Biomedical subjects

S O Ogren

Publications and source records attributed to S O Ogren.

At least 55 records · Page 3Linked to original sources

PubMed1998

Dopamine D1 and D2 receptor-mediated acute and long-lasting behavioral effects of glial cell line-derived neurotrophic factor administered into the striatum.

To determine the differences in behavioral effects between intrastriatal and intracerebroventricular glial cell-derived neurotrophic factor (GDNF) administration, spontaneous locomotor activity was measured after intrastriatal or intracerebroventricular injection of GDNF (10 microg) in normal adult rats with implanted guide cannulae. In addition, the distribution of GDNF after intracerebral injection was studied immunohistochemically. Intrastriatal administration of GDNF significantly increased rearing behavior 3-4 h after injection. Increases in all three aspects of locomotor activity (motility, locomotion, and rearing) were most pronounced 3 days after intrastriatal injection, and they lasted for several days. This hyperactivity was blocked by the selective dopamine D1 receptor antagonist SCH22390 and by the selective D2 receptor antagonist raclopride at doses of the dopamine receptor antagonists, which by themselves did not affect spontaneous locomotor activity. These results suggest that GDNF has both acute and long-lasting pharmacological effects on dopamine neurons in adult animals and stimulates locomotor activity by activating both dopamine D1 and D2 receptors. On the other hand, intracerebroventricular administration of the same dose of GDNF failed to increase locomotor activity at any time during the test period (12 days). The immunohistochemical study demonstrated widespread distribution of GDNF in the entire body of the striatum within 24 h after intrastriatal injection. It also revealed deep penetration of GDNF from the ventricular space into the brain parenchyma after intracerebroventricular injection. GDNF-immunoreactive neuronal cell bodies were seen in the ipsilateral substantia nigra pars compacta most frequently 6 h after intrastriatal injection. The number of such cell bodies after intracerebroventricular administration, on the other hand, was much lower than that seen after intrastriatal administration. Taken together, these data suggest that intrastriatal administration of GDNF is an effective approach for affecting DA transmission. Long-lasting behavior effects are mediated via dopamine D1 and D2 receptors. Higher doses of GDNF would probably be needed using the intracerebroventricular route as compared to intraparenchymal delivery to exert effects on the nigrostriatal system in Parkinson's disease patients.

Animals↗

PubMed1998

Modulation of motor behaviour by NMDA- and cholecystokinin-antagonism.

Motor behaviour relies on complex neurochemical interactions in the basal ganglia, in particular the striatum. Antagonistic influences in this region are exerted by afferent projections from, on the one hand, the ventral mesencephalon, utilizing dopamine as a transmitter, and, on the other hand, from the cerebral cortex, signalling by the excitatory amino acid glutamate. The activity in both these neuronal populations appears to be regulated by the neuropeptide cholecystokinin. This article concentrates on interactions between cholecystokinin and glutamate, summarizing some recent morphological, biochemical and behavioural findings. It is suggested that cholecystokinin, acting via the cholecystokininB receptor, potentiates the glutamatergic excitatory input to the striatum.

Animals↗

PubMed1998

Distribution and kinetics of galanin infused into the ventral hippocampus of the rat: relationship to spatial learning.

A recent study has shown that ventral hippocampal galanin plays a role in spatial learning and that it has an inhibitory effect on basal acetylcholine release [Ogren S. O. et al. (1996) Neuroscience 75, 1127-1140]. The present studies were designed to compare the in vivo tissue distribution and kinetics of infused galanin (porcine) with the temporal effect of galanin on spatial learning in the rat. Daily bilateral microinfusions of galanin (1.5 nmol/side for five days) via chronic cannulae placed in the ventral hippocampus produced a significant impairment of acquisition of the spatial task when infused 20 min, but not 5 or 60 min, before the daily training session. No overall impairment of memory retention (examined 24 h after the last training session) was observed in the galanin-treated rats. These results indicate that galanin given in the ventral hippocampus produces a time-dependent effect on acquisition. Using an antibody to porcine galanin and immunohistochemistry, galanin infused in the ventral hippocampus was found to be distributed mainly within the ventral part of the hippocampus and around the infusion site. The infused galanin was rapidly cleared from the extracellular space between 5 and 20 min after infusion. Five minutes after infusion of galanin, a number of cells in the ventral hippocampus, both within and outside the zone of extracellularly located galanin, showed a positive galanin-like immunoreactivity. These cells appear morphologically to be medium-sized neurons with a similar position as cells showing neuropeptide Y-like immunoreactivity. At 20 and 60 min after infusion of galanin, no cells with detectable levels of galanin-like immunoreactivity could be seen. These results indicate that the temporal kinetics and distribution of infused galanin are of major importance for its behavioural effect in the ventral hippocampus. The rapid clearance of the infused galanin and its internalization by neuronal endocytotic mechanisms may be important for its effect on cognition.

