Prevalence and symptomatology of depression in older people living in institutions in England and Wales.

Background: Epidemiological studies have shown that depression is common in institutional settings. However, the symptomatology of depression in this group has not been compared to those living in the community.

Aims: To estimate the prevalence of depression and depressive symptomatology in participants living in institutions and compare these to people living in other settings.

5-Bromo-2'-deoxyuridine is selectively toxic to neuronal precursors in vitro.

The effect of 5-bromo-2'-deoxyuridine (BrdU) incorporation on the phenotype of progeny derived from expanded E18 rat striatal precursors was examined. BrdU was administered to cultures for 24 h prior to differentiation. Results revealed that there was selective toxicity of this compound to developing TuJ1+ neurons, but not glia, at concentrations used in most labelling studies.

Heparin stabilizes FGF-2 and modulates striatal precursor cell behavior in response to EGF.

Fibroblast and epidermal growth factors (FGF-2 and EGF) are powerful mitogens for neural precursor cells isolated from the developing striatum and grown as neurospheres. However, questions remain as to the exact role of each of these molecules, and how the proteoglycan heparin may modify their behavior. Here, we show that FGF-2 is remarkably unstable in culture media, but that heparin could completely prevent its degradation, which led to faster cell growth rates.

Identification of MEK1 as a novel target for the treatment of neuropathic pain.

(1) In the present study we have attempted to identify changes in gene expression which are associated with neuropathic pain using subtractive suppression hybridization analysis of the lumbar spinal cord of animals suffering streptozocin induced diabetic neuropathy. (2) Using this approach, we found a significant up-regulation of several key components of the extracellular signal-regulated kinase (ERK) cascade. These findings were confirmed by Western blot analysis, which demonstrated that the levels of active ERK1 and 2 correlated with the onset of streptozocin-induced hyperalgesia.

Serotonin receptor mRNA expression in rat dorsal root ganglion neurons.

In the present study, we have used in situ hybridization to examine the distribution of serotonin (5-HT) receptors in rat dorsal root ganglion (DRG) neurons. Within DRG neurons, mRNAs for 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT3B and 5-HT4 receptors were readily detected in small (<25 microm), medium (25-45 microm) and large (>45 microm) diameter neurons. In contrast mRNAs for 5-HT1A, 5-HT1E, 5-HT2C, 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7 receptors were undetectable in these neurons.

Functional and molecular characterization of metabotropic glutamate receptors expressed in rat striatal cholinergic interneurones.

In the present study we have used single-cell RT-PCR in conjunction with electrophysiology to examine the expression and functional properties of metabotropic glutamate receptors (mGluRs) expressed within biochemically identified cholinergic interneurones in the rat striatum. Using single-cell RT-PCR, it was possible to demonstrate the presence of mGluR1, mGluR2, mGluR3, mGluR5 and mGluR7 mRNAs within single cholinergic interneurones. Bath application of the non-selective mGluR agonist (1 S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1 S,3R-ACPD) or the group-I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) depolarized all cholinergic neurones tested by activation of an inward current at -60 mV.

In vitro characterization of Ac-RYYRWK-NH(2), Ac-RYYRIK-NH(2) and [Phe1Psi(CH(2)-NH)Gly2] nociceptin(1-13)NH(2) at rat native and recombinant ORL(1) receptors.

The pharmacology of ORL(1) compounds, [Phe1Psi(CH(2)-NH)Gly2]nociceptin(1-13)NH(2) (F/GNC13), Ac-RYYRIK-NH(2) and Ac-RYYRWK-NH(2) was evaluated at rat ORL(1) receptors in frontal cortex (CTX), transfected chinese hamster ovary (CHO) cells, vas deferens (VD) and anococcygeus (AC). Ranked affinities for the inhibition of [3H]nociceptin binding to CTX and CHO's were: Ac-RYYRWK-NH(2) identical withAc-RYYRIK-NH(2) identical withnociceptin>F/GNC13>Dynorphin A>naloxone. The full agonist, nociceptin stimulated [35S]GTPgammaS binding in CTX (E(max)=174%) and CHO's (E(max)=311%); all other ORL(1) peptides acted as partial agonists with the following rank order for E(max) values: Ac-RYYRWK-NH(2) (96% (CTX), 202% (CHO))>F/GNC13 (44% (CTX), 136% (CHO)) identical withAc-RYYRIK-NH(2) (44% (CTX), 115% (CHO)).

Identification and characterisation of functional bombesin receptors in human astrocytes.

