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S O Ogren

Publications and source records attributed to S O Ogren.

At least 73 records · Page 4Linked to original sources
PubMed1997

Nociceptin/orphanin FQ microinjected into hippocampus impairs spatial learning in rats.

The newly discovered peptide nociceptin/orphanin FQ has been found to increase reactivity to pain and to influence locomotor activity after intracerebroventricular administration. This study investigated the possible role of hippocampal nociceptin/orphanin FQ in spatial learning and in spontaneous locomotion. Male rats were trained in the Morris water task after microinjection of 10 nmol nociceptin/orphanin FQ or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal hippocampus. Nociceptin/orphanin FQ was found to severely impair spatial learning without interfering with swimming performance. Intrahippocampal injection of nociceptin/ orphanin FQ markedly decreased exploratory locomotor activity including vertical movements (rearing). The data suggest that nociceptin/orphanin FQ is a potent modulator of synaptic plasticity within the hippocampus.

Animals↗
PubMed1996

On the role of glucocorticoid receptors in brain plasticity.

1. The mapping of glucocorticoid receptors (GR) in the rat central nervous system (CNS) has demonstrated their widespread presence in large numbers of nerve and glial cell populations also outside the classical stress regions. 2. The present paper summarizes the evidence that glucocorticoids via GR in the CNS can act as lifelong organizing signals from development to aging. The following examples are given. (a) In the prepubertal and adult offspring, prenatal corticosterone treatment can produce long-lasting changes in striatal dopaminergic communication. (b) In adulthood, the evidence suggests complex regulation by adrenocortical hormones of neurotrophic factors and their receptors in the hippocampal formation. (c) In aging, the strongly GR-immunoreactive pyramidal cell layer of the CA1 hippocampal area appears to be preferentially vulnerable to neurotoxic actions of glucocorticoids, especially in some rat strains. 3. Strong evidence suggests that each nerve cell in the CNS is supported by a trophic unit, consisting of other nerve cells and glial cells, blood vessels, and extracellular matrix molecules. Due to multiple actions on nerve and glial cell populations of the different trophic units, the glucocorticoids may exert either an overall trophic or a neurotoxic action. It seems likely that with increasing age, the endangering actions of glucocorticoids on nerve cells prevail over the neurotrophic ones, leading to reduced nerve cell survival in some trophic units.

Adrenal Cortex Hormones↗
PubMed1996

Effects of ventral hippocampal galanin on spatial learning and on in vivo acetylcholine release in the rat.

The neuropeptide galanin coexists in the medial septum and diagonal band of Broca with a population of acetylcholine neurons which project mainly to the ventral hippocampus. The present studies investigated the role of ventral hippocampal galanin in spatial learning in the male rat using a spatial learning task. In addition, the effects of galanin on cholinergic function were monitored by in vivo microdialysis and high-performance liquid chromatography. Bilateral microinjections of galanin (3 nmol/ rat) via chronic cannulae placed into the ventral hippocampus (i.v.h.) produced a slight but significant impairment of acquisition of the spatial task, while the 1 nmol dose of galanin facilitated acquisition. The 6 nmol dose of galanin failed to affect performance. A trend for an impairment of long-term memory retention (examined seven days after the last training session) was observed after 3 nmol of galanin, while the 1 nmol dose facilitated retention performance. Scopolamine (0.1 mg/kg, s.c.) caused a marked impairment of acquisition. Galanin (3 nmol/rat) given i.v.h. failed to modify the acquisition impairment caused by scopolamine (0.1 mg/kg, s.c.). These results suggest that galanin given i.v.h. produces a biphasic dose-dependent effects on spatial learning. In freely moving rats, galanin (3 nmol/10 microliters) given into the lateral ventricle (i.c.v.) did not affect basal acetylcholine release. In contrast, perfusion (100 min) with galanin (0.1 or 0.3 nmol/1.25 microliters/min) through the ventral hippocampal probe resulted in a reduction of basal acetycholine release which was dose-dependent and reversible. Galanin given i.c.v. (3 nmol/10 microliters) or through the probe (0.3 nmol/1.25 microliters/min) attenuated the increase in acetylcholine release evoked by the muscarinic antagonist scopolamine (0.1 mg/kg, s.c.; 0.001 nmol/1.25 microliters/min through the probe). The galanin plus scopolamine combinations produced a 50% lower increase in the extracellular acetylcholine concentrations than scopolamine alone. This suggests that the mechanism(s) behind scopolamine- and galanin-induced stimulation of acetylcholine differ. These results indicate that ventral hippocampal galanin plays a role in cognition and that it has a powerful and modulatory effect on cholinergic transmission. However, the effects of exogenous galanin on spatial learning cannot be directly related to changes in in vivo cholinergic transmission in the ventral hippocampus. These discrepancies may relate to effects on subtypes of galanin receptors with different functional coupling. In addition, other hippocampal neurotransmitter systems (e.g. noradrenergic neurons) important for cognitive functions may also be modulated by ventral hippocampal galanin.

