Search PubMed⌕ Search

Biomedical subjects

S O Ogren

Publications and source records attributed to S O Ogren.

At least 37 records · Page 2Linked to original sources
PubMed2000

Decreased 5-HT transporter mRNA in neurons of the dorsal raphe nucleus and behavioral depression in the obese leptin-deficient ob/ob mouse.

The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) is an important regulator of feeding behavior. A hypothalamic site of action for 5-HT in body weight control is supported by the presence of 5-HT receptors in hypothalamic regions which are intimately associated with regulation of food intake. In the present study we have investigated whether there may be an interaction between the hormone leptin, an adipose tissue-derived cytokine signaling factor that inhibits food intake and lowers body weight, and the brain serotonergic system. Immunohistochemical analysis of colchicine-treated rats showed colocalization of 5-HT transporter- and leptin receptor-immunoreactivity in cell bodies of the dorsal raphe nucleus, suggesting that dorsal raphe neurons are targets for circulating leptin. Levels of 5-HT transporter mRNA expression were compared in neurons of the dorsal raphe nucleus of obese leptin-deficient ob/ob mice and their lean littermates using in situ hybridization. 5-HT transporter mRNA levels were significantly down-regulated in neurons of the dorsal raphe nucleus of obese ob/ob mice as compared to lean control mice. Behavioral analysis showed that obese ob/ob mice had significantly lower locomotor activity and exhibited increased immobility in Porsolt's test, a model for depression. Taken together, these results suggest that serotonergic cell bodies in the rodent dorsal raphe nucleus possess leptin receptors and that the serotonergic system, as reflected by expression levels of 5-HT transporter mRNA, is down-regulated in the obese behaviorally depressed ob/ob mouse.

Adipose Tissue↗
PubMed2000

Galanin and spatial learning in the rat. Evidence for a differential role for galanin in subregions of the hippocampal formation.

Anatomical, neurochemical and behavioural evidence support a role for galanin in hippocampally mediated functions such as spatial learning and memory. To obtain more precise information on this role, galanin (3 nmol/rat) was infused via bilateral chronic cannulae into different areas of the hippocampal formation which are characterized by different galanin receptor subtypes and also by different galanin innervation patterns. The effects of infused galanin on spatial learning were examined in the Morris swim maze. Infusions of galanin into both the dorsal and ventral dentate gyrus, which mainly contain GAL-R2 receptor mRNA and a high degree of galanin-noradrenaline coexistence, significantly retarded spatial acquisition without affecting swim speed or performance in the visible platform test. This spatial learning deficit was fully blocked by pretreatment with the non-selective galanin antagonist M35. Analysis of retention performance suggested that the major effect of intrahippocampal galanin is mediated via a specific disruption of acquisition mechanisms of importance for performance in the probe trial. Galanin infused into the ventral CA1 (a mainly GAL-R1 receptor mRNA expressing region) or into anterior, ventral CA3 regions did not produce any deficits in spatial learning compared to control animals. These results suggest that galanin mediates its action on spatial learning mainly through the GAL-R2 receptor subtype in areas where most of the galanin is present in noradrenergic terminals. A possible role for the GAL-R1 receptor subtype in cognition in the dorsal and ventral hippocampus remains to be defined. The results suggest a differential functional role for galanin and galanin receptor subtypes within subregions of the hippocampal formation.

Animals↗
PubMed2000

Ontogeny of the motor inhibitory role of dopamine D(3) receptor subtype in rats.

We have examined the motor responses to the dopamine D(3) receptor-preferring agonist, S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-1-benzopyranol[4,3-b]-1,4-oxazin+ ++-9-ol ((+)-PD128,907), by non-habituated male rats during postnatal development. (+)-PD128,907 (0.025 and 0.1 mg/kg) increased motor activity (rearing, motility and locomotion) in 14-day-old rats without inducing oral stereotypies. However, in 21-, 28- and 70-day-old rats, (+)-PD128,907 caused a significant reduction in motor activity. This reduction was most pronounced in 70-day-old rats. In addition, the stimulatory effects of (+)-PD128,907 in 14-day-old rats were fully blocked by the dopamine D(3) receptor antagonist 5,6-dimethoxy-2-(di-u-propylamino) indan (U99194A). These results suggest that the motor inhibition mediated by the activation of the dopamine D(3) receptors develops between the second and the third postnatal weeks.

