|
Current Neuropharmacology
ISSN: 1570-159X
Current Neuropharmacology
Volume 4, Number 4, October 2006
Contents
Aminergic Control and Modulation of Honeybee Behaviour
Pp. 259-276
R. Scheiner, A. Baumann and W. Blenau
[Abstract]
Neurochemistry of the Nucleus Accumbens and its
Relevance to Depression and Antidepressant Action in Rodents
Pp. 277-291
Y. Shirayama and S. Chaki
[Abstract]
Molecular Mechanisms, Biological Actions, and
Neuropharmacology of the Growth-Associated Protein GAP-43
Pp. 293-304
J.B. Denny
[Abstract]
L-Glutamate and its Ionotropic Receptors in the
Nervous System of Cephalopods Pp. 305-312
A. Di Cosmo, C. Di Cristo and J.B. Messenger
[Abstract]
The Pharmacology of the Neurochemical Transmission
in the Midbrain Raphe Nuclei of the Rat Pp. 313-339
L.G. Harsing
[Abstract]
Abstracts
[Back to top]
Aminergic Control and Modulation of Honeybee Behaviour
R. Scheiner, A. Baumann and W. Blenau
Biogenic amines are important messenger substances in the
central nervous system and in peripheral organs of vertebrates
and of invertebrates. The honeybee, Apis mellifera,
is excellently suited to uncover the functions of biogenic
amines in behaviour, because it has an extensive behavioural
repertoire, with a number of biogenic amine receptors characterised
in this insect.
In the honeybee, the biogenic amines dopamine, octopamine,
serotonin and tyramine modulate neuronal functions in various
ways. Dopamine and serotonin are present in high concentrations
in the bee brain, whereas octopamine and tyramine are less
abundant. Octopamine is a key molecule for the control of
honeybee behaviour. It generally has an arousing effect and
leads to higher sensitivity for sensory inputs, better learning
performance and increased foraging behaviour. Tyramine has
been suggested to act antagonistically to octopamine, but
only few experimental data are available for this amine. Dopamine
and serotonin often have antagonistic or inhibitory effects
as compared to octopamine.
Biogenic amines bind to membrane receptors that primarily
belong to the large gene-family of GTP-binding (G) protein
coupled receptors. Receptor activation leads to transient
changes in concentrations of intracellular second messengers
such as cAMP, IP3 and/or Ca2+. Although
several biogenic amine receptors from the honeybee have been
cloned and characterised more recently, many genes still remain
to be identified. The availability of the completely sequenced
genome of Apis mellifera will contribute
substantially to closing this gap.
In this review, we will discuss the present knowledge on how
biogenic amines and their receptor-mediated cellular responses
modulate different behaviours of honeybees including learning
processes and division of labour.
[Back to top]
Neurochemistry of the Nucleus Accumbens and its
Relevance to Depression and Antidepressant Action in Rodents
Y. Shirayama and S. Chaki
There is accumulating evidence that the nucleus accumbens
(NAc) plays an important role in the pathophysiology of depression.
Given that clinical depression is marked by anhedonia (diminished
interest or pleasure), dysfunction of the brain reward pathway
has been suggested as contributing to the pathophysiology
of depression.
Since the NAc is the center of reward and learning, it is
hypothesized that anhedonia might be produced by hampering
the function of the NAc. Indeed, it has been reported that
stress, drug exposure and drug withdrawal, all of which produce
a depressive-phenotype, alter various functions within the
NAc, leading to inhibited dopaminergic activity in the NAc.
In this review, we describe various factors as possible candidates
within the NAc for the initiation of depressive symptoms.
First, we discuss the roles of several neurotransmitters and
neuropeptides in the functioning of the NAc, including dopamine,
glutamate, γ-aminobutyric
acid (GABA), acetylcholine, serotonin, dynorphin, enkephaline,
brain-derived neurotrophic factor (BDNF), cAMP response element-binding
protein (CREB), melanin-concentrating hormone (MCH) and cocaine-
and amphetamine-regulated transcript (CART). Second, based
on previous studies, we propose hypothetical relationships
among these substances and the shell and core subregions of
the NAc.
[Back to top]
Molecular Mechanisms, Biological Actions, and
Neuropharmacology of the Growth-Associated Protein GAP-43
J.B. Denny
GAP-43 is an intracellular growth-associated protein that
appears to assist neuronal pathfinding and branching during
development and regeneration, and may contribute to presynaptic
membrane changes in the adult, leading to the phenomena of
neurotransmitter release, endocytosis and synaptic vesicle
recycling, long-term potentiation, spatial memory formation,
and learning. GAP-43 becomes bound via palmitoylation
and the presence of three basic residues to membranes of the
early secretory pathway. It is then sorted onto vesicles at
the late secretory pathway for fast axonal transport to the
growth cone or presynaptic plasma membrane. The palmitate
chains do not serve as permanent membrane anchors for GAP-43,
because at steady-state most of the GAP-43 in a cell is membrane-bound
but is not palmitoylated. Filopodial extension and branching
take place when GAP-43 is phosphorylated at Ser-41 by protein
kinase C, and this occurs following neurotrophin binding and
the activation of numerous small GTPases. GAP-43 has been
proposed to cluster the acidic phospholipid phosphatidylinositol
4,5-bisphosphate in plasma membrane rafts. Following GAP-43
phosphorylation, this phospholipid is released to promote
local actin filament-membrane attachment. The phosphorylation
also releases GAP-43 from calmodulin. The released GAP-43
may then act as a lateral stabilizer of actin filaments. N-terminal
fragments of GAP-43, containing 10-20 amino acids, will activate
heterotrimeric G proteins, direct GAP-43 to the membrane and
lipid rafts, and cause the formation of filopodia, possibly
by causing a change in membrane tension. This review will
focus on new information regarding GAP-43, including its binding
to membranes and its incorporation into lipid rafts, its mechanism
of action, and how it affects and is affected by extracellular
agents.
