinea-pig ileum preparation. The tricyclic antidepressants all inhibited the histamine-H1 receptor. Some newer antidepressant drugs, such as zimelidine and nomifensine were devoid of activity while others, such as iprindole and mianserin were very potent. It is concluded that antagonistic effects on the histamine-H1 receptor is not associated with the therapeutic efficacy in depression, but may contribute to the sedative effects of the antidepressant drugs.

Animals↗
PubMed1984

Selective lesions of the bulbospinal serotonergic pathways reduce the analgesia induced by p-chloroamphetamine in the hot-plate test.

The antinociceptive effect of the serotonin releasing compound p-chloroamphetamine (PCA) was investigated in rats by means of the hot-plate method. Selective neurotoxic lesions of the descending serotonergic pathways induced by intrathecal injections of 5,6-dihydroxytryptamine (20 micrograms, 7 days before testing), produced hyperalgesia and significantly attenuated the analgesic effect of acutely administered PCA (2.5 mg/kg). The lesions reduced the spinal serotonin content by about 90% without significantly altering noradrenaline levels. It is concluded that the descending serotonergic pathways contribute to the expression of PCA-induced hot-plate analgesia.

5,6-Dihydroxytryptamine↗
PubMed1984

Retention deficits induced by acute p-chloroamphetamine following fear conditioning in the rat.

Rats were given four inescapable shocks (1.0 mA) when confined to the right-hand corner of a modified shuttlebox. p-Chloroamphetamine (PCA) injected just before the retention test 24 h later completely blocked the immobile posture that was observed after saline injections. This retention deficit was shown to be selectively associated with 5-hydroxytryptamine (5-HT) release, since the administration of the 5-HT uptake inhibitors zimelidine and citalopram 60 min prior to PCA antagonized this effect. The 5-HT specificity of the deficit was further established by the findings that 5-HT-depleted rats (PCA, 2 x 10 mg/kg, and fenfluramine, 2 x 25 mg/kg), but not NA-depleted rats (DSP4, 1 x 50 mg/kg), or rats treated with zimelidine (2 x 20 mg/kg) 60 min before PCA (2 x 10 mg/kg), showed an almost complete blockade of the retention failure. The data presented may provide a useful experimental model for investigating the efficacy of functional 5-HT activity in the treatment of phobic anxiety.

Amphetamines↗
PubMed1984

Decreased morphine intake by opiate addicted rats administered zimelidine, a 5-HT uptake inhibitor.

Zimelidine, a specific 5-HT uptake inhibitor, reduced peroral morphine consumption by morphine-addicted adult male and female Sprague-Dawley rats and old male rats in choice tests. The effect was dose dependent in male rats. Thus, the availability of central 5-HT appears to be important for the regulation of morphine preference in rat. The results are discussed in relation to recent literature where ethanol preference has been found to be attenuated by zimelidine. The results may provide insights into the complex cellular mechanisms underlying opiate addiction.

Animals↗
PubMed1984

The effect of acute zimeldine and alaproclate administration on the acquisition of two-way active avoidance: comparison with other antidepressant agents, test of selectivity and sub-chronic studies.

The dose-dependent effect of acute zimeldine and alaproclate treatment upon the acquisition of two-way and one-way active avoidance in the rat was studied in a single-session and in a repeated-sessions design. Zimeldine (5-20 mg/kg, IP), but not alaproclate, caused disruptions of two-way avoidance acquisition. Acquisition deficits were also caused by citalopram and fluoxetine but not the other antidepressant drugs tested. Zimeldine, but not alaproclate or desipramine, caused a slight but non-significant impairment of one-way active avoidance; neither zimeldine nor alaproclate produced any effects upon fear conditioning and retention testing. The long-term action of p-chloroamphetamine (2 X 10 mg/kg) antagonised the acute zimeldine effect totally, and chronic treatment with zimeldine (15 days, 1 X 50 mumol/kg) and chlorimipramine (15 days, 2 X 10 mumol/kg) also caused some partial blockade of the two-way avoidance deficit. These data seem to suggest some involvement of serotonin (5-HT) in the observed disruptions of two-way active avoidance caused by acute zimeldine treatment.

Alanine↗
PubMed1984

Role of serotonin in memory: facilitation by alaproclate and zimeldine.

The effects of alaproclate and zimeldine on memory retrieval were examined in male Swiss-Webster mice using a one-trial inhibitory avoidance task. All drugs were administered IP prior to the retention test 24 h after training. Both drugs were found to facilitate memory retrieval significantly in a dose- and time-dependent fashion that could not be explained in terms of non-specific effects of the drug (illness, lack of motility, etc.) at the time of the test. The temporal effects of alaproclate and zimeldine on memory closely followed their course of concentration of the drug within the blood stream. The facilitation of retrieval induced by alaproclate and zimeldine was blocked by the putative serotonergic receptor agonist quipazine but not blocked by the antagonist cyproheptadine. Pretreatment with quipazine alone in a group of animals trained to a shock level which normally results in high levels of suppression was not sufficient to produce memory impairment, suggesting that quipazine was probably antagonizing the facilitative effects of alaproclate and zimeldine directly, rather than overriding the facilitation through an indirect action on retrieval in general. The present results lend further support to the suggestion that serotonin plays a significant role in memory.