Age Factors↗
PubMed2000

Galanin-(1-16) modulates 5-HT1A receptors in the ventral limbic cortex of the rat.

The aim of the present study was to evaluate whether galanin-(1-16) of the rat and porcine type and rat galanin-(1-29) can modulate the 5-HT1A receptors, using [3H]8-OH-DPAT as a radioligand, in membrane preparations from the ventral limbic cortex of the rat. Galanin-(1-16) produced a concentration dependent increase in the Kd value of [3H]8-OH-DPAT binding sites with a maximal effect of approximately 61% at 30 nM without changing the Bmax values. The galanin antagonist M35 blocked these effects. Rat galanin produced the same pattern of response but was less potent and effective. These results indicate the existence of a galanin receptor subtype in the ventral limbic cortex mainly recognizing N-terminal galanin fragments and capable of more strongly modulating 5-HT1A receptors than cloned galanin receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Genetic evidence that cocaine and caffeine stimulate locomotion in mice via different mechanisms.

The effects of cocaine and caffeine on motor activity in two mouse strains 129/OlaHsd (129) and C57BL/6J (C57) were compared. The former mice exhibited lower basal motor activity than the latter. Cocaine (3, 10, 30 mg/kg) injected i.p. in habituated C57 mice produced a dose-dependent increase in rearing, motility and locomotion. In 129 mice, little or no stimulation was seen and only with the highest dose of cocaine. In both strains caffeine (3, 15, 30 mg/kg) produced a dose-dependent increase in rearing, motility and locomotion. The effect of caffeine on rearing was greater in C57 than in 129 mice, but motility and locomotion were stimulated approximately to the same degree in both strains. Thus, differences in the sensitivity to caffeine and cocaine between mouse strains provide genetic evidence that these two stimulants probably produce locomotor stimulation via somewhat different mechanisms.

Animals↗
PubMed2000

Internalization of intracerebrally administered porcine galanin (1-29) by a discrete nerve cell population in the hippocampus of the rat.

In spite of numerous studies utilizing intraventricular administration of porcine galanin (1-29), little is known about the spread and cellular distribution of exogenous galanin following intraventricular administration. In this study a discrete nerve cell body population with their dendrites became strongly galanin immunoreactive (IR) in the dorsal hippocampus following intraventricular porcine galanin (1.5 nmol/rat). Time course experiments showed that after time intervals of 10 and 20 min, but not at 60 min, scattered small- to medium-sized galanin-IR nerve cell bodies and their dendrites were present in all layers of the dorsal and ventral hippocampus. In double-immunolabeling experiments most of these nerve cells were identified as putative GABA interneurons costoring NPY-IR or somatostatin-IR in some cases. Twenty minutes after intraventricular injection of artificial cerebrospinal fluid (aCSF), only endogenous punctate and coarse galanin-IR terminals were found, but no galanin-IR cell bodies. Intrahippocampal injection of fluorophore-labeled galanin resulted in the appearance of fluorescent nerve cell bodies with the same morphology and localization as in the above experiments. Coadministration of the putative galanin antagonist M35 (0.5 nmol) and galanin (1.5 nmol) resulted in a reduced number of galanin-IR nerve cell bodies in the hippocampus of half of the rats. These findings support the existence of a population of putative hippocampal GABA interneurons with the ability to internalize and concentrate galanin and/or its fragments present in the extracellular fluid, possibly mediated by galanin receptors.

Animals↗
PubMed2000

Multiple 5-HT receptors in passive avoidance: comparative studies of p-chloroamphetamine and 8-OH-DPAT.