Animals↗

PubMed1998

Hippocampal dynorphin B injections impair spatial learning in rats: a kappa-opioid receptor-mediated effect.

The hippocampus plays a central role in the acquisition and storage of information. Long-term potentiation in the mossy fibre pathway to the CA3 region in the hippocampus, an animal model of memory acquisition, is modulated by dynorphin peptides. This study investigated the possible role of hippocampal dynorphin in spatial learning. Male rats were trained in the Morris Water Task after microinjection with different doses of dynorphin B (1, 3.3 or 10 nmol/rat) or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal hippocampus. Dynorphin B was found to impair spatial learning at all tested doses. The synthetic kappa1-selective opiate receptor antagonist nor-binaltorphimine (2 nmol) also given into the hippocampus fully blocked the acquisition impairment caused by dynorphin B (10 nmol), while nor-binaltorphimine alone did not affect learning performance. These findings suggest that dynorphin peptides could play a modulatory role in hippocampal plasticity by acting on hippocampal kappa-receptors and thereby impair spatial learning.

Animals↗

PubMed1998

"Atypical" neuromodulatory profile of glutapyrone, a representative of a novel 'class' of amino acid-containing dipeptide-mimicking 1,4-dihydropyridine (DHP) compounds: in vitro and in vivo studies.

Glutapyrone, a disodium salt of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)- glutaric acid, is a representative of a novel 'class' of amino acid-containing 1,4-dihydropyridine (DHP) compounds developed at the Latvian Institute of Organic Synthesis, Riga, Latvia. Conceptually, the glutapyrone molecule can be regarded as a dipeptide-mimicking structure formed by the "free" amino acid (glutamate) moiety and "crypto" (built into the DHP cycle) amino acid ("GABA") elements. Both of these amino acids are joined by the peptide bond. This compound unlike classical DHPs lacks calcium antagonistic or agonistic properties. Our previous studies revealed a profound and long-term anticonvulsant, stress-protective and neurodeficit-preventive activities of glutapyrone. In view of structural properties the role of glutamatergic mechanisms in the mediation of central effects of glutapyrone was considered. In the present study glutapyrone at the concentration range of 1 microM(-1) mM failed to effect both NMDA ([3H]TCP) and non-NMDA ([3H]KA and [3H]AMPA) receptor ligand binding in the rat cortical membranes in vitro. The compound markedly enhanced motor hyperactivity induced by the NMDA antagonist PCP and the dopamine releasing compound D-amphetamine in the rats. Glutapyrone displayed activity in a variety of animal models relevant for affective/depressive disorders in humans i.e. reserpine-induced ptosis and hypothermia, forced swimming test and open field test. These data indicate that the unusually "broad" pharmacological spectrum of glutapyrone might involve concomitant actions on multiple neurotransmitter systems, particularly, GABA-ergic and the catecholamines. It is discussed whether these functional properties are secondary to action on intracellular events, predominantly, G protein-related since glutapyrone appears to lack direct interactions with a number of receptors including ionotropic glutamate and GABA(A)/Bzd receptors.

Analysis of Variance↗

PubMed1998

Animal models for studying serotonin (5-HT) receptor subtypes: relationship to 5-HT system pathologies.