Acetylcholine↗
PubMed1996

Dopamine D1 receptor-mediated facilitation of GABAergic neurotransmission in the rat strioentopenduncular pathway and its modulation by adenosine A1 receptor-mediated mechanisms.

By using in vivo microdialysis it was found that one of the main functions of striatal dopamine D1 receptors is to selectively facilitate GABAergic neurotransmission in the 'direct' strioentopeduncular pathway. D1 receptors localized in the entopeduncular nucleus were also found to facilitate GABA release. However, results obtained from in vivo microdialysis, in vivo electrochemistry, immunohistochemistry and confocal laser microscopy suggested that entopeduncular D1 receptors could only be activated under pharmacological conditions. Adenosine A1 receptors were found to antagonistically modulate the D1-mediated regulation of the strioentopeduncular pathway. Furthermore, using in situ hybridization D1 and A1 receptors were shown to be colocalized in medium-sized striatal neurons. These results show that the strioentopeduncular neuron is a main locus for adenosine-dopamine interactions in the brain.

Animals↗
PubMed1995

Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo.

Glial-cell-line-derived neurotrophic factor (GDNF), a recently cloned new member of the transforming growth factor-beta superfamily, promotes survival of cultured fetal mesencephalic dopamine neurons and is expressed in the developing striatum. There have, however, been no reports about effects of GDNF in situ. We have used the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces parkinsonian symptoms in man, to determine whether GDNF might exert protective or regenerative effects in vivo in the adult nigrostriatal dopamine system in C57/B1 mice. GDNF injected over the substantia nigra or in striatum before MPTP potently protects the dopamine system, as shown by numbers of mesencephalic dopamine nerve cell bodies, dopamine nerve terminal densities and dopamine levels. When GDNF is given after MPTP, dopamine levels and fibre densities are significantly restored. In both cases, motor behaviour is increased above normal levels. We conclude that intracerebral GDNF administration exerts both protective and reparative effects on the nigrostriatal dopamine system, which may have implications for the development of new treatment strategies for Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Hyperactivity in neonatally dopamine-lesioned rats requires residual activity in mesolimbic dopamine neurons.

Neonatal destruction of mesencephalic dopamine (DA) neurons in rats through administration of 6-hydroxydopamine (6-OHDA; 75 micrograms IC) leads to locomotor hyperactivity at adulthood. Treatment with the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (H44/68; 250 mg/kg) was shown to reduce the motor activity of neonatally 6-OHDA-lesioned rats to activity levels similar to controls. In both animal groups, DA and metabolite tissue levels decreased after the H44/68 treatment. However, the extent of the H44/68-induced DA decrease was less pronounced in the 6-OHDA-lesioned animals, with no change at all in the dorsal striatum. These results imply that residual activity in mesolimbic DA neurons is required for maintaining the hyperactivity seen after neonatal 6-OHDA lesions, and that this hyperactivity is apparently mediated by postsynaptic alterations.

Animals↗
PubMed1995

Prenatal corticosterone increases spontaneous and d-amphetamine induced locomotor activity and brain dopamine metabolism in prepubertal male and female rats.