The aim of this study was to examine the involvement of multiple 5-HT receptors in passive avoidance (PA) with a focus on 5-HT1A, 5-HT2A, and 5-HT2C receptors. Because increases in 5-HT transmission result in concomitant multiple 5-HT receptor activation, the effects of the 5-HT releasing compound p-chloroamphetamine (PCA) were compared with those of the selective 5-HT1A receptor agonist 8-OH-DPAT in the rat. In addition, some results with the nonselective 5-HT2C/2B/1B receptor agonist mCPP are presented. When injected before PA training, 8-OH-DPAT, mCPP, and PCA produced a dose-related impairment of the 24-hour retention. The crucial involvement of the postsynaptic 5-HT1A receptors in the action of 8-OH-DPAT was confirmed. Thus, the 5-HT1A receptor antagonists WAY 100635 and (-)-pindolol blocked the PA deficit by 8-OH-DPAT. The impairment of PA caused by PCA was attenuated by WAY 100635 and (-)-pindolol, suggesting an involvement of the 5-HT1A receptor. In contrast, the 5-HT2A and 5-HT2C receptors were of negligible importance in the 24-hour retention deficit induced by PCA. However, the ability of the 5-HT2C receptor antagonist Ro 60-0491 to block the inhibitory effects of mCPP indicated an important regulatory role of the 5-HT2C receptor in PA. The nonselective 5-HT receptor antagonist methiothepin attenuated the PA deficit by PCA but lacked activity versus 8-OH-DPAT. These data provide evidence for the hypothesis that, in addition to the 5-HT1A receptor, other 5-HT receptor subtypes are involved in the inhibitory actions of PCA. Importantly, changes in dopamine transmission seemed not to contribute to the PA impairment by PCA. The behavioral alterations caused by the drug treatments at the time of PA training could not be related to the subsequent retention performance. In conclusion, multiple 5-HT receptors are involved in PA with roles that probably differ at various stages of information processing. These findings also suggest that there probably exists a functional distinction between 5-HT receptor subtypes in different types of aversive learning.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Dose- and time-dependent bimodal effects of kappa-opioid agonists on locomotor activity in mice.

The kappa-opioid agonists U50488H, bremazocine, and BRL52537, and the mu-opioid agonist morphine were compared in their ability to modify spontaneous motor activity in male NMRI mice. Higher, analgesic doses of the kappa-agonists reduced rearing, motility, and locomotion in nonhabituated mice. These effects, as well as the analgesic action of U50488H, were blocked by the selective kappa-opioid antagonists nor-binaltorphimine and DIPPA. In contrast, lower, subanalgesic doses (1.25 and 2.5 mg/kg for U50488H; 0.15 and 0.075 mg/kg for bremazocine, and 0.1 mg/kg for BRL52537) time dependently increased motor activity. The stimulatory effects of U50488H and bremazocine were not observed in habituated animals and were reduced by dopamine depletion. Surprisingly, the stimulatory effects of U50488H and bremazocine were not blocked by nor-binaltorphimine and DIPPA but they were completely eliminated by naloxone (0.1 mg/kg). The effects of morphine were dose-dependent; an initial limited suppression was followed by increased motility and locomotion (but not rearing) with a peak effect at 20 mg/kg both in habituated and nonhabituated mice. The selective mu-opioid antagonist beta-funaltrexamine blocked morphine-induced motor stimulation and analgesia but failed to affect the analgesic and motor stimulatory effects of U50488H. The results indicate that kappa-opioid agonists interact with different functional subtypes of opioid receptors. A stimulatory, naloxone-sensitive but nor-binaltorphimine- and DIPPA-insensitive subtype of opioid receptor appears to operate only when the dopamine system is tonically active in nonhabituated animals. At higher doses, kappa-agonists produce analgesia and motor suppression, effects mediated by a "classic" (inhibitory) kappa-opioid receptor.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Galanin and learning.

A number of studies indicate that galanin (GAL) is a potent modulator of basal acetylcholine release in the rat forebrain e.g. in the cholinergic neurons of the septo-hippocampal projections. Thus, GAL perfused through the microdialysis probe decreased basal acetylcholine release in the ventral hippocampus, while it enhanced acetylcholine release in the dorsal hippocampus. This finding indicates that GAL may act via different mechanisms within the subsystems of the hippocampus. This hypothesis has received support from studies using the Morris swim maze, a learning task dependent on hippocampal mechanisms. GAL (3 nmol/rat) infused into the ventral hippocampus impaired spatial learning acquisition, while it tended to facilitate when injected into the dorsal hippocampus. However, the effects of GAL on acetylcholine release and on spatial learning, which are due to activation of GAL-receptors, appear to be indirectly mediated possibly via noradrenaline transmission. GAL is also a potent inhibitor of mesencephalic 5-HT neurotransmission in vivo. These findings are discussed in relation to the role of acetylcholine and serotonin in cognition.