Despite more than 30 years of intensive research, the specific role of serotonin (5-HT) receptor subtypes in animal models of "anxiety" still remains unclear. The present study focused on the particular role of 5-HT1A receptor subtype in aversive learning, i.e., the passive avoidance (PA) task in the rat. Taken together, the data strongly suggest that: (1) 5-HT1A receptor but not 5-HT2A receptors play a crucial role in PA; (2) the postsynaptic but not presynaptic 5-HT1A receptors are mainly involved in the regulation of PA; (3) 5-HT1A receptors appear to be directly involved both in acquisition and retrieval but not in the consolidation of PA; and (4) besides the "prototypical" 5-HT1A receptor subtype, an additional and yet-unidentified 5-HT receptor subtype seems to play an important modulatory role in PA.

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

PubMed1998

Analysis of the 5-HT1A receptor involvement in passive avoidance in the rat.

1. The effects of the 5-HT2A/2C agonist DOB, the selective 5-HT1A agonist NDO 008 (3-dipropylamino-5-hydroxychroman), and the two enantiomers of the selective 5-HT1A agonist 8-OH-DPAT (R(+)-8-OH-DPAT and S(-)-8-OH-DPAT) were studied in a step-through passive avoidance (PA) test in the male rat. 2. The 5-HT1A agonists injected prior to training (conditioning) produced a dose-dependent impairment of PA retention when examined 24 h later. R(+)-8-OH-DPAT was four times more effective than S(-)-8-OH-DPAT to cause an impairment of PA retention. Both NDO 008 and the two enantiomers of 8-OH-DPAT induced the serotonin syndrome at the dose range that produced inhibition of the PA response, thus, indicating activation of postsynaptic 5-HT1A receptors. 3. Neither NDO 008 nor R(+)-8-OH-DPAT induced head-twitches, a behavioural response attributed to stimulation of postsynaptic 5-HT2A receptors. In contrast, DOB induced head-twitches at the 0.01 mg kg(-1) dose while a 200 times higher dose was required to produce a significant impairment of PA retention. 4. The impairment of PA retention induced by both NDO 008 and R(+)-8-OH-DPAT was fully blocked by the active S(+)- enantiomer of the selective 5-HT1A antagonist WAY 100135 and the mixed 5-HT1A/beta-adrenoceptor antagonist L(-)-alprenolol. In contrast, the mixed 5-HT2A/2C antagonists ketanserin and pirenperone were found to be ineffective. Moreover, the beta2-adrenoceptor antagonist ICI 118551, the beta-antagonist metoprolol as well as the mixed beta-adrenoceptor blocker D(+)-alprenolol all failed to modify the deficit of PA retention by NDO 008 and R(+)-8-OH-DPAT. None of the 5-HT1A or 5-HT2A/2C receptor antagonists tested or the beta-blockers altered PA retention by themselves. 5. A 3 day pretreatment procedure (200+100+100 mg kg(-1)) with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) did not alter PA retention and did not prevent the inhibitory action of the 5-HT1A agonists, indicating that their effects on PA do not depend on endogenous 5-HT. 6. The effects of NDO 008 on PA were also studied using a state-dependent learning paradigm. NDO 008 was found to produce a disruption of PA when given either prior to training or retention or both prior to training and retention but it failed to affect PA retention when given immediately after training. .7 These findings indicate that the deficit of passive avoidance retention induced by the 5-HT1A agonists is mainly a result of stimulation of postsynaptic 5-HT1A receptors but not 5-HT2A receptors. The 5-HT1A receptor stimulation appears to interfere with learning processes operating at both acquisition and retrieval.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1998

Estrogen down-regulates mRNA encoding the exocytotic protein SNAP-25 in the rat pituitary gland.