Recently, both glucocorticoid receptor immunoreactivity and glucocorticoid receptor messenger RNA levels were found in multiple brain areas, especially in the neuroepithelium during the late prenatal development of the rat brain. To better understand the potential influence of stress on fetal brain development by release of maternal adrenocortical steroids, we have investigated the effects of corticosterone administration to pregnant rats on the locomotor activity of their prepubertal offspring. On day 16 of pregnancy female rats were implanted with either placebo or corticosterone pellets (release of 2.4 mg/day for seven days). After birth their offspring were nursed by foster mothers to avoid any postnatal effects of the corticosterone pellets. At three weeks of age, the offspring were tested for spontaneous motor behaviours. Both male and female offspring from corticosterone treated mothers showed significantly increased spontaneous ambulation, motility and rearing compared to placebo treated groups. No significant sex differences were found in locomotor activity between male and female offspring from placebo groups. Following d-amphetamine (1.5 mg/kg) treatment, a preferential dopamine releasing agent, we observed a significant increase in ambulation, motility and rearing activity in the male offspring treated with corticosterone. In the female offspring, only the rearing activity was significantly higher after d-amphetamine treatment in the prenatal corticosterone group compared with the placebo treated group. Basal dopamine metabolism (dihydroxyphenylacetic acid/dopamine ratio) was increased in the dorsal striatum and ventral striatum of male and female offspring from corticosterone-treated dams. In the male offspring, corticosterone treatment was associated with a disappearance of the right side dominance of dopamine metabolism in the dorsal striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Nicotine treatment counteracts perinatal asphyxia-induced changes in the mesostriatal/limbic dopamine systems and in motor behaviour in the four-week-old male rat.

In the present study, the effects of nicotine treatment on the changes induced by perinatal asphyxia in exploratory and D-amphetamine-induced behaviour, and in the number of brain tyrosine hydroxylase-immunoreactive nerve cell bodies were investigated in four-week-old male rats. Asphyxia was induced in pups by placing the fetuses, still in their uterus horns removed by hysterectomy from full-term pregnant rats, in a 37 degrees C water bath for 15-16 min or 19-20 min. Surviving male pups were treated with nicotine via suckling from surrogate mothers implanted subcutaneously with Alzet minipumps containing nicotine (0.2 mumol/kg per h) for four weeks. The minipumps implanted in the mothers of sham-treated animals contained saline only. After treatment, exploratory behaviour and D-amphetamine-induced behaviour was analysed in a computerized "activity" box. After the behavioural experiments, the rats were taken for tyrosine hydroxylase immunohistochemistry, and the total number of tyrosine hydroxylase immunoreactive cell bodies were counted in the A9 and A10 regions of the substantia nigra and the ventral tegmental area, respectively. Nicotine serum levels were measured using gas chromatography in selected asphyctic and control pups at different periods after delivery. During the exploratory phase, in saline-nurtured rats, 15-16 min of asphyxia slightly increased (approximately 25%) locomotion, motility and rearing. In contrast, 19-20 min of asphyxia reduced the locomotion and rearing by approximately 50%, as compared to controls. An increase in amphetamine-induced behaviours was observed after 15-16 min, but not after 19-20 min of asphyxia, as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Clomipramine and clonazepam increase cholecystokinin levels in rat ventral tegmental area and limbic regions.

Recent reports suggest that a cholecystokinin (CCK)-related dysfunction may be a target by which drugs can modulate anxiety and panic disorders. In the present study, effects of subchronic (14 days) treatment with the monoamine uptake inhibitors nortriptyline (30 mumol/kg per day), amitriptyline (29 mumol/kg per day), clomipramine (32 mumol/kg per day) and alaproclate (39 mumol/kg per day), as well as with the benzodiazepine clonazepam (0.25 mumol/kg per day), on rat brain levels of CCK- and substance P-like immunoreactivity, were compared. The drugs were administered by continuous s.c. infusion using implanted osmotic pumps. The plasma concentrations of the monoamine uptake inhibitors were similar after 1 and 2 weeks of treatment, indicating that steady-state plasma levels had been reached during the first week. Treatment with clomipramine or clonazepam increased the CCK-like immunoreactivity level in the ventral tegmental area (by 64.4 +/- 28.8% and 105.1 +/- 28.8%, respectively) and in the cingulate cortex (by 30.3 +/- 10.1% and 36.0 +/- 11.8%, respectively) (P < 0.05 or P < 0.01). Clomipramine also significantly increased the CCK-like immunoreactivity level in the periaqueductal grey by 85.1 +/- 29.7%. Neither nortriptyline nor amitriptyline or alaproclate produced any significant alterations in the CCK- or substance P-like immunoreactivity levels in the areas examined. The present results may suggest that an altered utilization of CCK in limbic circuits could be of importance for the well documented clinical effect of clomipramine and clonazepam in panic disorders.

