OBJECTIVE: Genetic and environmental factors interact in the development of major depressive disorder (MDD). While neurobiological correlates have only partially been elucidated, altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in animal models and in the cerebrospinal fluid of depressed patients were reported, suggesting that CGRP may be involved in the pathophysiology and/or be a trait marker of MDD. However, changes in CGRP brain levels resulting from interactions between genetic and environmental risk factors and the response to antidepressant treatment have not been explored. METHODS: We therefore superimposed maternal separation (MS) onto a genetic rat model (Flinders-sensitive and -resistant lines, FSL/FRL) of depression, treated these rats with antidepressants (escitalopram and nortriptyline) and measured CGRP-LI in selected brain regions. RESULTS: CGRP was elevated in the frontal cortex, hippocampus and amygdala (but not in the hypothalamus) of FSL rats. However, MS did not significantly alter levels of this peptide. Likewise, there were no significant interactions between the genetic and environmental factors. Most importantly, neither escitalopram nor nortriptyline significantly altered brain CGRP levels. CONCLUSION: Our data demonstrate that increased brain levels of CGRP are present in a well-established rat model of depression. Given that antidepressants have virtually no effect on the brain level of this peptide, our study indicates that further research is needed to evaluate the functional role of CGRP in the FSL model for depression.
- MeSH
- amygdala účinky léků metabolismus MeSH
- antidepresiva farmakologie MeSH
- čelní lalok účinky léků metabolismus MeSH
- citalopram farmakologie MeSH
- deprese * farmakoterapie etiologie metabolismus MeSH
- hipokampus účinky léků metabolismus MeSH
- interakce genů a prostředí * MeSH
- krysa rodu rattus MeSH
- maternální deprivace * MeSH
- modely nemocí na zvířatech MeSH
- mozek * účinky léků metabolismus MeSH
- nortriptylin farmakologie MeSH
- peptid spojený s genem pro kalcitonin * účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
There is a growing body of evidence that stressful events may affect the brain not only as a whole, but also in multiple laterality aspects. The present review is aimed at discussing the effect of stress and stress hormones on structural brain asymmetry. Differences and crossroads of functional and structural asymmetry are briefly mentioned throughout the document. The first part of this review summarizes major findings in the field of structural brain asymmetries in animals and humans from the evolutionary perspective. Additionally, effect of stress on animals is discussed generally. The second part then explores asymmetrical effects of stress on structural changes of principal brain areas - amygdala, hippocampus, neocortex, diencephalon, basal forebrain and basal ganglia from the point of normal lateralization, steroids, trauma and genetic factors. At the end we present hypothesis why stress appears to have asymmetrical effects on lateralized brain structures.
- MeSH
- amygdala diagnostické zobrazování metabolismus MeSH
- bazální ganglia diagnostické zobrazování metabolismus MeSH
- biologická evoluce MeSH
- diencefalon diagnostické zobrazování metabolismus MeSH
- funkční lateralita MeSH
- glukokortikoidy metabolismus MeSH
- hipokampus diagnostické zobrazování metabolismus MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek diagnostické zobrazování metabolismus MeSH
- neokortex diagnostické zobrazování metabolismus MeSH
- pars basalis telencephali diagnostické zobrazování metabolismus MeSH
- posttraumatická stresová porucha diagnostické zobrazování MeSH
- psychický stres metabolismus MeSH
- systém hypofýza - nadledviny metabolismus MeSH
- systém hypotalamus-hypofýza metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The aim of the present work was to study the influence of variable stress on the expression of 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) and the neuropeptides corticotropin-releasing hormone (CRH), urocortins 2 and 3(UCN2, UCN3), arginine vasopressin (AVP), oxytocin (OXT) and adenylate cyclase-activating polypeptide (PACAP) in two inbred rat strains: stress hypo-responsive Lewis (LEW) and hyper-responsive Fisher 344 (F344) rats. We found site-specific and strain-dependent differences in the basal and stress-stimulated expression of 11HSD1, CRH, UCN2, UCN3 and PACAP. In LEW rats, stress upregulated 11HSD1 in the prefrontal cortex and lateral amygdala, whereas in F344 rats 11HSD1 was upregulated in the central amygdala and hippocampal CA2 and ventral but not dorsal CA1 region; no effect was observed in the paraventricular nucleus, pituitary gland and adrenal cortex of both strains. The expression of glucocorticoid receptors did not parallel the upregulation of 11HSD1. Stress also stimulated the expression of paraventricular OXT, CRH, UCN3 and PACAP in both strains but amygdalar CRH only in LEW and UCN2/UCN3 in F344 rats, respectively. The upregulation of PACAP and CRH was paralleled only by increased expression of PACAP receptor PAC1 but not CRH receptor type 1. These observations provide evidence that inbred F344 and LEW rats exhibit not only the well-known phenotypic differences in the activity of the HPA axis but also strain- and stress-dependent differences in the expression of genes encoding 11HSD1 and neuropeptides associated with the HPA axis activity. Moreover, the differences in 11HSD1 expression suggest different local concentration of corticosterone and access to GR in canonical and noncanonical structures of the HPA axis.
- MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika metabolismus MeSH
- amygdala metabolismus MeSH
- arginin vasopresin genetika metabolismus MeSH
- hipokampus metabolismus MeSH
- hormon uvolňující kortikotropin genetika metabolismus MeSH
- hypofýza metabolismus MeSH
- hypofyzární adenylátcyklázu aktivující peptid genetika metabolismus MeSH
- krysa rodu rattus MeSH
- kůra nadledvin metabolismus MeSH
- messenger RNA metabolismus MeSH
- mozek metabolismus MeSH
- nucleus paraventricularis hypothalami metabolismus MeSH
- oxytocin genetika metabolismus MeSH
- potkani inbrední F344 MeSH
- potkani inbrední LEW MeSH
- prefrontální mozková kůra metabolismus MeSH
- psychický stres genetika metabolismus MeSH
- receptory glukokortikoidů genetika metabolismus MeSH
- stanovení celkové genové exprese MeSH
- systém hypofýza - nadledviny metabolismus MeSH
- systém hypotalamus-hypofýza metabolismus MeSH
- urokortiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
The negative affective state of opiate abstinence plays an important role in craving and relapse to compulsive drug use. The dopamine system participates in the reward effects of opiate use and the aversive effect of opiate abstinence. The amygdala is an essential neural substrate for associative learning of emotion. To establish a model of conditioned place aversion (CPA) in morphine-treated rats, we used different visual and tactual cues as conditioned stimuli (CS) within a conditioning apparatus. An injection of naloxone served as the unconditioned stimulus (US). The 6-hydroxydopamine (6-OHDA) lesion technique was used to investigate the effects of the dopaminergic system of the central nucleus of the amygdala (CeA) on naloxone-induced CPA. Rats were rendered physically dependent via administration of increasing doses of morphine delivered via intraperitoneal injection. Doses increased by 20 % each day for 14 days, starting from an initial dose of 6 mg/kg. All rats also received a low dose of naloxone (0.1 mg/kg) by injection 4 hours after morphine treatment on days 11 and 13 to induce CPA in a biased two-compartment conditioned place apparatus. Morphine-dependent rats with sham lesions were found to develop significant CPA after naloxone treatment. Bilateral 6-OHDA lesions of the CeA impaired the acquisition of CPA but had no effect on locomotor activity. These results suggest that the dopaminergic system of the CeA plays an important role in the negative affective state of opiate abstinence.
- MeSH
- amygdala účinky léků metabolismus MeSH
- buněčné jádro účinky léků MeSH
- dopamin metabolismus MeSH
- klasické podmiňování účinky léků MeSH
- krysa rodu rattus MeSH
- morfin aplikace a dávkování farmakologie MeSH
- narkotika aplikace a dávkování farmakologie MeSH
- oxidopamin aplikace a dávkování farmakologie MeSH
- potkani Sprague-Dawley MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The binding of [3H]SCH 23390 has been studied in various brain regions of male mice with the experience of repeated victory (winners) or defeat (losers) gained over 10 (T10) and 20 (T20) days of daily agonistic confrontations. In the frontal cortex, Bmax of [3H]SCH 23390 binding sites was found to be increased in T10 losers and decreased in T20 losers when compared to the control mice. In the striatum, T10 and T20 winners had reduced values of [3H]SCH 23390 binding sites than the ones in the control mice. The Kd was increased in the frontal cortex of T10 losers and T10 winners as well as in the amygdala of T20 losers. Reduced Kd values were found in the striatum of all experimental groups as well as in the amygdala of T20 winners. Thus, both specific changes relating to social behavior patterns and non-specific ones in [3H]SCH 23390 binding were found in the brain regions of mice after 10 and 20 days of intermale confrontations.
- MeSH
- agonistické chování MeSH
- amygdala metabolismus MeSH
- antagonisté dopaminu metabolismus MeSH
- bazální ganglia metabolismus MeSH
- benzazepiny metabolismus MeSH
- časové faktory MeSH
- čelní lalok metabolismus MeSH
- chování zvířat MeSH
- financování organizované MeSH
- mozek metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- radioligandová zkouška MeSH
- receptory dopaminu D1 metabolismus MeSH
- sociální dominance MeSH
- tritium MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
OBJECTIVES: Minimally invasive procedures for treating temporal lobe epilepsy have been investigated recently, namely stereotactic and gamma knife amygdalohippocampectomy (AHE). However, the results are not fully satisfactory. Our aim was to evaluate efficacy and side-effects of stereotactic AHE mimicking the neurosurgical procedure in terms of extent of the lesion. METHODS: 16 consecutive patients were assessed using VEEG, MRI, FDG-PET and WADA test. All had definite pharmacoresistant medial temporal lobe epilepsy. The stereotactic AHE was performed on the Leksell stereotactic system. All lesions exceeded 40 mm along the long axis of the hippocamus. RESULTS: Seizure outcome was favourable on one year follow-up: 12 patients (75%) were seizure-free (Engel I), three (19%) were Engel II, and one (6%) was Engel III. Side-effects were mild, lasting up to 7 days: cephalea, meningeal syndrome with sterile CSF in three subjects, and CSF leak lasting up to 3 days in seven subjects. CONCLUSION: Stereotactic AHE encompassing sufficient volume of the amygdalohippocampal complex appears to be safe, effective, and free from long-term side-effects.
- MeSH
- amygdala chirurgie metabolismus patologie MeSH
- dospělí MeSH
- epilepsie temporálního laloku chirurgie metabolismus patologie MeSH
- financování organizované MeSH
- fluorodeoxyglukosa F18 diagnostické užití MeSH
- hipokampus chirurgie metabolismus patologie MeSH
- léková rezistence MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- neurochirurgické výkony MeSH
- pozitronová emisní tomografie MeSH
- radiofarmaka diagnostické užití MeSH
- stereotaktické techniky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH