Diet preferences as the cause of individual differences rather than the consequence.

Behavioural variation within a species is usually explained as the consequence of individual variation in physiology. However, new evidence suggests that the arrow of causality may well be in the reverse direction: behaviours such as diet preferences cause the differences in physiological and morphological traits. Recently, diet preferences were proposed to underlie consistent differences in digestive organ mass and movement patterns (patch residence times) in red knots (Calidris canutus islandica).

Understanding spatial distributions: negative density-dependence in prey causes predators to trade-off prey quantity with quality.

Negative density-dependence is generally studied within a single trophic level, thereby neglecting its effect on higher trophic levels. The 'functional response' couples a predator's intake rate to prey density. Most widespread is a type II functional response, where intake rate increases asymptotically with prey density; this predicts the highest predator densities at the highest prey densities.

In vitro and in vivo comparison of two non-peptide tachykinin NK3 receptor antagonists: Improvements in efficacy achieved through enhanced brain penetration or altered pharmacological characteristics.

Clinical evaluation of tachykinin NK(3) receptor antagonists has provided support for the therapeutic utility of this target in schizophrenia. However, these studies have not been entirely conclusive, possibly because of the pharmacokinetic limitations of these molecules. In the search for tachykinin NK(3) receptor antagonists with improved properties, we have discovered GSK172981 and GSK256471.

Increased expression of the NR2A NMDA receptor subunit in the prefrontal cortex of rats reared in isolation.

A hypofunction of the N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Compelling evidence of altered NMDA receptor subunit expression in the schizophrenic brain has not, however, so far emerged. Rats reared in isolation exhibit several characteristics, including disturbed sensory gating, which resemble those seen in schizophrenia.

Preclinical investigations into the antipsychotic potential of the novel histamine H3 receptor antagonist GSK207040.

Objectives: To test the novel nonimidazole histamine H3 receptor antagonist 5-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazapin-7-yl)oxy]-N-methyl-2-pyrazinecarboxamide (GSK207040) in a series of behavioral and neurochemical paradigms designed to evaluate its antipsychotic potential.

Materials And Methods: Acute orally administered GSK207040 was investigated for its capacity to reverse a 24-h-induced deficit in novel object recognition memory, deficits in prepulse inhibition (PPI) induced by isolation rearing, and hyperlocomotor activity induced by amphetamine. The acute neurochemical effects of GSK207040 were explored by analyzing rat anterior cingulate cortex microdialysates for levels of dopamine, noradrenaline, and acetylcholine and by c-fos immunohistochemistry.

In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): potential therapeutic utility in the treatment of schizophrenia.

Neurokinin-3 (NK3) receptors are concentrated in forebrain and basal ganglia structures within the mammalian CNS. This distribution, together with the modulatory influence of NK3 receptors on monoaminergic neurotransmission, has led to the hypothesis that NK3 receptor antagonists may have therapeutic efficacy in the treatment of psychiatric disorders. Here we describe the in vitro and in vivo characterization of the highly selective NK3 receptor antagonist talnetant (SB-223412).

Effect of the selective dopamine D3 receptor antagonist SB-277011-A on regional c-Fos-like expression in rat forebrain.

SB-277011-A is a dopamine D(3) receptor antagonist that exhibits over 100-fold selectivity over dopamine D(2) receptors and a broad spectrum of other receptor, ion channels, and enzymes. We employed c-Fos immunohistochemistry to characterise the functional neuroanatomical effects of acute administration of SB-277011-A and observed a time-dependent increase in the density of c-Fos-like positive nuclei in rat forebrain with maximal effects observed 2 h post-dose. The relative influence of the different brain regions on the overall effect of SB-277011-A was ranked by partial least squares discriminant analysis loadings plot which indicated that sites within the nucleus accumbens exerted the greatest influence on the separation of the vehicle and SB-277011-A treatment groups.

GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models.

6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) is a novel histamine H(3) receptor antagonist with high affinity for human (pK(i) = 9.59 -9.90) and rat (pK(i) = 8.

The effects of ziprasidone on regional c-Fos expression in the rat forebrain.

Rationale: Typical and atypical antipsychotic drugs produce characteristic patterns of immediate early gene expression in rat forebrain that are considered to reflect their effects in schizophrenia subjects.

Objective: To use c-Fos immunohistochemistry to investigate the functional neuroanatomical profile of the newly introduced atypical agent ziprasidone.

Materials And Methods: c-Fos immunohistochemistry was performed on paraformaldehyde-fixed cryosections of rat brains obtained, initially, from animals 2, 4, or 6 h after oral administration of 10 mg/kg ziprasidone or vehicle and, subsequently, from animals 2 h after oral administration of 1, 3, or 10 mg/kg ziprasidone or vehicle.

LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric disease.

Several psychiatric diseases, including schizophrenia, are thought to have a developmental aetiology, but to date no clear link has been made between psychiatric disease and a specific developmental process. LPA(1) is a G(i)-coupled seven transmembrane receptor with high affinity for lysophosphatidic acid. Although LPA(1) is expressed in several peripheral tissues, in the nervous system it shows relatively restricted temporal expression to neuroepithelia during CNS development and to myelinating glia in the adult.

Protein distribution of the orexin-2 receptor in the rat central nervous system.

Orexin-A and -B are neuropeptides mainly expressed in the lateral hypothalamic area (LHA). A role for orexins was first demonstrated in the regulation of feeding behaviour. Subsequently, the peptides have been implicated in the control of arousal.

Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS.

TREK-1 is a member of the two-pore-domain potassium channel family which is expressed predominantly in the CNS. Using an anti-peptide polyclonal antiserum, we have determined the distribution of TREK-1 in the brain and spinal cord of adult rats. Specificity of the antiserum was tested using a TREK-1-transfected cell line and confirmed with c-myc-tagged TREK-1.

Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord.

Orexins-A and -B are neuropeptides derived from a single precursor prepro-orexin. The mature peptides are mainly expressed in the lateral hypothalamic and perifornical areas. The orexins have been implicated in the control of arousal and appear to be important messengers in the regulation of food intake.

Expression of melanin-concentrating hormone receptors in insulin-producing cells: MCH stimulates insulin release in RINm5F and CRI-G1 cell-lines.

Melanin-concentrating hormone (MCH) is a hypothalamic orexigenic peptide. Recently, an orphan G-protein-coupled receptor (SLC-1) was identified that binds MCH with high affinity. Here, we demonstrate the mRNA expression of this receptor in insulin-producing cells including CRI-G1 and RINm5F cells, and in rat islets of Langerhans.

The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat.

Melanin-concentrating hormone (MCH), a 19 amino acid cyclic peptide, is largely expressed in the hypothalamus. It is implicated in the control of general arousal and goal-orientated behaviours in mammals, and appears to be a key messenger in the regulation of food intake. An understanding of the biological actions of MCH has been so far hampered by the lack of information about its receptor(s) and their location in the brain.

Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1.

The underlying causes of obesity are poorly understood but probably involve complex interactions between many neurotransmitter and neuropeptide systems involved in the regulation of food intake and energy balance. Three pieces of evidence indicate that the neuropeptide melanin-concentrating hormone (MCH) is an important component of this system. First, MCH stimulates feeding when injected directly into rat brains; second, the messenger RNA for the MCH precursor is upregulated in the hypothalamus of genetically obese mice and in fasted animals; and third, mice lacking MCH eat less and are lean.