Amitriptyline↗
PubMed1994

Chronic haloperidol treatment leads to an increase in the intramembrane interaction between adenosine A2 and dopamine D2 receptors in the neostriatum.

Stimulation of adenosine A2 receptors (with the selective adenosine A2 agonist CGS 21680) in rat striatal membrane preparations, produces a decrease in both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G protein. This intramembrane A2-D2 interaction might be responsible for the behavioural depressant effects of adenosine agonists and for the behavioural stimulant effects of adenosine antagonists such as caffeine and theophylline. Dopamine denervation induces an increase in the intramembrane A2-D2 interaction, which may underlie the observed higher sensitivity to the behavioural effects induced by adenosine antagonists found in these animals. The present study was designed to examine if chronic treatment with haloperidol, which also produces dopamine receptor supersensitivity, is also associated with an increase in the intramembrane A2-D2 interaction in the neostriatum and with a higher sensitivity to the behavioural effects induced by adenosine antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

Effects of typical and atypical antipsychotic drugs on two-way active avoidance. Relationship to DA receptor blocking profile.

The dose-dependent and time-dependent effects of the novel antipsychotic compound remoxipride, as well as the reference compounds chlorpromazine, clozapine, haloperidol, pimozide and sulpiride upon the retention of two-way active avoidance (conditioned avoidance responses, CARs) were studied in male rats. The dose-dependent effects of remoxipride as well as haloperidol and chlorpromazine on the acquisition of CARs were also studied. The acquisition and retention of CARs were tested in shuttleboxes using a 1.0-mA shock intensity and a 10-stone signal (1000 Hz). All the compounds studied, including remoxipride, caused a dose-dependent impairment of acquisition and retention of CARs. The effect of remoxipride on CAR acquisition correlated with remoxipride's effectiveness to block the hyperactivity induced by the dopamine (DA) agonist apomorphine. Unlike chlorpromazine and haloperidol, the potency of remoxipride and clozapine for antagonising CAR retention was found at dose levels much lower than those producing cataleptic effects or blocking apomorphine-induced stereotypies. Based on the DA receptor blocking profile and the relative effectiveness to block CAR it is concluded that the mechanism(s) by which clozapine and remoxipride affect CAR differ from typical neuroleptic drugs. This difference may reflect an action upon different subtypes of functionally coupled DA D2 receptors.

Animals↗
PubMed1994

The dopamine D2 antagonist remoxipride acts in vivo on a subpopulation of dopamine D2 receptors.

Dopamine D2 receptors were inactivated by N-ethoxycarbonyl-2-ethoxy-1,2,-dihydroxy-quinoline (EEDQ) (6 mg/kg i.p.). The reduction in dopamine receptors was monitored by quantitative receptor autoradiography using [125I]iodosulpiride or [3H]raclopride as radioligands. Pretreatment of male rats with haloperidol (0.3-3 mumol/kg i.p.) produced a dose-related, complete protection against the decrease in [125I]iodosulpiride binding induced by EEDQ in the dorsal and ventral striata and in all cortical areas examined. Raclopride (0.25-10 mumol/kg i.p.) produced the same pattern of effect as haloperidol but had a weaker effect. In contrast, remoxipride (1-40 mumol/kg i.p. or s.c.) only produced a partial protection against the dopamine D2 receptor inactivation by EEDQ. The results in the EEDQ test were related to the potency to block d-amphetamine-induced hyperlocomotion and the ability to induce bar-test catalepsy in the rat. The potencies in the behavioural tests were found to correspond to the in vivo occupancy for dopamine D2 receptors as evaluated by the EEDQ-induced decrease in D2 binding. However, remoxipride differed from both haloperidol and raclopride by showing a much reduced occupancy of dopamine D2 receptors at doses with behaviourally equipotent effects. The results support earlier suggestions that remoxipride in vivo may act on a subpopulation of dopamine D2 receptors.