Alanine↗
PubMed1984

Alaproclate, a new selective 5-HT uptake inhibitor with therapeutic potential in depression and senile dementia.

Alaproclate, a new specific 5-HT uptake inhibitor, was examined for its action on several receptors in the brain, for its action on the NA, DA and 5-HT uptake mechanisms in vivo and for its action on brain biogenic amine content. Alaproclate was practically devoid of action on a number of receptors as examined in binding studies in vitro: 5-HT, histamine-H1, alpha 1, -alpha 2-adrenergic and dopamine D2 receptors. Alaproclate had also a weak affinity for 3H-norzimeldine binding sites in contrast to imipramine. Unlike the tricyclic antidepressants alaproclate had a negligible action on muscarinic receptors and failed to block muscarinic induced stimulation in vivo. Contrary to clomipramine alaproclate failed to block NA uptake in vivo. Alaproclate was found to display a regional selectivity in blocking 5-HT uptake in vivo (measured with the H 75/12-method). The compound was most potent in the hippocampus and hypothalamus followed by striatum and cerebral cortex with a low potency in the spinal cord. The results are discussed in relation to a previously presented carrier site model for serotonin reuptake.

Alanine↗
PubMed1984

Test-dependent variations in the antinociceptive effect of p-chloroamphetamine-induced release of 5-hydroxytryptamine.

p-Chloroamphetamine (PCA), in doses that did not significantly impair motor performance in a rotating-wheel task, induced marked analgesia in rats tested with the hot-plate and flinch-jump methods. In the tail-flick test, moderate hyper- or hypo-analgesia was found to be dependent on dose. In hot-plate experiments the analgesia was attenuated by inhibition of uptake of 5-HT (with zimelidine), depletion of stores of 5-HT (with PCPA) and by lesioning of 5-HT-containing terminals (long-term PCA treatment). Blockade of serotonin receptors by metergoline produced hyperalgesia, but failed to reduce the analgesia induced by p-chloroamphetamine. Manipulation of catecholaminergic and opioid systems did not reduce the effect of p-chloramphetamine. It is concluded that induction of release of 5-HT by chloroamphetamine induces antinociception which varies in magnitude between tests, suggesting that different serotonergic mechanisms modulate complex and reflex responses to noxious stimulation. The failure of metergoline to antagonize the analgesia induced by p-chloroamphetamine suggests an involvement of 5-HT receptors different from the ones implicated in other types of behaviour mediated by 5-HT.

Amphetamines↗
PubMed1984

Selective depletion of norepinephrine in brain by N-2-chloroethyl-N-ethyl-2-bromobenzylamine fails to alter the voluntary consumption of ethanol in rats.

The effects of the selective norepinephrine neurotoxin, DSP-4, on the maintenance of voluntary consumption of ethanol was tested in male Long-Evans rats. The drug, DSP-4, produced a 51% reduction in whole brain levels of NE without affecting the consumption of ethanol. These results, however, do not rule out a role for NE in mediating this behavior.

Alcohol Drinking↗
PubMed1984

Limited involvement of central noradrenergic pathways in morphine-induced antinociception.

Lesioning of cerebral and spinal noradrenergic terminals by the neurotoxin DSP4 (50 mg/kg, 7 days prior to testing) significantly attenuated the effect of morphine (2.5-7.5 mg/kg) in rats tested with the hot-plate test. The effect of DSP4 was prevented by pretreatment with the selective inhibitor of uptake of NA, desipramine. Treatment with DSP4 did not attenuate the effect of morphine (5 mg/kg) in the flinch-jump and tail-flick tests, and did not by itself change the nociceptive thresholds in any of the tests. It is concluded that noradrenergic structures in the central nervous system play a limited role in analgesia induced by morphine.

Animals↗
PubMed1984

Zimeldine: a review of its effects on ethanol consumption.

This review evaluates the literature and describes an extensive series of experiments which examined the effects of zimeldine , its metabolite norzimeldine and other serotonin and norepinephrine reuptake inhibitors on voluntary ethanol consumption in rats. The results of these experiments indicate that drugs which specifically inhibit serotonin reuptake are capable of decreasing voluntary ethanol consumption. The behavioral mechanism through which these drugs exert their effects seems to be extinction of the primary reinforcing properties of alcohol. These effects seem to be partially attenuated both by drugs which modulate the norepinephrine system as well as by the serotonin postsynaptic receptor blocker methergoline. The data presented in this review are discussed in terms of the involvement of the serotonin and norepinephrine systems in the mechanism of action of these drugs. In addition, several alternative hypotheses concerning the nature of the phenomenon are offered. Finally, the implications of these data for the possible development of a treatment procedure for problem drinkers is discussed.

Alcohol Drinking↗
PubMed1984

Studies on the mechanism of action of substituted benzamide drugs.