Exocytosis is dependent on specific proteins that are located at the secretory granule membrane, in the cytoplasm or at the plasma membrane. The mRNA expression of synaptosomal-associated protein of 25 kDa (SNAP-25) isoforms SNAP-25a and SNAP-25b, vesicle associated membrane protein (VAMP) 2, mammalian homologue of unc-18 (munc-18) and Hrs-2 was studied in the pituitary of ovariectomized rats after subcutaneous insertion of capsules containing estrogen or placebo using in situ hybridization. Estrogen treatment (0.25 mg estradiol) significantly decreased SNAP-25a (32%; 10%) and SNAP-25b (25%; 22%) mRNA levels in the anterior and intermediate lobes, respectively, whereas VAMP-2, munc-18 and Hrs-2 mRNA levels remained unchanged. The results suggest that estrogen selectively regulates SNAP-25 transcription in the pituitary gland, but leaves VAMP-2, munc-18 and Hrs-2 mRNA levels unaffected.

Adenosine Triphosphatases↗

PubMed1998

Intraventricular galanin modulates a 5-HT1A receptor-mediated behavioural response in the rat.

The present studies have examined whether the neuropeptide galanin can modulate brain serotoninergic (5-HT) neurotransmission in vivo and, particularly, 5-HT1A receptor-mediated transmission. For that purpose, we studied the ability of galanin (given bilaterally into the lateral ventricle, i.c.v.) to modify the impairment of passive avoidance retention induced by the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propyloamino)tetralin (8-OH-DPAT) when injected prior to training. This impairment appears to be mainly related to activation of 5-HT1A receptors in the CNS. Galanin dose-dependently (significant at 3.0 nmol/rat) attenuated the passive avoidance impairment (examined 24 h after training) induced by the 0.2 mg/kg dose of 8-OH-DPAT. This 8-OH-DPAT dose produced signs of the 5-HT syndrome indicating a postsynaptic 5-HT1A receptor activation. Furthermore, both the impairment of passive avoidance and the 5-HT syndrome were completely blocked by the 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg). Galanin (0.3 or 3.0 nmol) or WAY 100635 (0.1 mg/kg) failed by themselves to affect passive avoidance retention. 8-OH-DPAT given at a low dose 0.03 mg/kg, which presumably stimulates somatodendritic 5-HT1A autoreceptors in vivo, did not alter passive avoidance retention or induce any visually detectable signs of the 5-HT syndrome. Galanin (0.3 or 3.0 nmol) given i.c.v. in combination with the 0.03 mg/kg dose of 8-OH-DPAT, did not modify passive avoidance. The immunohistochemical study of the distribution of i.c.v. administered galanin (10 min after infusion) showed a strong diffuse labelling in the periventricular zone (100-200 microm) of the lateral ventricle. Furthermore, in the dorsal and ventral hippocampus galanin-immunoreactive nerve cells appeared both in the dentate gyrus and the CA1, CA2 and CA3 layers of the hippocampus. In the septum only endogenous fibres could be seen while in the caudal amygdala also galanin-immunoreactive nerve cells were visualized far away from the labelled periventricular zone. At the level of the dorsal raphe nucleus a thin periventricular zone of galanin immunoreactivity was seen but no labelling of cells. These results suggest that galanin can modulate postsynaptic 5-HT1A receptor transmission in vivo in discrete cell populations in forebrain regions such as the dorsal and ventral hippocampus and parts of the amygdala. The indication that galanin administered intracerebroventrically may be taken up in certain populations of nerve terminals in the periventricular zone for retrograde transport suggests that this peptide may also affect intracellular events.

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

PubMed1997

5-HT1A receptor activation: short-term effects on the mRNA expression of the 5-HT1A receptor and galanin in the raphe nuclei.

Systemic administration of the 5-HT1A receptor agonist 8-OH-2-(di-n-propylamino)-tetralin (8-OH-DPAT; 0.3 mg/kg, s.c.) was used to explore the effects of activation of 5-HT1A receptors on expression of mRNA coding for 5-HT1A receptor, tryptophan hydroxylase (TPH) and galanin in the ascending raphe nuclei. 8-OH-DPAT increased the hybridization signal of the 5-HT1A receptor by 105% in the dorsal raphe nucleus (B7) 30 min after the injection. No effects were seen at the later time points (2-8 h). In the median raphe nucleus (B8) and the B9 cell group in the medial lemniscus, 8-OH-DPAT induced a marked decrease in labeling 30 min after injection. At 8 h following 8-OH-DPAT injection, the effect had shifted to an increase in 5-HT1A receptor labeling by 68% in the B8 area. Importantly 8-OH-DPAT had no significant effects on the expression of mRNA coding for TPH and galanin. The results suggest an important and differential mechanism for the regulation of 5-HT1A receptor mRNA levels in the dorsal and median raphe nuclei. This regulation may be of importance for the differential control of the activity of the ascending 5-HT neurons, and hence for mood regulation. The results also indicate a dissociation between the effects mediated by 5-HT1A receptor functions and those regulating the coexisting peptide galanin in the dorsal raphe.