Acetylcholine↗
PubMed1999

Effect of N-methyl-D-aspartate on motor activity and in vivo adenosine striatal outflow in the rat.

It has been previously found that the systemic administration of low doses of N-methyl-D-aspartate (NMDA) in mice induces motor depression. The effects of the systemic administration of different doses of NMDA (10, 30 and 60 mg/kg s.c.) on the motor activity and on the in vivo extracellular levels of adenosine in the striatum was studied in Sprague-Dawley rats. The adenosine concentration in samples of perfusate was determined 24 h after implantation of a transverse microdialysis probe. At 30 and 60 mg/kg, but not 10 mg/kg, NMDA induced both a significant motor depression (motility and rearing) and a significant increase in the striatal extracellular levels of adenosine. Both the motor depression and the changes in the extracellular levels of adenosine were only evident during the first 30 min after NMDA administration. The non-competitive NMDA receptor antagonist MK-801 (0.1 mg/kg s.c.) completely counteracted the effects of NMDA (30 mg/kg s.c.) on motor activity (motility) and on the striatal extracellular levels of adenosine. The correlation between the behavioural and the biochemical data strongly support the hypothesis that adenosine release in the striatum is a main mechanism responsible for the motor depressant effects produced by the systemic administration of NMDA.

Adenosine↗
PubMed1999

A behavioral analysis of the spatial learning deficit induced by the NMDA receptor antagonist MK-801 (dizocilpine) in the rat.

This study analyzes whether the disruptive effects of the noncompetitive NMDA receptor antagonist MK-801 (0.01-0.1 mg/kg s.c.) on spatial learning can be dissociated from sensorimotor disturbances in the rat. Two different modifications of the Morris swim maze task with a hidden underwater platform were used: with or without local cue. Retention was tested either 24 h or 7 days after training as a probe trial (without platform). The present data indicate that MK-801 produces an impairment of spatial learning that cannot be dissociated from motor or sensory mechanisms. These findings support the view that NMDA receptors probably contribute to, but are not essential for, spatial learning in the water maze.

Animals↗
PubMed1998

Galanin modulates 5-hydroxytryptamine functions. Focus on galanin and galanin fragment/5-hydroxytryptamine1A receptor interactions in the brain.

The reciprocal interactions between galanin and 5-HT1A receptors in the rat brain are presented. Galanin and its NH2-terminal fragments antagonize 5-HT1A receptor-mediated transmission at the postjunctional level, whereas galanin receptor activation mimics the inhibitory action of 5-HT1A receptor activation at the soma-dendritic level, leading to reductions of 5-HT metabolism and release. These interactions have been shown in both receptor binding studies and functional studies. In view of the present findings, galanin antagonists may represent a new type of anti-depressant drug, based on the 5-HT hypothesis of depression, by enhancing 5-HT release and postjunctional 5-HT1A-mediated transmission. Moreover, following intracerebroventricular injection galanin was found to be internalized in a population of hippocampal nerve cells mainly representing GABA, somatostatin, and/or NPY-immunoreactive nerve cells. The relevance of these findings is discussed in relation to the concept of volume transmission.

Animals↗
PubMed1998

Modulation of acetylcholine and serotonin transmission by galanin. Relationship to spatial and aversive learning.

This paper presents evidence that galanin is a potent in vivo modulator of basal acetylcholine release in the rat brain with qualitatively and quantitatively differential effects in the dorsal and ventral hippocampus. Galanin perfused through the microdialysis probe decreased basal acetylcholine release in the ventral hippocampus, while it enhanced acetylcholine release in the dorsal hippocampus. Galanin (3 nmol/rat) infused into the ventral hippocampus impaired spatial learning acquisition, while it tended to facilitate acquisition when injected into the dorsal hippocampus. These effects appear to be related to activation of GAL-R1 (ventral hippocampus) and GAL-R2 (dorsal hippocampus) receptors, respectively. However, the effects of galanin on acetylcholine release and on spatial learning appear not to be directly related to cholinergic mechanisms, but they may also involve interactions with noradrenaline and/or glutamate transmission. Galanin administered into the lateral ventricle failed to affect acetylcholine release, while this route of administration produced a long-lasting reduction in 5-HT release in the ventral hippocampus, indicating that galanin is a potent inhibitor of mesencephalic 5-HT neurotransmission in vivo. Subsequent studies supported this hypothesis, showing that the effects on 5-HT release in vivo are most likely mediated by a galanin receptor in the dorsal raphe. The implications of these findings are discussed in relation to the role of acetylcholine in cognitive functions in the forebrain and the role of the raphe 5-HT neurons in affective disorders.

Acetylcholine↗
PubMed1998

Simultaneous determination of acetylcholine, choline and physostigmine in microdialysis samples from rat hippocampus by microbore liquid chromatography/electrochemistry on peroxidase redox polymer coated electrodes.

Microbore column liquid chromatography with post-column immobilized enzyme reactor (IMER) and electrochemical detection on redox polymer coated electrodes was used for detection of acetylcholine (ACh) and choline (Ch) in microdialysis samples. The sensitivity of the coated electrodes, decreased gradually by about 10%/day, with highest reduction of 30% within the first 16 h of use. A number of choline derivatives were tested as possible internal standards, of those acetylethylhomocholine (AEHCh) and butyrylcholine (BCh) were found the most suitable candidates since they both provided high enzymatic conversion in the IMER. Physostigmine produced a negative peak, possibly reflecting oxidation of eseroline--a decarbamoylated product of reversible reaction of physostigmine with immobilized acetylcholine esterase. The probes, implanted in the ventral hippocampi of awake rats were perfused at a flow-rate of 1.25 microl/min with Ringer solution containing 10 microM physostigmine or with artificial cerebrospinal fluid only. The concentrations of ACh in 10-microl samples at basal conditions were between 0.9-2.5 nM, whereas in the presence of physostigmine the ACh levels raised to 41-48 nM. Physostigmine concentration was reduced to 8.8 microM, indicating its in vivo delivery of about 12%. The coefficients of variation were reduced from 7.4% for external standard method after every sixth sample to 5.8% and 5.9% for internal standardization with AEHCh and BCh, respectively. The latter method shortened the total analysis time by about 15%, thus being especially suitable for continuous long-lasting off-line or on-line monitoring. Additionally, other endogenous cholines such as butyrylcholine or synthetic choline derivatives could be detected by the present method.

Acetylcholine↗
PubMed1998

Differential effects of selective adenosine A1 and A2A receptor agonists on dopamine receptor agonist-induced behavioural responses in rats.

The effects of the systemic (i.p.) administration of the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the selective adenosine A2A receptor agonist sodium 2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine (CGS 21680) on different dopamine receptor agonist-induced behaviours were studied in the male rat. CGS 21680 (1 micromol/kg), but not CPA, was found to counteract the stereotypies induced by the non-selective dopamine receptor agonist apomorphine (0.25 mg/kg s.c.). Low doses of CGS 21680 (0.1 micromol/kg) and high doses of CPA (3 micromol/kg) counteracted yawning induced by the dopamine D2 selective agonist quinpirole (0.05 mg/kg). On the other hand, low doses of CPA (0.3 micromol/kg) antagonized grooming induced by the selective dopamine D1 receptor-selective agonist SKF 38393 (10 mg/kg i.p.), while CGS 21680 was ineffective. These results are consistent with the proposed existence of a selective antagonistic modulation of dopamine D1 and D2 receptors by adenosine A1 and A2A receptors, respectively. The ability of CGS 21680 to counteract apomorphine-induced stereotypies is weaker compared to its previously reported antagonistic effect of amphetamine-induced motor activity. This supports the hypothesis that adenosine A2A receptor agonists may be potential antipsychotic drugs with a low potential for extrapyramidal side effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