The effects of classical neuroleptic drugs (haloperidol, chlorpromazine) and atypical neuroleptics, i.e. substituted benzamides (L-sulpiride, tiapride, FLA 731(-] on specific in vivo binding of the dopamine antagonist 3H-spiperone and the dopamine agonist 3H-n-propylnorapomorphine (3H-NPA) was examined in male rats. The atypical neuroleptics were found to be considerably more potent in displacing nigral than striatal 3H-spiperone binding while the classical neuroleptics were about equipotent in the two brain regions. The benzamides also produced considerably less displacement of 3H-spiperone in the striatum than did classical neuroleptics. Furthermore, while the classical neuroleptic drugs block the striatal 3H-spiperone and 3H-NPA binding sites to about the same degree, the substituted benzamides appear to have a higher affinity for the DA receptors labelled by 3H-NPA than those labelled by 3H-spiperone. The behavioural effects of the benzamides were found to differ from classical neuroleptic drugs particularly with regard to induction of catalepsy. Thus, the induction of cataleptic behaviour was found to correlate with displacement of 3H-spiperone in the striatum while blockade of apomorphine induced hyperactivity correlated with the displacement of spiperone in extrastriatal areas.

Animals↗
PubMed1984

Effect of lipophilicity of substituted benzamides on the dopaminergic effects in vivo and in vitro.

The antidopaminergic potencies of some new substituted benzamides related to remoxipride have been studied in the rat using in vitro (3H-spiperone binding) and in vivo techniques (antagonism of apomorphine induced stereotypies). The lipophilicities of the different benzamides were calculated by the addition of the lipophilic contribution (pi value) of the added substituent. It was found that the in vivo potencies of the compounds were not direct proportional to the in vitro potencies. The discrepancies in the potencies in vitro and in vivo (expressed as the ratio) are correlated to the calculated lipophilicities. Certain substituents in the benzene nucleus affect this in vitro--in vivo ratio more than could be expected from the change in lipophilicity caused by the substituent. The type of side chain is also of great importance. The reasons for the discrepancies between in vitro and in vivo antidopaminergic potencies of the studied substituted benzamides are discussed.

Animals↗
PubMed1983

Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat.

Male rats received the noradrenaline neurotoxin DSP4 (50 mg/kg) 7 days prior to injection of D-amphetamine (10 or 40 mumol/kg i.p.). The hyperactivity induced by D-amphetamine (10 mumol/kg) was significantly reduced by DSP4 pretreatment. However, the increased rearings and the amphetamine-induced stereotypies were not blocked by pretreatment with DSP4. The reduction of amphetamine hyperactivity induced by DSP4 was blocked by pretreatment with the noradrenaline-uptake blocking agent, desipramine, which prevents the neurotoxic action of DSP4. The present results suggest a selective involvement of central noradrenergic neurones in the locomotor stimulant effect of amphetamine in the rat.

Animals↗
PubMed1983

Attenuation of morphine-induced analgesia by p-chlorophenylalanine and p-chloroamphetamine: test-dependent effects and evidence for brainstem 5-hydroxytryptamine involvement.

A number of studies on the role of 5-HT in morphine analgesia and regulation of nociception are reviewed. Highly divergent conclusions are found in the literature with regard to the importance of serotonergic structures. Several methodological differences, particularly with regard to lesion and depletion techniques and testing procedures, may account for the controversies in the literature. The experimental findings presented demonstrate attenuation of morphine-induced analgesia in the hot-plate and tail-flick tests, and increased responsiveness to noxious electrical shock following depletion of 5-HT in ascending and descending 5-HT pathways by PCPA (200 + 100 + 100 mg/kg on 3 consecutive days prior to testing) as well as following destruction of cerebral 5-HT terminals by PCA (2 X 10 mg/kg, 7 and 8 days before testing). This was also the case when the neurotoxic effect of PCA was largely restricted to the brainstem by pretreatment with the 5-HT reuptake inhibitor zimelidine (20 mg/kg prior to each PCA injection). Attenuation of morphine analgesia was not found in the flinch-jump test or in the hot-plate test when conducted immediately after flinch-jump testing. It is concluded that brainstem 5-HT connections may contribute to the analgetic effect of morphine, but only under certain test conditions.

Amphetamines↗
PubMed1983

Chronic antidepressant treatment and central 5-HT synapses.

The present studies have shown that chronic antidepressant treatment with desipramine, imipramine, zimelidine and alaproclate led to adaptive changes in both pre- and postsynaptic 5-hydroxytryptamine (5-HT) receptor mechanisms which appear to result in 5-HT sub- or supersensitivity development depending upon the 5-HT nerve terminal systems analyzed. The results underline the heterogeneity of the central 5-HT neurone systems in their responses to chronic antidepressant treatment. An involvement of 5-HT comodulators is postulated in the actions of antidepressants on central 5-HT synapses. Finally, the results point to the importance of 5-HT neurone systems as targets for the action for antidepressant drugs and they may mediate at least some of the therapeutic activity of antidepressant drugs.

Animals↗