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

PubMed1997

Prolonged treatment with haloperidol and clozapine in the rat: differential effects on spontaneous and theophylline-induced motor activity.

Difference in striatal dopamine D2 receptors and in spontaneous and theophylline-induced motor activity in rats withdrawn (for 72 h) from prolonged treatment with haloperidol or clozapine were studied. Haloperidol but not clozapine pretreatment increased the binding of the dopamine D2 antagonist [3H]raclopride in striatal membrane preparations, due to an increased number of striatal dopamine D2 receptors (Bmax) without changes in affinity (Kd). Haloperidol induced a significant increase (in motility and locomotion) and clozapine a decrease (in locomotion) of the spontaneous motor activity. Haloperidol but not clozapine pretreatment was associated with a stronger theophylline-induced motor activation. These results suggest that prolonged treatment with typical but not with atypical antipsychotics are associated with adaptive changes at both dopamine and adenosine receptors.

Animals↗

PubMed1997

Dopamine receptor antagonists block nerve growth factor-induced hyperactivity.

The role of dopamine receptors in mediating nerve growth factor (NGF)-induced locomotor stimulation was investigated by examining the effects of selective dopamine D1 and D2 receptor antagonists on the motor hyperactivity induced by NGF. A single intracerebroventricular administration of NGF (5.1 microg) increased locomotor activity immediately after injection in normal adult rats. This hyperactivity was partly blocked by the dopamine D1 receptor antagonist SCH23390 (R-(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepine-8- ol) and by the dopamine D2 antagonist raclopride ((S)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-6-methoxy benzamide). Effective doses of raclopride did not alter spontaneous levels of activity in control rats. These results suggest that stimulation of both subtypes of dopamine receptors is necessary for eliciting NGF-induced hyperactivity in the rat. The role of the dopamine D2 receptor in mediating the behavioral actions of NGF appears to be more important than that of the dopamine D1 receptor.

Animals↗

PubMed1997

Intraventricular injection of NGF, but not BDNF, induces rapid motor activation that is inhibited by nicotinic receptor antagonists.

The acute and subacute effects of intracerebroventricularly (ICV) administered nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) on locomotor activity were evaluated in awake adult rats. Immediately after ICV injection through an implanted cannula, locomotor activity was measured by a computerized system using infrared photocells, which allowed us to record locomotion, motility, and rearing simultaneously. A single dose of 5 microg mouse beta-NGF produced significant increases in horizontal ambulatory components of locomotor activity (locomotion and motility), but not vertical movement (rearing) 30-45 min after ICV administration. These increases lasted for at least 3-4 h. Systemic injection of 2.0 mg/kg mecamylamine, a central nicotinic receptor antagonist, inhibited the hyperactivity induced by NGF. Systemic injection of 0.5 mg/kg scopolamine, a muscarinic receptor antagonist, did not interfere with the NGF effects. Thus, while scopolamine induced marked increases in all three measures of behavior in both NGF and cytochrome-c-treated animals, locomotion and motility remained significantly higher in the NGF group. Immunohistochemistry demonstrated that NGF diffused readily from the ventricular space into brain parenchyma on the injected side and could be visualized 1 h after ICV injection. These results suggest that ICV administration of NGF increases locomotor activity by inducing acetylcholine release, and that nicotinic receptors are involved in the hyperactivity induced by NGF. ICV administration of 5 microg recombinant human BDNF had no significant effect on locomotor activity during the 0- to 4-h period after ICV injection. However, it produced significant decreases in locomotion, motility, and rearing 24-26 h later. Hence ICV administration of BDNF has entirely different effects on animal behavior from those evoked by NGF. While NGF elicits increases in ambulatory behavior within hours, BDNF causes delayed decreases in ambulatory behavior.