Reverse transcription polymerase chain reaction (RT-PCR) demonstrated the presence of bombesin BB2 receptor mRNA but not bombesin BB1 receptor or bombesin BB3 receptor mRNA in cultured human astrocytes. Neuromedin C hyperpolarised human astrocytes in whole-cell current and voltage clamp recordings and increased the intracellular free Ca(2+) ion concentration ([Ca(2+)](i)) in single astrocytes. Treatment with neuromedin C caused larger and more frequent increases in [Ca(2+)](i) than those triggered by neuromedin B, with 96% and 78% of cells responding, respectively.

Activation of astrocyte intracellular signaling pathways by interleukin-1 in rat primary striatal cultures.

The striatum has been implicated as the site of action mediating neurotoxic effects of interleukin-1 (IL-1) during ischemia. However, the molecular mechanisms underlying these events have yet to be fully addressed. In the present study, primary cultures of rat striatal cells were used as a model for the study of IL-1 signaling pathways in the striatum.

Adenosine exerts multiple effects in dorsal horn neurones of the adult rat spinal cord.

In the present study, we have examined the effects of adenosine and its analogues on the electrophysiological properties of dorsal horn neurones in the rat adult spinal cord. Adenosine and the A1 receptor agonist R-phenylisopropyl adenosine (RPIA) reversibly hyperpolarised these neurones via the generation of an outward current at -60 mV that was inhibited by pre-application of barium or Rp-adenosine 3', 5'-cyclic monophosphothioate triethylamine. In contrast, the A2a receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) had no effect on the resting membrane properties of these neurones.

Streptozocin-induced neuropathy is associated with altered expression of voltage-gated calcium channel subunit mRNAs in rat dorsal root ganglion neurones.

Voltage-gated calcium channels (VGCCs) within sensory neurones are believed to perform an important role in neuropathic pain. In the present study we examine the changes in VGCC mRNA which occur following streptozocin- (STZ) induced diabetic neuropathy using in situ hybridization. STZ caused a significant increase in alpha(2)delta(1), alpha(2)delta(2), and alpha(2)delta(3) mRNA levels in all neuronal cell types.

Expression of voltage-gated calcium channel subunits in rat dorsal root ganglion neurons.

In the present study, we have used in situ hybridisation to examine the distribution of calcium channel subunits in rat dorsal root ganglion (DRG) neurons. Within DRG neurons, the calcium channel alpha subunit mRNAs alpha(1A), alpha(1B), alpha(1C), alpha(1D), alpha(1E), alpha(1I) and alpha(1S) were readily detected in small (<25 microm), medium (25-45 microm) and large (>45 microm) diameter neurons. alpha(1F) was present at very low levels in these neurons whilst alpha(1G) was virtually undetectable.

Beta3, a novel auxiliary subunit for the voltage gated sodium channel is upregulated in sensory neurones following streptozocin induced diabetic neuropathy in rat.

In the present study we have used in situ hybridization to examine the changes in mRNA expression of the voltage gated sodium channel subunits beta1 and beta3, which occur in response to streptozocin induced diabetic neuropathy. Under control conditions beta1 mRNA was detected throughout the spinal cord and in large dorsal root ganglion (DRG) Abeta fibres whilst beta3 mRNA was expressed exclusively in the layers I/II and X of the spinal cord and in small DRG c-fibres. Following streptozocin treatment, the expression of beta1 mRNA remained unchanged in both the spinal cord and DRG whilst beta3 message was significantly increased in both the spinal cord and in medium diameter Adelta type DRG neurones.

Developmental expression of the novel voltage-gated sodium channel auxiliary subunit beta3, in rat CNS.

1. We have compared the mRNA distribution of sodium channel alpha subunits known to be expressed during development with the known auxiliary subunits Nabeta1.1 and Nabeta2.

Utilization of an intramolecular hydrogen bond to increase the CNS penetration of an NK(1) receptor antagonist.

This paper describes the synthesis and physical and biological effects of introducing different substituents at the alpha-position of the tryptophan containing neurokinin-1 receptor antagonist [(R)-2-(1H-indol-3-yl)-1-methyl-1-((S)-1-phenyl-ethylcarbamoyl)-ethyl]-carbamic acid benzofuran-2-ylmethyl ester (CI 1021). The described compounds all exhibit less than 5 nM binding affinities for the human neurokinin-1 receptor and selectivity over the tachykinin NK(2) and NK(3) receptor subtypes. Application of variable temperature nuclear magnetic resonance spectroscopy studies of the amide and urethane protons was utilized to determine the existence of an intramolecular hydrogen bond.

Gabapentin inhibits the substance P-facilitated K(+)-evoked release of [(3)H]glutamate from rat caudial trigeminal nucleus slices.

