Showing papers by "Jacob Raber published in 2005"
TL;DR: Whether the diverse phenotypic differences observed in mGluR8–/– mice result from the misregulation of a unique neural pathway, possibly in the thalamus or hypothalamus, or whether they are the consequence of multiple developmental and functional alterations in synaptic transmission, remains to be determined.
Abstract: To study the role of the metabotropic glutamate receptor 8 (mGluR8), mice lacking this receptor were generated by homologous recombination. Homozygous mGluR8-deficient mice are about 8% heavier than their wild-type age-matched controls after reaching 4 weeks of age. This weight difference is not caused by an altered food intake and is not exacerbated by feeding the animals a high-fat diet. Moreover, mGluR8 - / - mice are mildly insulin resistant, possibly as a result of being overweight. Behavioral testing revealed a reduced locomotor activity of mGluR8 - / - mice compared with wild-type mice during the first 3 days in a novel enclosed environment. However after 3 days, the locomotor activities of wild-type and mGluR8 - / - mice were similar, suggesting a reduced exploratory behavior of mGluR8 - / - mice in a novel enclosed environment. By contrast, there were no genotype differences in locomotor activity in the open field, plus maze, or in total time spent exploring objects during object recognition tests, indicating that there is a dissociation between effects of mGluR8 deficiency in exploratory activity in a novel safe enclosed environment vs. a more anxiogenic novel open environment. The absence of mGluR8 also leads to increased measures of anxiety in the open field and elevated plus maze. Whether the diverse phenotypic differences observed in mGluR8 - / - mice result from the misregulation of a unique neural pathway, possibly in the thalamus or hypothalamus, or whether they are the consequence of multiple developmental and functional alterations in synaptic transmission, remains to be determined.
93 citations
TL;DR: Common behavioural tests used to assess brain function are reviewed, and it is illustrated how behavioural tests are used to increase the understanding of the role of histaminergic neurotransmission in brain function.
Abstract: Molecular techniques allowing in vivo modulation of gene expression have provided unique opportunities and challenges for behavioural studies aimed at understanding the function of particular genes or biological systems under physiological or pathological conditions. Although various animal models are available, the laboratory mouse (Mus musculus) has unique features and is therefore a preferred animal model. The mouse shares a remarkable genetic resemblance and aspects of behaviour with humans. In this review, first we describe common mouse models for behavioural analyses. As both genetic and environmental factors influence behavioural performance and need to be carefully evaluated in behavioural experiments, considerations for designing and interpretations of these experiments are subsequently discussed. Finally, common behavioural tests used to assess brain function are reviewed, and it is illustrated how behavioural tests are used to increase our understanding of the role of histaminergic neurotransmission in brain function.
87 citations
TL;DR: It is shown that human apoE isoforms, which differ in AD risk, have differential effects on measures of anxiety in adult Apoe-/- male mice and male probable AD patients and PRAD patients with epsilon4/epsilon4 showed higher anxiety scores.
78 citations
TL;DR: It is shown that female tfm carrier mice outperform tfm male mice in the water maze, while there are no gender differences in water maze performance in wild-type mice, supporting a beneficial role for androgen receptors in spatial learning and memory.
42 citations
TL;DR: Androgens have differential roles in object recognition and spatial learning and memory in the water maze, depending on whether or not apoE4 is present, and castration did not modulate passive avoidance learning or memory.
42 citations
TL;DR: The effects of Histamine‐mediated signaling on anxiety and depression should be considered in assessments of the potential of histamine H3 receptor (H3R) ligands for conditions characterized by cognitive impairments as well as noncognitive behavioral impairments.
Abstract: Increasing evidence supports a role for histamine in anxiety and depression. In most studies, histamine and stimulation of the histamine H1 receptor (H1R) or blockade of the histamine H2 receptor (H2R) increase measures of anxiety. In contrast, in most studies histamine reduces depression-like activity, which might be related to effects of histamine on waking. These effects of histamine on anxiety and depression make histamine receptor ligands attractive therapeutic targets. As most studies assessing the potential of histamine receptor ligands on depression did not exclude potential effects of these ligands on locomotor activity, more studies are warranted to determine the exact role of histamine receptor subtypes in depression. The effects of histamine-mediated signaling on anxiety and depression should also be considered in assessments of the potential of histamine H3 receptor (H3R) ligands for conditions characterized by cognitive impairments as well as noncognitive behavioral impairments. Drug Dev. Res. 65:126–132, 2005. © 2005 Wiley-Liss, Inc.
9 citations