Periaqueductal
gray lesions do not affect grooming, induced
electrically in the hypothalamic paraventricular
area in the rat
AM Van Erp, MR Kruk, W Meelis, JG
Veening
Ethopharmacology Group,
Sylvius Laboratory, University of
Leiden,
Department of Anatomy and
Embryology, University of Nijrnegen,
The Netherlands
Introduction : Electrical stimulation
of specific areas in the hypothalamus evokes
complex behavioural patterns. Depending on the
exact location of the electrode, different
responses are evoked, such as attack behaviour
or self-grooming. Self-grooming can be evoked in
the paraventricular nucleus (PVH) and dorsal
hypothalamic area (DHA). Several descending and
ascending pathways have been described that may
be involved in the execution of these
behavioural responses. One particular pathway
runs from the hypothalamus through the
periaqueductal gray area (PAG) and the adjoining
parts of the brain stem. The PAG seems to be
involved in aggressive and defensive behaviour
and has been shown to be crucial for
ACTH-induced grooming. However, Mos et al showed
that PAG lesions only slightly and transiently
reduce aggression evoked by hypothalamic
stimulation and aggression in a territorial
setting (resident/intruder paradigm). Therefore,
it seemed worthwhile to investigate the effect
of PAG lesions on hypothalamically induced
grooming behaviour, to study the role of the PAG
in the execution of self-grooming.
[...]
Discussion : Our study shows that
lesions of the periaqueductal gray area have no
effect on thresholds for hypothalamically evoked
self-grooming behaviour. This is in line with
the effect of PAG lesions on hypothalamic attack
responses. Mos et al showed that PAG lesions
only slightly and transiently reduce thresholds
for hypothalamic attack. In general,
hypothalamic responses may consist of either
changes in the introductory phase of behaviour,
e.g. after ventromedial hypothalamic stimulation
or consist of a clearcut response, often of a
compulsive nature, e.g. attack or grooming
responses. Animals interrupt ongoing behaviour
immediately and show the particular response
elicited within seconds after onset of
stimulation. Behaviourally it seems that a
system involved in the execution phase of the
behaviour, rather than the introductory or
decision making phase, is activated.
Which pathways are involved in these
hypothalamic responses? Fibres descend towards
the lower parts of the brainstem either via the
ventral tegmental area and the central tegmental
field, or along the midline via the PAG. In
addition, ascending fibres and fibres with a
thalamic destination may play a role, as well as
other ascending projections to the forebrain.
Interestingly, hypothalamic projections to the
PAG show a topographical and the fibres
originating from the hypothalamic attack area
(caudal, lateral PAG) show a distribution that
is very different from fibres originating from
the hypothalamic grooming area (dorsal and
lateral PAG).
Spruijt et al showed that the PAG is a
prerequisite for ACTHinduced grooming. PAG
lesions diminished the response to i.c.v.
injections of ACTH 1-21. However, grooming did
not disappear completely, but was reduced to
baseline level. There are several possible
explanations for these seemingly contradictory
results. Recent experiments, in which grooming
was induced by direct injection of neuropeptides
into the PVH suggest that peptides such as ACTH
and alpha-MSH prolong a grooming response that
was initiated by other factors, e.g. handling of
the rat or exposure to a novel environment. In
contrast, a peptide such as oxytocin seems to
initiate grooming. Apparently, separate
systems exist in the central nervous system that
regulate the initiation of groorning, its
continuation and probably the interruption of
this behaviour. We hypothesise that ACTH,
for which binding sites are present in the PAG
serves to modulate grooming that has been
initiated by other factors outside the PAG. This
could explain the fact that after PAG lesions
grooming is still performed at baseline level.
The modulatory effect of the PAG on grooming has
been confirmed recently by Van Wimersma
Greidanus, who showed that PAG lesions attenuate
ACTH- but not oxytocin-induced grooming.
Nevertheless, our results suggest that the PAG
is not the major destination station involved in
hypothalamically evoked grooming responses.
A recent study by Roeling showed that one of
the many efferent pathways originating from the
PVH that is possibly involved in the execution
of grooming, is the connection descending via
lateral hypothalamus, ventral tegmental area
(VTA) and central tegmental field.
Interestingly, the VTA is one of the areas of
the brain that has been reported to be involved
in grooming behaviour: injection of
neuropeptides, such as oxytocin, CCK and
alpha-MSH into the VTA induces selfgrooming
behaviour. The possible involvement of the VTA
in the control of hypothalamic responses
deserves special attention in future studies,
although a similar study using VTA lesions may
prove difficult to perform because of severe
effects on autonomic functions.
Lesions of the periaqueductal gray resulted
in severe behavioural deficits. Some of these
effects inay have been caused by lesions of
tissue surrounding the PAG, especially in
animals with large lesions in which ascending
serotonergic and/or noradrenergic pathways may
have been disrupted. Animals didn't eat or drink
(also reported by Mos et al): they seemed to
have -forgotten- how to do it, because they
would drink readily when helped and showed
interest in wet mesh after they had been
drinking. It is interesting to not that several
animals showed moderate to strong defensive
reactions upon touch, despite the intensive
handling period before surgery. They didn't try
to bite, but upon touch by the experimenters
hand tried to escape by running and jumping and
sometimes they screamed when picked up. This
observation is at odds with reports that PAG
lesions attenuate defensive behaviour for which
we have no explanation. Others have reported
that PAG lesions do not change defensive
reactions induced by other means either, e.g.
inferior colliculus stimulation.
In addition, some animals showed reflex-like
face washing movements upon stimulation of the
mouth region with a wet syringe during drinking
sessions. These movements were quite strong and
compulsive, performed in a position in which a
rat normally would never groom (restrained,
lying on its back). These movements were not
just attempts to remove the syringe, but
included the repetitive "front paw over car"
movements that arc characteristic for face
washing. This is an important observation,
showing that the animals are still responding to
sensory stimuli. Apparently the sensory input
pathways are intact, as well as the motor
components of the grooming behaviour. In spite
of the fact that they have a problem in
maintaining their body posture, they still
groom, even while lying on their back. We could
not correlate the nature of observed behavioural
deficits (defensive behaviour, face washing upon
stimulation of mouth region) to the size or
extension of the lesions. These clear deficits,
however, did not affect the hypothalamically
evoked grooming response, neither inhibitory nor
facilitatory.
