Alterations of reward mechanisms in bulbectomised rats.

The positive association between alcoholism and depression is a common clinical observation. We investigated the relationship between depression and reward mechanisms using a validated animal model for depressive-like behaviour, the olfactory bulbectomy in rats. The effects of bilateral olfactory bulbectomy on reward mechanisms were studied in two different experimental paradigms - the voluntary self-administration of ethanol and the conditioned place preference to alcohol injection and compared to the effects of ethanol on locomotor activity and body core temperature.

Tolerance to LSD and DOB induced shaking behaviour: differential adaptations of frontocortical 5-HT(2A) and glutamate receptor binding sites.

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD) and dimethoxy-bromoamphetamine (DOB), provoke stereotype-like shaking behaviour in rodents, which is hypothesised to engage frontocortical glutamate receptor activation secondary to serotonin2A (5-HT2A) related glutamate release. Challenging this hypothesis, we here investigate whether tolerance to LSD and DOB correlates with frontocortical adaptations of 5-HT2A and/or overall-glutamate binding sites. LSD and DOB (0.

Hippocampus-dependent learning in SKAP-HOM deficient mice.

SKAP-HOM is an adapter protein which regulates the cross-talk between immunoreceptors and integrins and is involved in signal transduction. It is present in murine brain structures such as the hippocampus, frontal cortex, and cerebellum. In the present study we investigated types of hippocampus-dependent learning (fear conditioning, social memory, and the Morris Water Maze) and locomotor sensitization to amphetamine in transgenic SKAP-HOM deficient mice (-/-) in comparison with respective controls (+/+).

Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling.

A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.

Behavioral and neurochemical characterization of kratom (Mitragyna speciosa) extract.

Objective: Mitragyna speciosa and its extracts are named kratom (dried leaves, extract). It contains several alkaloids and is used in traditional medicine to alleviate musculoskeletal pain, hypertension, coughing, diarrhea, and as an opiate substitute for addicts. Abuse and addiction to kratom is described, and kratom has attracted increasing interest in Western countries.

Cannabinoid-mediated diversity of antinociceptive efficacy of parecoxib in Wistar and Sprague Dawley rats in the chronic constriction injury model of neuropathic pain.

We studied nociceptive behavior and the effects of analgesics in Wistar (Wist) and Sprague Dawley (SPD) rats and in CB1 receptor-deficient mice with neuropathic pain experimentally. Neuropathic pain was induced by loose ligation of the sciatic nerve (chronic constriction injury, CCI). In CCI rats from both strains, cold allodynia and a reduced thermal pain threshold were detected, whereas no effect was found in the hot plate test.

Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats.

Background: Vagus nerve stimulation (VNS) has been introduced as a therapeutic option for treatment-resistant depression. The neural and chemical mechanisms responsible for the effects of VNS are largely unclear.

Methods: Bilateral removal of the olfactory bulbs (OBX) is a validated animal model in depression research.

Analgesic tolerance to high-efficacy agonists but not to morphine is diminished in phosphorylation-deficient S375A μ-opioid receptor knock-in mice.

Morphine is one of the most potent analgesic drugs. However, the utility of morphine in the management of chronic pain is limited by its rapid development of tolerance. Morphine exerts all of its pharmacological effects via the μ-opioid receptor.

Evaluation of the effects of Astragalus mongholicus Bunge saponin extract on central nervous system functions.

Ethnopharmacological Relevance: In traditional medicine, Astragalus mongholicus (AM) has been used for the treatment of general weakness, chronic illness, and to increase overall vitality.

Aim Of The Study: The present study investigated possible effects of the saponin fraction of AM on the central nervous system. Moreover, its effects on locomotor activity, anxiety, and hippocampal morphology were studied.

Haloperidol normalized prenatal vitamin D depletion-induced reduction of hippocampal cell proliferation in adult rats.

Considering the fact that schizophrenia is a highly complex disorder of the human brain, different models are needed to test specific causative or mechanistic hypotheses. The pathogenesis of schizophrenia is also characterized by abnormal neuronal development. It was found that schizophrenia as well as antipsychotic treatment are accompanied by alterations in neuronal proliferation.

Transient prenatal vitamin D deficiency is associated with changes of synaptic plasticity in the dentate gyrus in adult rats.

Transient prenatal vitamin D deficiency is considered a neurodevelopmental animal model in schizophrenia research. Vitamin D deficiency in female rats causes morphological, cellular and molecular changes in the brain and alters behaviour and nerve growth factors expression in their offspring. Prenatal depleted animals showed a significant impairment of latent inhibition, a feature often associated with schizophrenia and of hole board habituation.

Risperidone and haloperidol promote survival of stem cells in the rat hippocampus.

Altered neuroplasticity contributes to the pathophysiology of schizophrenia. However, the idea that antipsychotics may act, at least in part, by normalizing neurogenesis has not been consistently supported. Our study seeks to determine whether hippocampal cell proliferation is altered in adult rats pretreated with ketamine, a validated model of schizophrenia, and whether chronic administration with neuroleptic drugs (haloperidol and risperidone) affect changes of cell genesis/survival.

Improved learning and memory in aged mice deficient in amyloid beta-degrading neutral endopeptidase.

Background: Neutral endopeptidase, also known as neprilysin and abbreviated NEP, is considered to be one of the key enzymes in initial human amyloid-beta (Abeta) degradation. The aim of our study was to explore the impact of NEP deficiency on the initial development of dementia-like symptoms in mice.

Methodology/principal Findings: We found that while endogenous Abeta concentrations were elevated in the brains of NEP-knockout mice at all investigated age groups, immunohistochemical analysis using monoclonal antibodies did not detect any Abeta deposits even in old NEP knockout mice.