[Back to top]
L-Glutamate and its Ionotropic Receptors in the
Nervous System of Cephalopods
A. Di Cosmo, C. Di Cristo and J.B. Messenger
In several species of cephalopod molluscs there is good evidence
for the presence of L-glutamate in the central and peripheral
nervous system and evidence for both classes of ionotropic
receptor, AMPA/kainate and NMDA.
The best evidence for glutamate being a transmitter in cephalopods
comes from pharmacological, immunohistochemical and molecular
investigations on the giant fibre system in the squid stellate
ganglion. These studies confirm there are AMPA/kainate-like
receptors on the third-order giant axon. In the (glial) Schwann
cells associated with the giant axons both classes of glutamate
receptor occur.
Glutamate is an excitatory transmitter in the chromatophores
and in certain somatic muscles and its action is mediated
primarily via AMPA/kainate-like receptors, but at
some chromatophores there are NMDA-like receptors.
In the statocysts the afferent crista fibres are also glutamatergic,
acting at non-NMDA receptors.
In the brain (of Sepia) a neuronal NOS is activated
by glutamate with subsequent production of nitric oxide and
elevation of cGMP levels. This signal transduction pathway
is blocked by D-AP-5, a specific antagonist of the NMDA receptor.
Recently immunohistochemical analysis has demonstrated (in
Sepia and Octopus) the presence of NMDAR2A
/B – like receptors in motor centres, in the visual
and olfactory systems and in the learning system. Physiological
experiments have shown that glutamatergic transmission is
involved in long term potentation (LTP) in the vertical lobe
of Octopus, a brain area involved in learning. This
effect seems to be mediated by non-NMDA receptors. Finally
in the CNS of Sepia NMDA-mediated nitration of tyrosine
residues of cytoskeletal protein such as a-tubulin, has been
demonstrated.
[Back to top]
The Pharmacology of the Neurochemical Transmission
in the Midbrain Raphe Nuclei of the Rat
L.G. Harsing
Midbrain slices containing the dorsal and medial raphe nuclei
were prepared from rat brain, loaded with [3H]serotonin
([3H]5-HT), superfused and the release of [3H]5-HT
was determined at rest and in response to electrical stimulation.
Compartmental analysis of [3H]5-HT taken up by
raphe tissue indicated various pools where the neurotransmitter
release may originate from these stores differed both in size
and rate constant. 5-HT release originates not only from vesicles
but also from cytoplasmic stores via a transporter-dependent
exchange process establishing synaptic and non-synaptic neurochemical
transmission in the serotonergic somatodendritic area. Manipulation
of 5-HT transporter function modulates extracellular 5-HT
concentrations in the raphe nuclei: of the SSRIs, fluoxetine
was found 5-HT releaser, whereas citalopram did not exhibit
this effect. Serotonergic projection neurons in the raphe
nuclei possess inhibitory 5-HT1A and 5-HT1B/1D
receptors and facilitatory 5-HT3 receptors, which
regulate 5-HT release in an opposing fashion. This observation
indicates that somatodendritic 5-HT release in the raphe nuclei
is under the control of several 5-HT homoreceptors. 5-HT7
receptors located on glutamatergic axon terminals indirectly
inhibit 5-HT release by reducing glutamatergic facilitation
of serotonergic projection neurons. An opposite regulation
of glutamatergic axon terminals was also found by involvement
of the inhibitory 5-HT7 and the stimulatory 5-HT2
receptors as these receptors inhibit and stimulate glutamate
release in raphe slice preparation, respectively, Furthermore,
postsynaptic 5-HT1B/1D heteroreceptors interact
with release of GABA in inhibitory fashion in raphe GABAergic
interneurons. Serotonergic projection neurons also possess
glutamate and GABA heteroreceptors; NMDA and AMPA receptors
release 5-HT, whereas both GABAA and GABAB
receptors inhibit somatodendritic 5-HT release. Evidence was
found for reciprocal interactions between serotonergic and
glutamatergic as well as serotonergic and GABAergic innervations
in the raphe nuclei. Serotonergic neurons in the raphe nuclei
also receive noradrenergic innervation arising from the locus
coeruleus and alpha-1 and alpha-2 adrenoceptors inhibited
[3H]5-HT release in our experimental conditions.
The close relation between 5-HT transporter and release-mediating
5-HT autoreceptors was also shown by addition of L-deprenyl,
a drug possessing inhibition of type B monoamine oxidase and
5-HT reuptake. L-Deprenyl selectively desensitizes 5-HT1B
but not 5-HT1A receptors and these effects are
not related to inhibition of 5-HT metabolism but rather to
inhibition of 5-HT transporter.
|