Animals↗

PubMed1997

Prenatal exposure to methylmercury alters locomotor activity of male but not female rats.

In the present study the neurotoxic effects of a low dosage (0.5 mg/kg per day) of methylmercury (MeHg) on the developing nervous system were investigated. Pregnant rats were treated with MeHg from day 7 of pregnancy to day 7 of lactation. Locomotor activity (locomotion, rearing, and motility) and spatial learning ability were tested in the offspring at 6 months of age. The expression of tyrosine hydroxylase (TH) was examined by immunohistochemistry and in situ hybridization. A significant decrease in spontaneous motility and rearing was observed only in the MeHg-treated male rats. After administration of a low dose of d-amphetamine (0.5 mg/kg) no differences could be observed between control and MeHg-treated male rats, suggesting that changes in dopaminergic transmission were involved. However, no change in TH messenger RNA expression was observed. No changes in spatial learning acquisition or memory were shown in MeHg-treated rats. Taken together, these findings show that during development a very low dosage of MeHg exerts neurotoxic effects detectable in adulthood, and that susceptibility is gender-dependent.

Animals↗

PubMed1997

Cholecystokinin B receptor antagonists enhance the locomotor response to the N-methyl-D-aspartate antagonists phencyclidine and dizocilpine maleate.

The cholecystokinin antagonists L-740,093, L-365,260, LY-288513 and CI988, which are all selective for the cholecystokininB receptor subtype, were examined for their ability to modulate locomotor activity induced by the non-competitive N-methyl-D-aspartate receptor antagonists phencyclidine and dizocilpine maleate (MK-801) in habituated rats. It was found that the locomotor effects (motility, locomotion) produced by subcutaneous administration of phencyclidine (2 mg/kg) were significantly potentiated by intraperitoneal (i.p.) administration of L-740,093 (1 mg/kg), L-365,260 (10 mg/kg), LY-288513 (10 mg/kg), but not CI-988 (10 mg/kg). Locomotor activity induced by subcutaneous administration of MK-801 (0.15 mg/kg) was potentiated by intraperitoneal L-740,093 (0.3, 1 and 3 mg/kg). L-740,093, L-365,260, LY-288513 and CI-988 administered alone did not alter spontaneous locomotor activity (motility) as compared to vehicle/saline controls. However, when these antagonists were administered to naive, unhabituated rats, L-365,260 and LY-288513 caused a significant reduction in motility compared to the vehicle control. These findings suggest that, although cholecystokinin may be involved in exploratory behaviour exhibited by rats in a novel environment (unhabituated rats), its role is negligible in rats subjected to a familiar environment (habituated rats). Furthermore, these results support the interpretation that cholecystokinin has a suppressant effect on locomotion elicited by phencyclidine and MK-801, and that this inhibitory action of cholecystokinin is mediated via the cholecystokininB receptor, since it can be eliminated by administration of cholecystokininB antagonists. It is suggested that the site of action of the cholecystokininB receptors involves mainly the cholecystokinin/glutamate projection from the cortex to the anterior nucleus accumbens and/or striatum. Finally, the present study provides two examples of endogenous release of a neuropeptide resulting in behavioural consequences.

Animals↗

PubMed1997

Prenatal corticosterone treatment induces long-term changes in spontaneous and apomorphine-mediated motor activity in male and female rats.