The effect of gabapentin on the release of the spinal sensory neurotransmitter glutamate has been investigated in an in vitro model using a perfused thin slice preparation from the rat brainstem containing the spinal trigeminal caudal subnucleus (Sp5C) and pre-incubated with [(3)H]glutamate. Addition of excess K(+) to the perfusing solution increased the content of tritium in the perfusate. The prior addition of substance P increased this index of glutamate release in a concentration-dependent manner, with the mean maximum of around 50% increase obtained at 1-3 microM.

Ovariohysterectomy in the rat: a model of surgical pain for evaluation of pre-emptive analgesia?

Ovariohysterectomy in the rat led to the induction of abdominal postures and referred mechanical allodynia in the hind paws. The latter was differentiated into static and dynamic subtypes. The abdominal postures were present up to 4-5 h, whilst the two types of allodynia lasted for at least 2 days.

Histamine depolarizes cholinergic interneurones in the rat striatum via a H(1)-receptor mediated action.

1. Whole-cell patch clamp recordings were made from rat striatal cholinergic interneurones in slices of brain tissue in vitro. Bath application of histamine (EC(50) 6.

beta3, a novel auxiliary subunit for the voltage-gated sodium channel, is expressed preferentially in sensory neurons and is upregulated in the chronic constriction injury model of neuropathic pain.

Adult dorsal root ganglia (DRG) have been shown to express a wide range of voltage-gated sodium channel alpha-subunits. However, of the auxiliary subunits, beta1 is expressed preferentially in only large- and medium-diameter neurons of the DRG while beta2 is absent in all DRG cells. In view of this, we have compared the distribution of beta1 in rat DRG and spinal cord with a novel, recently cloned beta1-like subunit, beta3.

Characterization of the ORL(1) receptor on adrenergic nerves in the rat anococcygeus muscle.

1. Nociceptin, the endogenous ORL(1) receptor agonist inhibited the motor response to electrical-field stimulation in the rat anococcygeus muscle. This effect was characterized using the peptide ligands acetyl-Arg-Tyr-Tyr-Arg-Trp-Lys-NH(2) (Ac-RYYRWK-NH(2)), acetyl-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)) and [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin(1-13)NH(2) ([F/G]NC(1-13)NH(2)), and the non-selective opioid antagonist naloxone benzoylhydrazone (NalBzOH).

Further evidence for the role of the alpha(2)delta subunit of voltage dependent calcium channels in models of neuropathic pain.

1. Current analgesic therapy is dominated by NSAIDs and opiates, however these agents have limited efficacy in the treatment of neuropathic pain. The novel anticonvulsant agent gabapentin (Neurontin) has been shown to be an effective treatment for neuropathic pain in the clinic.

Gabapentin inhibits excitatory synaptic transmission in the hyperalgesic spinal cord.

In the present study we tested the effects of the antihyperalgesic compound gabapentin on dorsal horn neurones in adult spinal cord. Slices were taken from control and hyperalgesic animals suffering from streptozocin-induced diabetic neuropathy. At concentrations up to 100 microM, bath application failed to affect the resting membrane properties of dorsal horn neurones taken from both groups of animal.

Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain.

CI-1021 ([(2-benzofuran)-CH(2)OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH (3))Ph) is a selective and competitive neurokinin-1 (NK(1)) receptor antagonist. This study examines its activity in animal models of inflammatory and neuropathic pain. In mice, CI-1021 (1-30 mg/kg, s.

NK-3 receptors are expressed on mouse striatal gamma-aminobutyric acid-ergic interneurones and evoke [(3)H] gamma-aminobutyric acid release.

In the present study the ability of tachykinin agonists and antagonists to modulate gamma-aminobutyric acid (GABA) release has been correlated with tachykinin receptor expression in the mouse striatum. Significant GABA release was observed when striatal slices were challenged with the NK-3 receptor agonist senktide, the selectivity of which was confirmed using the NK-3 receptor antagonist SR142801. In situ hybridisation revealed co-expression of NK-3 receptors with nitric oxide synthase (NOS)/preprosomatostatin containing GABAergic interneurones.

Effect of gastrin-releasing peptide on rat hippocampal extracellular GABA levels and seizures in the audiogenic seizure-prone DBA/2 mouse.

Gastrin-releasing peptide (GRP), a selective agonist for the BB(2) subtype of bombesin receptor, is reported to depolarise GABAergic interneurons in the stratum oriens layer of the hippocampus. Such an action might lead to increased extracellular levels of GABA in the hippocampus, and result in an anti-convulsant effect with this peptide. We have tested this hypothesis by determining the effect of GRP on extracellular levels of GABA in the ventral hippocampus of the freely moving rat using in vivo microdialysis, and by intracerebroventricular (i.