Haloperidol and risperidone have specific effects on altered pain sensitivity in the ketamine model of schizophrenia.

Rationale: The ketamine (ket) model reflects features of schizophrenia as well as secondary symptoms such as altered pain sensitivity.

Objectives: In the present study, we investigated the effect of subchronic oral treatment with haloperidol (hal, 0.075 mg/kg) and risperidone (ris, 0.

Emotional and learning behaviour in mice overexpressing heat shock protein 70.

The effects of inducible heat shock protein 70 (HSP70) on emotional and learning behaviour as well as hippocampal long-term potentiation was investigated in transgenic HSP70 overexpressing mice. In active two-way avoidance learning (shuttle box) as well as spatial 8-arm radial maze learning, the HSP70 overexpressing mice showed diminished learning performance. In several tests there was no indication of differences in anxiety behaviour between transgenic mice and wild-type mice.

Expression of mRNA of neurotrophic factors and their receptors are significantly altered after subchronic ketamine treatment.

The neurotrophic factors play an important role in the maintenance of neurone viability and neuronal communication which are considered to be altered in schizophrenia. Subchronic application of ketamine (Ket) was found to be a useful model in schizophrenia research. To further validate this model the mRNA levels of neurotrophic factors NGF, NT-3, and BDNF and their receptors TrkA, TrkB, and TrkC, respectively, were measured in different brain areas in Ket-pretreated rats subchronically dosed with the atypical antipsychotic drug risperidone (Ris).

Impaired spatial memory and altered dendritic spine morphology in angiotensin II type 2 receptor-deficient mice.

Mental retardation is the most frequent cause of serious handicap in children and young adults. Mutations in the human angiotensin II type 2 receptor (AT2) have been implicated in X-linked forms of mental retardation. We here demonstrate that mice lacking the AT2 receptor gene are significantly impaired in their performance in a spatial memory task and in a one-way active avoidance task.

Beacon-like/ubiquitin-5-like immunoreactivity is highly expressed in human hypothalamus and increased in haloperidol-treated schizophrenics and a rat model of schizophrenia.

The beacon gene is involved in the regulation of energy metabolism, food intake, and obesity. We localized its gene product, beacon-/ubiquitin 5-like immunoreactivity in brains of normal-weight, non-psychotic individuals, adipose (BMI over 32), non-psychotic individuals, and haloperidol-treated schizophrenics. The protein was found to be highly expressed in many neurons of the paraventricular and supraoptic hypothalamic nuclei.

Phosphodiesterase inhibitors--are they potential neuroleptic drugs?

It was suggested that phosphodiesterase (PDE) inhibitors may be potential neuroleptic drugs with a low risk of extrapyramidal symptoms. In the study presented, we compared the effects of the neuroleptics, haloperidol, and risperidone and the PDE10A inhibitor papaverine as well as the PDE4 inhibitor rolipram on retrieval of conditioned avoidance responding in the pole-jumping task and on locomotor activity. After acute administration, the substances used reduced locomotor activity dose-dependently.

Pentylenetetrazol-kindling in mice overexpressing heat shock protein 70.

Kindling induced by the convulsant pentylenetetrazol (PTZ) is an accepted model of primary generalized epilepsy. Because seizures represent a strong distressing stimulus, stress-induced proteins such as heat shock proteins might counteract the pathology of increased neuronal excitation. Therefore, the aim of the present study was to determine whether PTZ kindling outcome parameters are influenced by heat shock protein 70 (Hsp70) overexpression in Hsp70 transgenic mice as compared to the respective wild-type mice.

Pentylenetetrazole kindling affects sleep in rats.

Purpose: The aim of the study was to define sleep disturbances in pentylenetetrazole (PTZ)-kindled rats and to explore the effects of the nootropic drug piracetam (Pir; 100 mg/kg) and the noncompetitive N-methyl-D-aspartate (NMDA)-antagonist MK-801 (0.3 mg/kg), which normalized learning performance in PTZ-kindled rats, on altered sleep parameters.

Methods: This is the first report showing a significant reduction in paradoxical sleep (PS) as a consequence of PTZ kindling.

Pain sensitivity is altered in animals after subchronic ketamine treatment.

Rationale: Clinical observations have shown that pain sensitivity is altered in some schizophrenic patients.

Objectives: To study alterations in pain sensitivity, the ketamine model in schizophrenia research was employed.

Materials And Methods: Rats were subchronically injected with the dissociative anaesthetic ketamine (Ket, ten injections of 30 mg/kg, one injection per day over a period of 10 days).

Transcriptional response to the neuroleptic-like compound Ampullosporin A in the rat ketamine model.

Psychotic disorders affecting up to 1% of the human population represent pathological changes to the metabolic homeostasis of the brain. Increasing evidence in the literature suggests complex biochemical and/or transcriptional alterations accompanying schizophrenia-like phenomena. Sub-chronic treatment with sub-anaesthetic doses of ketamine induces schizophrenia-related psychotic alterations that can be used as an animal model in the study of this disorder.

Development of tolerance and sensitization to different opioid agonists in rats.

Rationale: Despite numerous investigations, the mechanisms underlying the development of opioid tolerance are far from clear. However, several in vitro studies implicated a protective role of agonist-induced micro-opioid receptor endocytosis in the development of opioid tolerance. Moreover, we have recently demonstrated that the high-efficacy agonist etonitazene promotes rapid endocytosis of micro-opioid receptors, whereas the agonist morphine and the low-efficacy agonist buprenorphine fail to promote detectable receptor endocytosis in micro-opioid receptor expressing HEK293 cells.