The potential influence of glucocorticoids on fetal brain development was investigated after corticosterone administration via pellets to pregnant rats during the last trimester of gestation. We examined both spontaneous motor activity and dopamine-mediated motor responses to apomorphine, a D1, D2 and D3 receptor agonist, given at a postsynaptic dose (1 mg/kg, s.c.) to both prepubertal and adult male and female offspring. Prenatal corticosterone was found to produce the following alterations in the offspring. (1) Prepubertal stage: Male offspring: a statistically significant (P < 0.05) increase was observed in spontaneous rearing, motility and locomotion (activity measured during the first 30 min) without changes in apomorphine-induced motor responses. Female offspring: a reduction (P < 0.05) only in spontaneous rearing activity was observed during the exploratory phase (activity measured during the first 10 min) without significant changes in apomorphine-induced motor responses. (2) Adult stage: Male offspring: the exploratory activity to the novel environment was increased (P < 0.05) without significant changes in apomorphine-induced motor activity. Female offspring: an increase (P < 0.05) in spontaneous locomotion was observed during the first 30 min of testing without significant changes in exploratory activity to the novel environment. However, the apomorphine-induced motility and locomotion were reduced (P < 0.05) during the first 30 min. These observations indicate that prenatal corticosterone induces both short-term and long-term changes in spontaneous motor activity as well as long-lasting alterations in dopamine receptor response in the motor network mechanisms controlled by DA receptors. These changes are in part age and sex-dependent. The possible relationship between prenatal programming of the mesolimbic and nigrostriatal dopaminergic pathways by corticosterone and the observed changes in motor function is discussed.

Animals↗

PubMed1997

Adenosine A2A agonists: a potential new type of atypical antipsychotic.

The systemic intraperitoneal (i.p.) administration of the adenosine A2A agonist CGS 21680 was found to dose-dependently antagonize spontaneous and amphetamine-induced (1 mg/kg i.p.) motor activity with similar ED50 values (about 0.2 mg/kg). The ratios between the ED50 values for induction of catalepsy and for antagonizing amphetamine-induced motor activity for CGS 21680, haloperidol, and clozapine were 12, 2, and > 30, respectively. Furthermore, CGS 21680 was comparably much stronger than haloperidol or clozapine at antagonizing the motor activity induced by phencyclidine (2 mg/kg subcutaneously) than motor activity induced by amphetamine (1 mg/kg i.p.). In conclusion, the present results show a clear "atypical" antipsychotic profile of the adenosine A2A agonist CGS 21680 in animal models.

Adenosine↗

PubMed1997

Differential effects of the neuropeptide galanin on striatal acetylcholine release in anaesthetized and awake rats.

1. In the present study the mechanisms were examined by which the neuropeptide galanin modulates the extracellular concentrations of striatal acetylcholine (ACh) in enflurane anaesthetized and in freely moving male rats by use of in vivo microdialysis and high performance liquid chromatography. 2. The perfusion of galanin through the microdialysis probe (0.3 nmol microl(-1), flow rate: 2 microl min(-1)) caused a statistically significant increase in the basal striatal ACh levels in anaesthetized but a decrease in awake animals. No significant effect was revealed after a low dose (0.1 nmol microl(-1), flow rate: 2 microl min(-1)) of galanin perfusion. Both the stimulating and inhibitory effects of galanin on basal ACh release were reversible. 3. The muscarinic antagonist scopolamine (0.1 mg kg(-1), subcutaneously (s.c.)) caused a significant increase in ACh release in both anaesthetized and awake animals. 4. The combination of galanin plus scopolamine attenuated the stimulant effect on ACh release caused by scopolamine alone in awake animals. 5. The putative galanin receptor antagonist M35 at 0.3 nmol microl(-1) but not at 0.1 nmol microl(-1) caused a significant reduction (20%) in ACh release, supporting the view that M35 at higher concentrations behaves as a partial agonist at the galanin receptor. When M35 (0.1 nmol microl(-1)) was co-infused with galanin (0.3 nmol microl(-1)) the galanin-evoked decrease in ACh release was completely blocked. 6. Taken together, these results indicate that galanin affects basal ACh release via stimulation of galanin receptors within the striatum. The mechanism involved is dependent on the anaesthesia procedure which may act via enhancement of gamma-aminobutyric acidA (GABA(A)) mediated transmission within striatal and/or output neurones. In addition, anaesthesia may also decrease the activity of glutamatergic striatal afferents. The results with M35 indicate that the role of galanin perfused in striatum is permissive in the normal rat. Furthermore, galanin is a potent inhibitory modulator of basal ACh release also in the striatum, as recently was shown in the ventral hippocampus in awake animals.

Acetylcholine↗