Animals↗
PubMed1994

Phencyclidine- and dizocilpine-induced hyperlocomotion are differentially mediated.

The dopamine (DA) D2 agonist quinpirole and the D2 receptor antagonists, haloperidol, raclopride, and remoxipride, were examined for their ability to block the locomotion induced by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine (PCP) and dizocilpine, both given in equipotent doses. Quinpirole, given in a "DA D2 autoreceptor selective" dose (0.01 mg/kg), failed to influence the motor stimulation by PCP. On the other hand, the locomotor response induced by dizocilpine was significantly reduced by quinpirole. The three DA receptor antagonists blocked dose dependently the motor stimulation produced by both the low (2 mg/kg) and the high dose (3 mg/kg) of PCP. Haloperidol and remoxipride also blocked dose dependently and fully the stimulation produced by the low dose (0.1 mg/kg) of dizocilpine, whereas raclopride partially reduced the effect. The motor stimulation produced by the high doses of dizocilpine (0.2 mg/kg) and PCP (3 mg/kg) was reduced by haloperidol and raclopride only in cataleptogenic doses. Remoxipride, in contrast, fully blocked the effects of both PCP (3 mg/kg) and dizocilpine (0.2 mg/kg) in noncataleptogenic doses. These data suggest that different mechanisms of action may account for the motor stimulatory effects of PCP and dizocilpine. At the presynaptic level, PCP and dizocilpine may differ in the way they act on "regulatory" NMDA receptors controlling neuronal activity in midbrain neurons, and at the postsynaptic level they may interact with subtypes of NMDA receptors differentially coupled to subpopulations of D2 receptors.

Analysis of Variance↗
PubMed1994

Persistent effects of 80 ppm toluene on dopamine-regulated locomotor activity and prolactin secretion in the male rat.

Neurotoxicology 15(3): 621-624, 1994. In the present study we have investigated the effects of toluene exposure (80 ppm, 4 weeks, 5 day/week, 6 h/day) on the serum levels of prolactin, and elaborated our earlier findings about persistent effects of toluene exposure on apomorphine-induced (1 mg/kg, s.c.) locomotor activity. We found that the serum levels of prolactin were increased by 67% in the toluene-exposed rats, as analyzed 17 days after the last exposure. The locomotor activity counts of the control rats were not normally distributed before log-transformation, since most rats showed a low level of activity and only a few showed a very high activity level. The toluene-exposed rats showed a higher level of apomorphine-induced locomotion and motility but not rearing, as analyzed 17 days after the last exposure, whereas spontaneous locomotor activity was unaffected. These results indicate that subacute exposure to 80 ppm of toluene causes persistent impairments in dopamine-mediated neurotransmission.

Animals↗
PubMed1993

Differential effects of the putative galanin receptor antagonists M15 and M35 on striatal acetylcholine release.

The putative galanin receptor antagonists M15 and M35 were examined for their effects on the basal and the galanin-evoked release of acetylcholine in the striatum. Extracellular concentrations of acetylcholine were measured in male rats using in vivo microdialysis and high pressure liquid chromatography techniques. Galanin (300 microM or 3 nmol/10 microliters), perfused through the microdialysis membrane into the striatum, enhanced (100% increase) basal acetylcholine release. M35 (300 microM or 3 nmol/10 microliters) also stimulated the basal acetylcholine release to some extent (about 50%) while M15 at the same concentration failed to do so. When M15 and M35 were coinfused with galanin, the galanin-evoked acetylcholine release was blocked completely by M15 (300 microM or 3 nmol/10 microliters) but only partially by M35 (300 microM or 3 nmol/10 microliters). The increase in acetylcholine release induced by M35 (300 microM) was blocked by M15 (300 microM). It is concluded that M15 is a full galanin receptor antagonist while M35 behaves as a mixed agonist-antagonist in vivo in the rat striatum. Both M15 and M35 fully displaced 0.2 nM [125I]galanin from its binding sites in the striatal membranes. The Hill coefficient of these [125I]galanin displacement curves with M15 and M35 was 0.4-0.5 compared to unity in the case of galanin. Analysis of the displacement curves suggested that both M15 and M35 recognized two classes of galanin binding sites in striatal membranes of the rat. To explain the difference between M15 and M35 it is suggested that there may exist a putative subtype of galanin receptor in the striatum, which is differentially affected by M15 and M35.

