Neuronal
substrate of electrically induced grooming in
the PVH of the rat: involvement of oxytocinergic
systems?
AM. Von Erp, MR. Kruk, et al
Medical pharmacology,
Sylvius laboratory, U of Leiden,
Netherlands
Electrical stimulation of the hypothalamus
induces distinct behavioural responses.
Depending on the precise site of activation,
different responses are evoked: for example,
stimulation of the intermediate hypothalamic
area (MA), situated between the lateral
hypothalamus and ventromedial nucleus, may
induce attack behaviour, and stimulation of the
paraventricular area may induce self-grooming.
Depending on the current intensity used,
physical properties of the electrode, and
physiological properties of the brain tissue, a
larger or smaller population of neurons and/or
fibres may be activated. Therefore, a detailed
analysis of evoked behavioural responses has to
be combined with precise histological
verification, to identify the neuronal substrate
that is activated during elicitation of a
particular response. In the present report, the
hypothalamic distribution data from several
experiments, in which electrical stimulation was
used to evoke grooming responses, have been
pooled and their distribution reexamined. Some
of these data have been published
previously.
Grooming can also be induced by the
intracerebroventricular administration of
peptides, such as adrenocorticotrope hormone
(ACTH), a-melanocyte-stimulating hormone
(a-MSH), beta-endorphin, oxytocin, or bombesin.
In previous reports we have shown that local
injection of some of these peptides into or near
the PVH also may induce grooming. Interestingly,
we found that slow infusion of oxytocin into the
PVH in resting animals, after they had settled
down, induced grooming, whereas a-MSH had no
effect at all . This suggests that
oxytocin-receptive systems may be involved in
the initiation of grooming. It has been
described that, apart from the axons, the
dendrites of the oxytocinergic cells in the PVH
may release oxytocin as well. Therefore, we
decided to compare the distribution of electrode
sites at which grooming was induced with the
general distribution of oxytocin-immunoreactive
neurons and fibres in the PVH and rostral
hypothalamus. [...]
DISCUSSION
The distribution of electrode sites at which
grooming can be evoked with short latencies and
at low threshold current intensity is
concentrateil in the hypothalamic
paraventricular area. This area coincides with
previous observations. Moreover, it is very
similar to the area where grooming could be
elicited by microinjection of several
neuroactive substances. No grooming responses
can be evoked from other areas of the
hypothalamus, as bas been shown in an extensive
distribution study by Lammers et al.. The best
responses are consistently obtained from the PVH
(ie., for electrical stimulation: a threshold
for grooming within 10 s determined in the first
test; for peptide-induced grooming: grooming
within 1 min after injection, accompanied by
yawning and leading to a grooming score of more
that 70% in the first 15 min after injection).
In addition, grooming can be induced reliably
from areas adjacent to the PVH: around the
fornix, along the wall of the third ventricle,
and in the anterior hypothalamic area. In these
sites, grooming may be induced by activation of
afferent or efferent pathways to the PVH.
There are many different peptides present in
the PVH, of which several have been reported to
be involved in the regulation of grooming, such
as oxytocin, corticotropin-releasing hormone,
ACTH, and a-MSH. However, there are differences
in the grooming patterns induced by different
manipulations. Grootning induced by electrical
stimulation increases the frequency and duration
of face washing and body grooming, at the
expense of scratching. Grooming induced by
oxytocin infusion into the PVH of resting rats
also increases body groorning, but not face
washing, at the expense of tail and paw
grooming. Interestingly, we observed that at
sites in the PVH yawning was often induced,
after both electrical and mechanical
stimulation. Yawning has been reported to
occur after injection of oxytocin into the PVH.
Direct microinjections into the PVH of low doses
of excitatory amino acids (kainic acid, NMDA) or
peptides (ACTH, a-MSH) also induce grooming.
However, in a previous study we have shown that
grooming induced by peptides like ACTH and a-MSH
can be separated in two phases. The initiation
of grooming may be the result of mechanical
stimulation of the PVH and/or handling
procedures, because saline injections have a
similar effect. The administration of peptides
leads to a considerable prolongation of these
initial effects. Probably, the initiation phase
is an effect of tissue compression or damage in
or near the target area. This leads to the
release of endogenous substances from damaged
cells, which have an effect on neighbouring
cells. It is known that damaged cells release
large amounts of excitatory amino acids (EAAs).
This might lead to the activation of the area
surrounding the needle tip. Interestingly, slow
infusion into the PVH via a remote control
cannula system does not lead to a biphasic
grooming effect. In a resting animal, a-MSH
appears to be ineffective, whereas oxytocin
infusion induces a clear-cut grooming response.
This supports the suggestion that
oxytocinergic systems are involved in
PVH-induced grooming. Oxytocin infusions may
activate oxytocinergic neurons via putative
autoreceptors, whereas electrical stimulation
may activate oxytocinergic neurons and fibres
simultaneously.
In an extensive anatomical study, Roeling
showed that pathways originating from the
hypothalamic grooming area (HGA) are very
similar to the oxytocinergic pathways in the
brain, in contrast with projections from other
neighbouring parts of the hypothalamus. One of
the descending efferent pathways from the HGA
runs via the ventral tegmental area (VTA)
through the brainstem; another pathway runs via
the periaqueductal gray (PAG) and central
tegmental field. In a pilot study, we found that
PAG lesions, completely interrupting the
descending hypothalamic fibres, had no effect on
grooming responses evoked by electrical
stimulation of the HGA. This suggests that the
major pathway involved in hypothalamic grooming
runs ventrally via the VTA. Interestingly,
injection of oxytocin into the VTA has been
reported to induce grooming. Other findings
support the suggestion that the VTA, which is
one of the origins of the dopamine system, is
more important for the execution of hypothalamic
grooming than the opioid-rich PAG: the opiate
antagonist naloxone does not inhibit
electrically induced grooming, whereas the
dopaminergic antagonist haloperidol does (Van
Erp, unpublished data). Recently it has been
confirmed that the PAG is important for
ACTH-induced, but not oxytocin-induced,
grooming.
We conclude that there are interesting
similarities in the distribution of electrode
sites at which grooming can be induced and
oxytocinergic neurons and fibres in the
hypothalamus. Together with anatomical,
pharmacological, and lesion studies in and
outside the hypothalamus, we hypothesize that
electrical and mechanical stimulation of the
hypothalamic grooming area-including the PVH and
some closely surrounding parts of the rostral
hypothalamus- initiates a direct grooming
response, probably by involvement of
oxytocinergic mechanisms. However, more research
is needed to test this hypothesis (e.g., by
applying oxytocin antagonists during PVH
stimulation).