Acetylcholine↗
PubMed1993

Galanin stimulates striatal acetylcholine release via a mechanism unrelated to cholinergic receptor stimulation.

The effect of galanin (GAL) on the basal and the muscarinic agonist/antagonist mediated release of acetylcholine (ACh) in the striatum was investigated in male rats using in vivo microdialysis and HPLC techniques. GAL (300 microM or 3 nmol/10 microliters), perfused through the microdialysis membrane into the striatum, was found to enhance basal ACh release. The GAL evoked ACh release was completely prevented by bupivacaine, a sodium channel blocker (1.5 mM) when coperfused with GAL. This suggests that the effect of GAL depends on intact neuronal activity and thus derives from impulse-dependent release. The muscarinic agonists oxotremorine (0.3 mg/kg, i.p.) or carbachol (100 microM, infusion) reduced ACh release and reduced the stimulation of ACh release by GAL with a magnitude corresponding to that of oxotremorine or carbachol alone. Thus, the resultant effect of GAL on ACh release remained unchanged. When GAL was given at a threshold dose (30 microM), which by itself did not stimulate ACh release, it was unable to attenuate the muscarinic agonist induced inhibition of ACh releases. Furthermore, GAL given in combination with scopolamine (0.25 mg/kg, i.p.) or pirenzepine (1 microM, infusion) added to the stimulating effect by the two muscarinic antagonists. In contrast to the GAL (300 microM) evoked ACh release, the scopolamine (0.25 mg/kg, i.p.) stimulated ACh release was not blocked by M15, a putative GAL antagonist, indicating that the mechanisms behind GAL and scopolamine evoked striatal ACh release differ. These results suggest that the mechanisms behind GAL evoked release do not involve direct interactions with pre- or postsynaptic muscarinic receptor mediated events. It is concluded that the stimulation of the basal ACh release by GAL in the striatum occurs via occupation of GAL receptors located on cholinergic interneurons and that the release process is dependent on intact neuronal activity.

Acetylcholine↗
PubMed1993

Persistent effects of subchronic toluene exposure on spatial learning and memory, dopamine-mediated locomotor activity and dopamine D2 agonist binding in the rat.

The effects of subchronic inhalation exposure to toluene (80 ppm, for 4 weeks, 5 days/week, 6 h/day) was studied on spatial learning (postexposure days 3-6) and memory (postexposure day 14) using a water maze, on spontaneous and apomorphine-induced (1 mg/kg, subcutaneously (s.c.)) locomotor activity (postexposure day 17) and on the binding parameters of the dopamine D2 agonist S(-)[N-propyl-3H(N)]propylnorapomorphine ([H]NPA) in membrane preparations of the neostriatum of the rat. Toluene treatment was found to cause a statistically significant impairment in acquisition and retention of the spatial learning task. Furthermore, toluene significantly increased (2-fold) apomorphine-induced locomotion and caused a trend for a 50-60% increase in motility without any significant effect on rearing. Spontaneous locomotion, motility and rearing were not affected by toluene. Toluene treatment produced a significant 30-40% increase in the Bmax values of [3H]NPA and a trend for a 20-30% increase in the KD values. These results indicate that subchronic exposure to toluene in low concentrations causes a slight but persistent deficit in spatial learning and memory, a persistent increase in dopamine-mediated locomotor activity and an increase in the number of dopamine D2 receptors in the rat.

Administration, Inhalation↗